AIM： To investigate the relationship between the -765G 〉 C COX-2 polymorphism and the development of different gastric lesions： atrophy or intestinal metaplasia and gastric adenocarcinoma. METHODS： A cross-section...AIM： To investigate the relationship between the -765G 〉 C COX-2 polymorphism and the development of different gastric lesions： atrophy or intestinal metaplasia and gastric adenocarcinoma. METHODS： A cross-sectional study was performed involving 320 Portuguese individuals （210 without evidence of neoplastic disease, 73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal metaplasia） using a PCR-RFLP method.RESULTS： -765C allele was overrepresented in the patients with gastric adenocarcinoma （51%） when compared either with the control group （38%） or patients with atrophy or intestinal metaplasia （27%）. Callele was found to be very common in our population （0.22）, and a multivariate logistic regression analysis revealed nearly 3-fold increased risk for the progression to gastric adenocarcinoma in patients with atrophy or intestinal metaplasia carrying the -765C allele （OR = 2.67, 95% CI = 1.03-6.93; P = 0.04）.CONCLUSION： -765C carrier status should be considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.展开更多
Interleukin-6(IL-6)is a pleiotropic cytokine involved in prostate regulation and in prostate cancer(PC)development/progression.IL-6 acts as a paracrine and autocrine growth stimulator in benign and tumor prostate cell...Interleukin-6(IL-6)is a pleiotropic cytokine involved in prostate regulation and in prostate cancer(PC)development/progression.IL-6 acts as a paracrine and autocrine growth stimulator in benign and tumor prostate cells.The levels of IL-6 and respective receptors are increased during prostate carcinogenesis and tumor progression.Several studies reported that increased serum and plasma IL-6 and soluble interleukin-6 receptor levels are associated with aggressiveness of the disease and are associated with a poor prognosis in PC patients.In PC treatment,patients diagnosed with advanced stages are frequently submitted to hormonal castration,although most patients will eventually fail this therapy and die from recurrent castration-resistant prostate cancer(CRPC).Therefore,it is important to understand the mechanisms involved in CRPC.Several pathways have been proposed to be involved in CRPC development,and their understanding will improve the way to more effective therapies.In fact,the prostate is known to be dependent,not exclusively,on androgens,but also on growth factors and cytokines.The signaling pathway mediated by IL-6 may be an alternative pathway in the CRPC phenotype acquisition and cancer progression,under androgen deprivation conditions.The principal goal of this review is to evaluate the role of IL-6 pathway signaling in human PC development and progression and discuss the interaction of this pathway with the androgen recepto pathway.Furthermore,we intend to evaluate the inclusion of IL-6 and its receptor levels as a putative new class of tumor biomarkers.The IL-6/IL-6R signaling pathway may be included as a putative molecular marker for aggressiveness in PC and it may be able to maintain tumor growth through the AR pathway under androgen-deprivation conditions.The importance of the IL-6/IL-6R pathway in regulation of PC cells makes it a good candidate for targeted therapy.展开更多
AIM： To study the role of an insertion/deletion polymorphism in the pepsinogen C （PGC） gene, an effective marker for terminal differentiation of the stomach mucosa, in the susceptibility to the development of gastr...AIM： To study the role of an insertion/deletion polymorphism in the pepsinogen C （PGC） gene, an effective marker for terminal differentiation of the stomach mucosa, in the susceptibility to the development of gastric lesions. METHODS： The study was performed with 99 samples of known gastric lesions and 127 samples without evidence of neoplastic disease. PCR was employed and the 6 polymorphic alleles were amplified： Allele 1 （510 bp）, Allele 2 （480 bp）, Allele 3/4 （450/460 bp）, Allele 5 （400 bp） and Allele 6 （310 bp）. RESULTS： Our results revealed that Allele 6 carriers seemed to have protection against the development of any gastric lesion （OR = 0.34; P 〈 0.001）, non-dysplastic lesions associated with gastric adenocarcinoma such as atrophy or intestinal metaplasia （OR = 0.28; P 〈 0.001） or invasive GC （OR = 0.39; P = 0.004）. CONCLUSION： Our study reveals that the Allele 6 carrier status has a protective role in the development of gastric lesions, probably due to its association with higher expression of PGC. Moreover, the frequency of Allele 6 carriers in the control group is far higher than that obtained in Asian populations, which might represent a genetic gap between Caucasian and Asian populations.展开更多
The most promising strategies in tissue engineering involve the integration of a triad of biomaterials, living cells, and biologically active molecules to engineer synthetic environments that closely mimic the healing...The most promising strategies in tissue engineering involve the integration of a triad of biomaterials, living cells, and biologically active molecules to engineer synthetic environments that closely mimic the healing milieu present in human tissues, and that stimulate tissue repair and regeneration. To be clinically effective, these environments must replicate, as closely as possible, the main characteristics of the native extracellular matrix(ECM) on a cellular and subcellular scale. Photo-fabrication techniques have already been used to generate 3D environments with precise architectures and heterogeneous composition, through a multi-layer procedure involving the selective photocrosslinking reaction of a light-sensitive prepolymer. Cells and therapeutic molecules can be included in the initial hydrogel precursor solution, and processed into 3D constructs. Recently, photofabrication has also been explored to dynamically modulate hydrogel features in real time, providing enhanced control of cell fate and delivery of bioactive compounds. This paper focuses on the use of 3D photo-fabrication techniques to produce advanced constructs for tissue regeneration and drug delivery applications. State-of-the-art photo-fabrication techniques are described, with emphasis on the operating principles and biofabrication strategies to create spatially controlled patterns of cells and bioactive factors. Considering its fast processing, spatiotemporal control, high resolution, and accuracy, photo-fabrication is assuming a critical role in the design of sophisticated 3D constructs. This technology is capable of providing appropriate environments for tissue regeneration, and regulating the spatiotemporal delivery of therapeutics.展开更多
Progress in the characterization of genes involved in the control of iron homeostasis in humans and in mice has improved the definition of iron overload and of the cells affected by it. The cell involved in iron overl...Progress in the characterization of genes involved in the control of iron homeostasis in humans and in mice has improved the definition of iron overload and of the cells affected by it. The cell involved in iron overload with the greatest effect on immunity is the macrophage. Intriguing evidence has emerged, however, in the last 12 years indicating that parenchymal iron overload is linked to genes classically associated with the immune system. This review offers an update of the genes and proteins relevant to iron metabolism expressed in cells of the innate immune system, and addresses the question of how this system is affected in clinical situations of iron overload. The relationship between iron and the major cells of adaptive immunity, the T lymphocytes, will also be reviewed. Most studies addressing this last question in humans were performed in the clinical model of Hereditary Hemochromatosis. Data will also be reviewed demonstrating howthe disruption of molecules essentially involved in adaptive immune responses result in the spontaneous development of iron overload and how they act as modifiers of iron overload.展开更多
Objective: To prove specific effects of acupuncture on chronic pain. It was speculated that the potential specific effectiveness of acupuncture could be better shown in more properly designed studies. Therefore, diagn...Objective: To prove specific effects of acupuncture on chronic pain. It was speculated that the potential specific effectiveness of acupuncture could be better shown in more properly designed studies. Therefore, diagnoses of both Western medicine and traditional Chinese medicine (TCM) were used as inclusion criteria to allocate acupoints more precisely to the complaints of the patients. Secondly, objectively measurable parameters of pain relief in addition to usual Visual Analogue Scale (VAS) were chosen to quantify the effects of acupuncture. Methods: The study was prospective, randomized, controlled and single-blinded. Eighteen patients with chronic back pain and TCM diagnosis of a Taiyang/Yangming syndrome received one single session of acupuncture chosen according to TCM diagnosis or acupuncture on points outside the meridian system (controls). We evaluated pain via VAS and increased mobility via inclinometry of the back. Results: Although the sample size was small, there was a statistically significant improvement in pain and mobility in the intervention group (n=13), but not in the control group (n=5). The calculated sample size adequate power was lower for inclinometry than for VAS, indicating that VAS is less probable to discriminate acupuncture effects. Conclusion: Objectively measurable physical parameters such as the angle of flexion before and after acupuncture (inclinometry) may be more suitable to measure pain relief than subjective assessment by VAS in acupuncture studies. TCM diagnosis may be a helpful inclusion criterion in studies on acupuncture, so as to potentially allocate interventions better to the complaints of patients.展开更多
Lipid droplets (LDs) are ubiquitous cellular orga nelles that perform functions mostly dedicated to energy homeostasis and lipid metabolism.As neutral lipid depots (triacylglycerol,sterol esters),they can be rapidly m...Lipid droplets (LDs) are ubiquitous cellular orga nelles that perform functions mostly dedicated to energy homeostasis and lipid metabolism.As neutral lipid depots (triacylglycerol,sterol esters),they can be rapidly mobilized through lipase-mediated hydrolysis (lipolysis) or via lipophagy,a specific form of autophagy devoted to consumption of LDs inside the lysosome.展开更多
Combination therapy via nanoparticulate systems has already been proposed as a synergistic approach for cancer treatment. Herein, undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles （UnTH...Combination therapy via nanoparticulate systems has already been proposed as a synergistic approach for cancer treatment. Herein, undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles （UnTHCPSi NPs） loaded with sorafenib and surface-biofunctionalized with anti-CD326 antibody （Ab） were developed for cancer chemo-immunotherapy in MCF-7 and MDA-MB-231 breast cancer cells. The cytocompatibility study showed no significant toxicity for the bare and antibody-conjugated UnTHCPSi （Un-Ab） NPs at concentrations lower than 200 μg·mL^-1. Compared to the bare UnTHCPSi, Un-Ab NPs loaded with sorafenib reduced the premature drug release in plasma, increasing the probability of proper drug targeting. In addition, high cellular interaction and subsequent internalization of the Un-Ab NPs into the cells expressing CD326 antigen demonstrated the possibility of improving antigen-mediated endocytosis via CD326 targeting. While an in vitro antitumor study revealed a higher inhibitory effect of the sorafenib-loaded Un-Ab NPs compared to the drug-loaded UnTHCPSi NPs in the CD326 positive MCF-7 cells, there was no difference in the anti-proliferation impact of both the abovementioned NPs in the CD326 negative MDA-MB-231 cells, suggesting CD326 as an appropriate receptor for Ab-mediated drug delivery. It was also shown that the anti-CD326 Ab can act as an immunotherapeutic agent by inducing antibody dependent cellular cytotoxicity and enhancing the interaction of effector immune and cancer cells for subsequent phagocytosis and cytokine secretion. Hence, the developed nanovectors can be applied for simultaneous tumor-selective drug targeting and immunotherapy.展开更多
Ovarian cancer(OC)is the sixth most common cancer and the seventh cause of death from cancer in women.The etiology and the ovarian carcinogenesis still need clarification although ovulation may be determinant due to i...Ovarian cancer(OC)is the sixth most common cancer and the seventh cause of death from cancer in women.The etiology and the ovarian carcinogenesis still need clarification although ovulation may be determinant due to its carcinogenic role in ovarian surface epithelium.The link between ovarian carcinogenesis and DNA repair is well established and it became clear that alterations in DNA damage response may affect the risk to develop OC.Polymorphisms are variations in the DNA sequence that exist in normal individuals of a population and are capable to change,among other mechanisms,the balance between DNA damage and cellular response.Consequently,genetic variability of the host has a great role in the development,progression and consequent prognosis of the oncologic patient as well as in treatment response.Standard treatment for OC patients is based on cytoreductive surgery,followed by chemotherapy with a platinum agent and a taxane.Although 80%of the patients respond to the first-line therapy,the development of resistance is common although the mechanisms underlying therapy failure remain mostly unknown.Because of their role in oncology,enzymes involved in the DNA repair pathways,like DNA Ligase IV(LIG4),became attractive study targets.It has been reported that variations in LIG4 activity can lead to a hyper-sensitivity to DNA damage,deregulation of repair and apoptosis mechanisms,affecting the susceptibility to cancer development and therapy response.To overcome resistance mechanisms,several investigations have been made and the strategy to target crucial molecular pathways,such as DNA repair,became one of the important areas in clinical oncology.This review aims to elucidate the link between DNA repair and OC,namely which concerns the role of LIG4 enzyme,and how genetic polymorphisms in LIG4 gene can modulate the activity of the enzyme and affect the ovarian carcinogenesis and treatment response.Moreover,we try to understand how LIG4 inhibition can be a potential contributor for the development of new cancer treatm展开更多
According to a modem understanding of acupuncture mechanisms, acupuncture may elicit vegetative reflexes, presumably influencing the systemwide vegetative dysregulation associated with the heart failure syndrome, a fe...According to a modem understanding of acupuncture mechanisms, acupuncture may elicit vegetative reflexes, presumably influencing the systemwide vegetative dysregulation associated with the heart failure syndrome, a feature of which is low performance in the 6 min walk test. The author performed a preliminary prospective, randomized, single-blinded clinical trial （n=21） in a cross-over design comparing acupuncture treatment, which was either compatible with individual Chinese diagnosis according to the Heidelberg Model of TCM （i-ACU） or a standardized treatment on acupoints with no specific relation to TCM diagnosis （u-ACU）. The repeated measures analysis revealed a significant effect for i-ACU vs. u-ACU （F =7.2, df=1.37, P=-0.011）. The study revealed first evidence that acupuncture may prolong 6 min walk distance as a key parameter of heart failure.展开更多
Defining the classical Chinese diagnosis such as by the Heidelberg model of TCM has shown that outcome of studies is largely dependent on classical diagnostic criteria. The quality of future studies in TCM will largel...Defining the classical Chinese diagnosis such as by the Heidelberg model of TCM has shown that outcome of studies is largely dependent on classical diagnostic criteria. The quality of future studies in TCM will largely depend on a variety of factors, such as （1） the classical Chinese diagnosis as an inclusion criterion, （2） objectively measurable parameters as the main criterion of outcome, （3） double blinding of controls. A common understanding of the diagnosis and functional criteria of TCM is therefore necessary, as well as a common understanding of the functional terminology and rationally accessible theory. This underlines the necessity of classical Chinese medical theory for modem scientific research, its proper definition and application in studies.展开更多
In this retrospective study we have investigated the anxiety as an impact of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Huntington disease (HD), Machado-Joseph disease (MJD)?and famili...In this retrospective study we have investigated the anxiety as an impact of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Huntington disease (HD), Machado-Joseph disease (MJD)?and familial amyloidotic polyneuropathy (FAP)?V30MTTR. The study included 686 subjects: 586 (85.4%) were the offspring at risk for FAP, 92 (13.4%) for HD and 8 (1.2%) to MJD. Of these, 352 received the carrier result and 305 the non-carrier result. As indicator of anxiety distress was taken the Self-Rating Anxiety Scale of Zung (SAS), applied in the pre-test and the three post-test moments: three weeks, 6 months and one year after notification of test results. Values decreased significantly along the four evaluation moments, regardless the studied disease or test result. For female population, SAS means cores revealed results of clinical anxiety at pre-test, only decreasing to non clinical scores a year after PST disclosure.展开更多
In this retrospective study, we have researched the psychological impact of pre-symptomatic testing (PST) for 2 autosomal dominant late-onset diseases: Huntington disease (HD and familial amyloidotic polyneuropathy (F...In this retrospective study, we have researched the psychological impact of pre-symptomatic testing (PST) for 2 autosomal dominant late-onset diseases: Huntington disease (HD and familial amyloidotic polyneuropathy (FAP) V30M TTR. The study included 53 subjects: 40 (75.5%) were the offspring at risk for FAP and 13 (24.5%) for HD. Of these, 38 (73.1%) received the carrier result and 12 (23.1%) the noncarrier result;3 of them did not want to know the result. The indicators taken for emotional distress were the subscales and global indexes of psychopathological Behavior Symptoms Inventory (BSI), applied in the pre-test and post-test, one-year after notification of results. Values decreased significantly one year after the implementation of the PST, regardless of the studied disease or test result;this seems to corroborate previous studies showing that testing does not increase pre-symptomatic levels of emotional disturbance in individuals. However, the subjects studied showed, for all subscales and global indexes of the BSI, significantly higher values than those of control groups.展开更多
The genetic bases and molecular mechanisms involved in the assembly and function of the flagellum components as well as in the regulation of the flagellar movement are not fully understood, especially in humans. There...The genetic bases and molecular mechanisms involved in the assembly and function of the flagellum components as well as in the regulation of the flagellar movement are not fully understood, especially in humans. There are several causes for sperm immotility, of which some can be avoided and corrected, whereas other are related to genetic defects and deserve full investigation to give a diagnosis to patients. This review was performed after an extensive literature search on the online databases PubMed, ScienceDirect, and Web of Science. Here, we review the involvement of regulatory pathways responsible for sperm motility, indicating possible causes for sperm immotility. These included the calcium pathway, the cAMP-dependent protein kinase pathway, the importance of kinases and phosphatases, the function of reactive oxygen species, and how the regulation of cell volume and osmolarity are also fundamental components. We then discuss main gene defects associated with specific morphological abnormalities. Finally, we slightly discuss some preventive and treatments approaches to avoid development of conditions that are associated with unspecified sperm immotility. We believe that in the near future, with the development of more powerful techniques, the genetic causes of sperm immotility and the regulatory mechanisms of sperm motility will be better understand, thus enabling to perform a full diagnosis and uncover new therapies.展开更多
Lung cancer is currently the leading cause of cancer death in Western nations.Non-small cell lung cancer(NSCLC)represents 80%of all lung cancers,and adenocarcinoma is the predominant histological type.Despite the inte...Lung cancer is currently the leading cause of cancer death in Western nations.Non-small cell lung cancer(NSCLC)represents 80%of all lung cancers,and adenocarcinoma is the predominant histological type.Despite the intensive research carried out on this field and therapeutic advances,the overall prognosis of these patients remains unsatisfactory,with a 5-year overall survival rate of less than 15%.Nowadays,pharmacogenetics and pharmacogenomics represent the key to successful treatment.Recent studies suggest the existence of two distinct molecular pathways in the carcinogenesis of lung adenocarcinoma:one associated with smoking and activation of the K-Ras oncogene and the other not associated with smoking and activation of the epidermal growth factor receptor(EGFR).The K-ras mutation is mainly responsible for primary resistance to new molecules which inhibit tyrosine kinase EGFR(erlotinib and gefitinib)and most of the EGFR mutations are responsible for increased tumor sensitivity to these drugs.This article aims to conduct a systematic review of the literature regarding the molecular pathways involving the EGFR,K-Ras and EGFR targeted therapies in NSCLC tumor behavior.展开更多
Osteoporosis is a systemic disease that results in loss of bone density and increased fracture risk,particularly in the vertebrae and the hip.This condition and associated morbidity and mortality increase with populat...Osteoporosis is a systemic disease that results in loss of bone density and increased fracture risk,particularly in the vertebrae and the hip.This condition and associated morbidity and mortality increase with population ageing.Long noncoding(lnc)RNAs are transcripts longer than 200 nucleotides that are not translated into proteins,but play important regulatory roles in transcriptional and post-transcriptional regulation.Their contribution to disease onset and development is increasingly recognized.Herein,we present an integrative revision on the studies that implicate lncRNAs in osteoporosis and that support their potential use as therapeutic tools.Firstly,current evidence on lncRNAs involvement in cellular and molecular mechanisms linked to osteoporosis and its major complication,fragility fractures,is reviewed.We analyze evidence of their roles in osteogenesis,osteoclastogenesis,and bone fracture healing events from human and animal model studies.Secondly,the potential of lncRNAs alterations at genetic and transcriptomic level are discussed as osteoporosis risk factors and as new circulating biomarkers for diagnosis.Finally,we conclude debating the possibilities,persisting difficulties,and future prospects of using lncRNAs in the treatment of osteoporosis.展开更多
The aim of the present work was to present the outcomes of the patients with Y-chromosome microdeletions treated by intracytoplasmic sperm injection （ICSI）, either using fresh （TESE） or frozen-thawed （TESE-C） te...The aim of the present work was to present the outcomes of the patients with Y-chromosome microdeletions treated by intracytoplasmic sperm injection （ICSI）, either using fresh （TESE） or frozen-thawed （TESE-C） testicular sperm and ejaculated sperm （EJAC）. The originality of this work resides in the comparisons between the different types of Y-microdeletions （AZFa, AZFb, and AZFc） and treatments, with detailed demographic, stimulation, embryological, clinical, and newborn （NB） outcomes. Of 125 patients with Y-microdeletions, 33 patients presented severe oligozoospermia （18 performed ICSI with ejaculated sperm） and 92 secretory azoospermia （65 went for TESE with 40 having successful sperm retrieval and performed ICSI）. There were 51 TESE treatment cycles and 43 TESE-C treatment cycles, with a birth of 19 NB （2 in AZFa/TESE-C, 12 in AZFc/TESE, and 5 in AZFc/TESE-C）. Of the 29 EJAC cycles, there was a birth of 8 NB （in AZFc）. In TESE and EJAC cycles, there were no significant differences in embryological and clinical parameters. In TESE-C cycles, there was a significant lower oocyte maturity rate, embryo cleavage rate and mean number of embryos transferred in AZFb, and a higher mean number of oocytes and lower fertilization rate in AZFc. In conclusion, although patients with AZFc microdeletions presented a high testicular sperm recovery rate and acceptable clinical outcomes, cases with AZFa and AZFb microdeletions presented a poor prognosis. Due to the reported heredity of microdeletions, patients should be informed about the infertile consequences on NB and the possibility of using preimplantation genetic diagnosis for female sex selection.展开更多
T-cell development ensures the formation of diverse repertoires of T-cell receptors(TCRs)that recognize a variety of antigens.Glycosylation is a major posttranslational modification present in virtually all cells,incl...T-cell development ensures the formation of diverse repertoires of T-cell receptors(TCRs)that recognize a variety of antigens.Glycosylation is a major posttranslational modification present in virtually all cells,including T-lymphocytes,that regulates activity/functions.Although these structures are known to be involved in TCR-selection in DP thymocytes,it is unclear how glycans regulate other thymic development processes and how they influence susceptibility to disease.Here,we discovered stage-specific glycome compositions during T-cell development in human and murine thymocytes,as well as dynamic alterations.After restricting the N-glycosylation profile of thymocytes to high-mannose structures,using specific glycoengineered mice(Rag1CreMgat1fl/fl),we showed remarkable defects in key developmental checkpoints,includingß-selection,regulatory T-cell generation andγδT-cell development,associated with increased susceptibility to colon and kidney inflammation and infection.We further demonstrated that a single N-glycan antenna(modeled in Rag1CreMgat2fl/fl mice)is the sine-qua-non condition to ensure normal development.In conclusion,we revealed that mannosylated thymocytes lead to a dysregulation in T-cell development that is associated with inflammation susceptibility.展开更多
Tissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of axons.Sensory innervation is part of the ne...Tissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of axons.Sensory innervation is part of the neuronal network of the bone tissue with a defined spatiotemporal occurrence during bone development.Yet,the current understanding of the mechanisms regulating the map of sensory innervation in the bone tissue is still limited.Here,we demonstrated that differentiation of human mesenchymal stem cells to osteoblasts leads to a marked impairment of their ability to promote axonal growth,evidenced under sensory neurons and osteoblastic-lineage cells crosstalk.The mechanisms by which osteoblast lineage cells provide this nonpermissive environment for axons include paracrine-induced repulsion and loss of neurotrophic factors expression.We identified a drastic reduction of NGF and BDNF production and stimulation of Sema3A,Wnt4;and Shh expression culminating at late stage of OB differentiation.We noted a correlation between Shh expression profile,OB differentiation stages,and OB-mediated axonal repulsion.Blockade of Shh activity and signaling reversed the repulsive action of osteoblasts on sensory axons.Finally,to strengthen our model,we localized the expression of Shh by osteoblasts in bone tissue.Overall,our findings provide evidence that the signaling profile associated with osteoblast phenotype differentiating program can regulate the patterning of sensory innervation,and highlight osteoblast-derived Shh as an essential player in this cue-induced regulation.展开更多
BACKGROUND The impact caused by the coronavirus disease 2019(COVID-19)on the Portuguese population has been addressed in areas such as clinical manifestations,frequent comorbidities,and alterations in consumption habi...BACKGROUND The impact caused by the coronavirus disease 2019(COVID-19)on the Portuguese population has been addressed in areas such as clinical manifestations,frequent comorbidities,and alterations in consumption habits.However,comorbidities like liver conditions and changes concerning the Portuguese population's access to healthcare-related services have received less attention.AIM To(1)Review the impact of COVID-19 on the healthcare system;(2)examine the relationship between liver diseases and COVID-19 in infected individuals;and(3)investigate the situation in the Portuguese population concerning these topics.METHODS For our purposes,we conducted a literature review using specific keywords.RESULTS COVID-19 is frequently associated with liver damage.However,liver injury in COVID-19 individuals is a multifactor-mediated effect.Therefore,it remains unclear whether changes in liver laboratory tests are associated with a worse prognosis in Portuguese individuals with COVID-19.CONCLUSION COVID-19 has impacted healthcare systems in Portugal and other countries;the combination of COVID-19 with liver injury is common.Previous liver damage may represent a risk factor that worsens the prognosis in individuals with COVID-19.展开更多
基金Supported by the Portuguese League Against Cancer (Liga Portuguesa Contra o Cancro-Núcleo Regional do Norte) and AstraZeneca Foundation
文摘AIM： To investigate the relationship between the -765G 〉 C COX-2 polymorphism and the development of different gastric lesions： atrophy or intestinal metaplasia and gastric adenocarcinoma. METHODS： A cross-sectional study was performed involving 320 Portuguese individuals （210 without evidence of neoplastic disease, 73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal metaplasia） using a PCR-RFLP method.RESULTS： -765C allele was overrepresented in the patients with gastric adenocarcinoma （51%） when compared either with the control group （38%） or patients with atrophy or intestinal metaplasia （27%）. Callele was found to be very common in our population （0.22）, and a multivariate logistic regression analysis revealed nearly 3-fold increased risk for the progression to gastric adenocarcinoma in patients with atrophy or intestinal metaplasia carrying the -765C allele （OR = 2.67, 95% CI = 1.03-6.93; P = 0.04）.CONCLUSION： -765C carrier status should be considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.
文摘Interleukin-6(IL-6)is a pleiotropic cytokine involved in prostate regulation and in prostate cancer(PC)development/progression.IL-6 acts as a paracrine and autocrine growth stimulator in benign and tumor prostate cells.The levels of IL-6 and respective receptors are increased during prostate carcinogenesis and tumor progression.Several studies reported that increased serum and plasma IL-6 and soluble interleukin-6 receptor levels are associated with aggressiveness of the disease and are associated with a poor prognosis in PC patients.In PC treatment,patients diagnosed with advanced stages are frequently submitted to hormonal castration,although most patients will eventually fail this therapy and die from recurrent castration-resistant prostate cancer(CRPC).Therefore,it is important to understand the mechanisms involved in CRPC.Several pathways have been proposed to be involved in CRPC development,and their understanding will improve the way to more effective therapies.In fact,the prostate is known to be dependent,not exclusively,on androgens,but also on growth factors and cytokines.The signaling pathway mediated by IL-6 may be an alternative pathway in the CRPC phenotype acquisition and cancer progression,under androgen deprivation conditions.The principal goal of this review is to evaluate the role of IL-6 pathway signaling in human PC development and progression and discuss the interaction of this pathway with the androgen recepto pathway.Furthermore,we intend to evaluate the inclusion of IL-6 and its receptor levels as a putative new class of tumor biomarkers.The IL-6/IL-6R signaling pathway may be included as a putative molecular marker for aggressiveness in PC and it may be able to maintain tumor growth through the AR pathway under androgen-deprivation conditions.The importance of the IL-6/IL-6R pathway in regulation of PC cells makes it a good candidate for targeted therapy.
基金Supported by the Portuguese League Against Cancer (Liga Por-tuguesa Contra o Cancro-Nucleo Regional do Norte) and Astra Zeneca Foundation
文摘AIM： To study the role of an insertion/deletion polymorphism in the pepsinogen C （PGC） gene, an effective marker for terminal differentiation of the stomach mucosa, in the susceptibility to the development of gastric lesions. METHODS： The study was performed with 99 samples of known gastric lesions and 127 samples without evidence of neoplastic disease. PCR was employed and the 6 polymorphic alleles were amplified： Allele 1 （510 bp）, Allele 2 （480 bp）, Allele 3/4 （450/460 bp）, Allele 5 （400 bp） and Allele 6 （310 bp）. RESULTS： Our results revealed that Allele 6 carriers seemed to have protection against the development of any gastric lesion （OR = 0.34; P 〈 0.001）, non-dysplastic lesions associated with gastric adenocarcinoma such as atrophy or intestinal metaplasia （OR = 0.28; P 〈 0.001） or invasive GC （OR = 0.39; P = 0.004）. CONCLUSION： Our study reveals that the Allele 6 carrier status has a protective role in the development of gastric lesions, probably due to its association with higher expression of PGC. Moreover, the frequency of Allele 6 carriers in the control group is far higher than that obtained in Asian populations, which might represent a genetic gap between Caucasian and Asian populations.
基金support of the Portuguese Foundation for Science and Technology (FCT) through the strategic project UID/Multi/04044/2013the FCT for the doctoral grant SFRH/BD/91151/2012
文摘The most promising strategies in tissue engineering involve the integration of a triad of biomaterials, living cells, and biologically active molecules to engineer synthetic environments that closely mimic the healing milieu present in human tissues, and that stimulate tissue repair and regeneration. To be clinically effective, these environments must replicate, as closely as possible, the main characteristics of the native extracellular matrix(ECM) on a cellular and subcellular scale. Photo-fabrication techniques have already been used to generate 3D environments with precise architectures and heterogeneous composition, through a multi-layer procedure involving the selective photocrosslinking reaction of a light-sensitive prepolymer. Cells and therapeutic molecules can be included in the initial hydrogel precursor solution, and processed into 3D constructs. Recently, photofabrication has also been explored to dynamically modulate hydrogel features in real time, providing enhanced control of cell fate and delivery of bioactive compounds. This paper focuses on the use of 3D photo-fabrication techniques to produce advanced constructs for tissue regeneration and drug delivery applications. State-of-the-art photo-fabrication techniques are described, with emphasis on the operating principles and biofabrication strategies to create spatially controlled patterns of cells and bioactive factors. Considering its fast processing, spatiotemporal control, high resolution, and accuracy, photo-fabrication is assuming a critical role in the design of sophisticated 3D constructs. This technology is capable of providing appropriate environments for tissue regeneration, and regulating the spatiotemporal delivery of therapeutics.
基金Portuguese Foundation for Science and Technology and Calouste Gulbenkian Foundation
文摘Progress in the characterization of genes involved in the control of iron homeostasis in humans and in mice has improved the definition of iron overload and of the cells affected by it. The cell involved in iron overload with the greatest effect on immunity is the macrophage. Intriguing evidence has emerged, however, in the last 12 years indicating that parenchymal iron overload is linked to genes classically associated with the immune system. This review offers an update of the genes and proteins relevant to iron metabolism expressed in cells of the innate immune system, and addresses the question of how this system is affected in clinical situations of iron overload. The relationship between iron and the major cells of adaptive immunity, the T lymphocytes, will also be reviewed. Most studies addressing this last question in humans were performed in the clinical model of Hereditary Hemochromatosis. Data will also be reviewed demonstrating howthe disruption of molecules essentially involved in adaptive immune responses result in the spontaneous development of iron overload and how they act as modifiers of iron overload.
文摘Objective: To prove specific effects of acupuncture on chronic pain. It was speculated that the potential specific effectiveness of acupuncture could be better shown in more properly designed studies. Therefore, diagnoses of both Western medicine and traditional Chinese medicine (TCM) were used as inclusion criteria to allocate acupoints more precisely to the complaints of the patients. Secondly, objectively measurable parameters of pain relief in addition to usual Visual Analogue Scale (VAS) were chosen to quantify the effects of acupuncture. Methods: The study was prospective, randomized, controlled and single-blinded. Eighteen patients with chronic back pain and TCM diagnosis of a Taiyang/Yangming syndrome received one single session of acupuncture chosen according to TCM diagnosis or acupuncture on points outside the meridian system (controls). We evaluated pain via VAS and increased mobility via inclinometry of the back. Results: Although the sample size was small, there was a statistically significant improvement in pain and mobility in the intervention group (n=13), but not in the control group (n=5). The calculated sample size adequate power was lower for inclinometry than for VAS, indicating that VAS is less probable to discriminate acupuncture effects. Conclusion: Objectively measurable physical parameters such as the angle of flexion before and after acupuncture (inclinometry) may be more suitable to measure pain relief than subjective assessment by VAS in acupuncture studies. TCM diagnosis may be a helpful inclusion criterion in studies on acupuncture, so as to potentially allocate interventions better to the complaints of patients.
文摘Lipid droplets (LDs) are ubiquitous cellular orga nelles that perform functions mostly dedicated to energy homeostasis and lipid metabolism.As neutral lipid depots (triacylglycerol,sterol esters),they can be rapidly mobilized through lipase-mediated hydrolysis (lipolysis) or via lipophagy,a specific form of autophagy devoted to consumption of LDs inside the lysosome.
文摘Combination therapy via nanoparticulate systems has already been proposed as a synergistic approach for cancer treatment. Herein, undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles （UnTHCPSi NPs） loaded with sorafenib and surface-biofunctionalized with anti-CD326 antibody （Ab） were developed for cancer chemo-immunotherapy in MCF-7 and MDA-MB-231 breast cancer cells. The cytocompatibility study showed no significant toxicity for the bare and antibody-conjugated UnTHCPSi （Un-Ab） NPs at concentrations lower than 200 μg·mL^-1. Compared to the bare UnTHCPSi, Un-Ab NPs loaded with sorafenib reduced the premature drug release in plasma, increasing the probability of proper drug targeting. In addition, high cellular interaction and subsequent internalization of the Un-Ab NPs into the cells expressing CD326 antigen demonstrated the possibility of improving antigen-mediated endocytosis via CD326 targeting. While an in vitro antitumor study revealed a higher inhibitory effect of the sorafenib-loaded Un-Ab NPs compared to the drug-loaded UnTHCPSi NPs in the CD326 positive MCF-7 cells, there was no difference in the anti-proliferation impact of both the abovementioned NPs in the CD326 negative MDA-MB-231 cells, suggesting CD326 as an appropriate receptor for Ab-mediated drug delivery. It was also shown that the anti-CD326 Ab can act as an immunotherapeutic agent by inducing antibody dependent cellular cytotoxicity and enhancing the interaction of effector immune and cancer cells for subsequent phagocytosis and cytokine secretion. Hence, the developed nanovectors can be applied for simultaneous tumor-selective drug targeting and immunotherapy.
基金Supported by Research Department of Portuguese League against Cancer(NRNorte)and Minister of Health of Portugal(CFICS-45/2007)
文摘Ovarian cancer(OC)is the sixth most common cancer and the seventh cause of death from cancer in women.The etiology and the ovarian carcinogenesis still need clarification although ovulation may be determinant due to its carcinogenic role in ovarian surface epithelium.The link between ovarian carcinogenesis and DNA repair is well established and it became clear that alterations in DNA damage response may affect the risk to develop OC.Polymorphisms are variations in the DNA sequence that exist in normal individuals of a population and are capable to change,among other mechanisms,the balance between DNA damage and cellular response.Consequently,genetic variability of the host has a great role in the development,progression and consequent prognosis of the oncologic patient as well as in treatment response.Standard treatment for OC patients is based on cytoreductive surgery,followed by chemotherapy with a platinum agent and a taxane.Although 80%of the patients respond to the first-line therapy,the development of resistance is common although the mechanisms underlying therapy failure remain mostly unknown.Because of their role in oncology,enzymes involved in the DNA repair pathways,like DNA Ligase IV(LIG4),became attractive study targets.It has been reported that variations in LIG4 activity can lead to a hyper-sensitivity to DNA damage,deregulation of repair and apoptosis mechanisms,affecting the susceptibility to cancer development and therapy response.To overcome resistance mechanisms,several investigations have been made and the strategy to target crucial molecular pathways,such as DNA repair,became one of the important areas in clinical oncology.This review aims to elucidate the link between DNA repair and OC,namely which concerns the role of LIG4 enzyme,and how genetic polymorphisms in LIG4 gene can modulate the activity of the enzyme and affect the ovarian carcinogenesis and treatment response.Moreover,we try to understand how LIG4 inhibition can be a potential contributor for the development of new cancer treatm
文摘According to a modem understanding of acupuncture mechanisms, acupuncture may elicit vegetative reflexes, presumably influencing the systemwide vegetative dysregulation associated with the heart failure syndrome, a feature of which is low performance in the 6 min walk test. The author performed a preliminary prospective, randomized, single-blinded clinical trial （n=21） in a cross-over design comparing acupuncture treatment, which was either compatible with individual Chinese diagnosis according to the Heidelberg Model of TCM （i-ACU） or a standardized treatment on acupoints with no specific relation to TCM diagnosis （u-ACU）. The repeated measures analysis revealed a significant effect for i-ACU vs. u-ACU （F =7.2, df=1.37, P=-0.011）. The study revealed first evidence that acupuncture may prolong 6 min walk distance as a key parameter of heart failure.
文摘Defining the classical Chinese diagnosis such as by the Heidelberg model of TCM has shown that outcome of studies is largely dependent on classical diagnostic criteria. The quality of future studies in TCM will largely depend on a variety of factors, such as （1） the classical Chinese diagnosis as an inclusion criterion, （2） objectively measurable parameters as the main criterion of outcome, （3） double blinding of controls. A common understanding of the diagnosis and functional criteria of TCM is therefore necessary, as well as a common understanding of the functional terminology and rationally accessible theory. This underlines the necessity of classical Chinese medical theory for modem scientific research, its proper definition and application in studies.
文摘In this retrospective study we have investigated the anxiety as an impact of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Huntington disease (HD), Machado-Joseph disease (MJD)?and familial amyloidotic polyneuropathy (FAP)?V30MTTR. The study included 686 subjects: 586 (85.4%) were the offspring at risk for FAP, 92 (13.4%) for HD and 8 (1.2%) to MJD. Of these, 352 received the carrier result and 305 the non-carrier result. As indicator of anxiety distress was taken the Self-Rating Anxiety Scale of Zung (SAS), applied in the pre-test and the three post-test moments: three weeks, 6 months and one year after notification of test results. Values decreased significantly along the four evaluation moments, regardless the studied disease or test result. For female population, SAS means cores revealed results of clinical anxiety at pre-test, only decreasing to non clinical scores a year after PST disclosure.
文摘In this retrospective study, we have researched the psychological impact of pre-symptomatic testing (PST) for 2 autosomal dominant late-onset diseases: Huntington disease (HD and familial amyloidotic polyneuropathy (FAP) V30M TTR. The study included 53 subjects: 40 (75.5%) were the offspring at risk for FAP and 13 (24.5%) for HD. Of these, 38 (73.1%) received the carrier result and 12 (23.1%) the noncarrier result;3 of them did not want to know the result. The indicators taken for emotional distress were the subscales and global indexes of psychopathological Behavior Symptoms Inventory (BSI), applied in the pre-test and post-test, one-year after notification of results. Values decreased significantly one year after the implementation of the PST, regardless of the studied disease or test result;this seems to corroborate previous studies showing that testing does not increase pre-symptomatic levels of emotional disturbance in individuals. However, the subjects studied showed, for all subscales and global indexes of the BSI, significantly higher values than those of control groups.
文摘The genetic bases and molecular mechanisms involved in the assembly and function of the flagellum components as well as in the regulation of the flagellar movement are not fully understood, especially in humans. There are several causes for sperm immotility, of which some can be avoided and corrected, whereas other are related to genetic defects and deserve full investigation to give a diagnosis to patients. This review was performed after an extensive literature search on the online databases PubMed, ScienceDirect, and Web of Science. Here, we review the involvement of regulatory pathways responsible for sperm motility, indicating possible causes for sperm immotility. These included the calcium pathway, the cAMP-dependent protein kinase pathway, the importance of kinases and phosphatases, the function of reactive oxygen species, and how the regulation of cell volume and osmolarity are also fundamental components. We then discuss main gene defects associated with specific morphological abnormalities. Finally, we slightly discuss some preventive and treatments approaches to avoid development of conditions that are associated with unspecified sperm immotility. We believe that in the near future, with the development of more powerful techniques, the genetic causes of sperm immotility and the regulatory mechanisms of sperm motility will be better understand, thus enabling to perform a full diagnosis and uncover new therapies.
文摘Lung cancer is currently the leading cause of cancer death in Western nations.Non-small cell lung cancer(NSCLC)represents 80%of all lung cancers,and adenocarcinoma is the predominant histological type.Despite the intensive research carried out on this field and therapeutic advances,the overall prognosis of these patients remains unsatisfactory,with a 5-year overall survival rate of less than 15%.Nowadays,pharmacogenetics and pharmacogenomics represent the key to successful treatment.Recent studies suggest the existence of two distinct molecular pathways in the carcinogenesis of lung adenocarcinoma:one associated with smoking and activation of the K-Ras oncogene and the other not associated with smoking and activation of the epidermal growth factor receptor(EGFR).The K-ras mutation is mainly responsible for primary resistance to new molecules which inhibit tyrosine kinase EGFR(erlotinib and gefitinib)and most of the EGFR mutations are responsible for increased tumor sensitivity to these drugs.This article aims to conduct a systematic review of the literature regarding the molecular pathways involving the EGFR,K-Ras and EGFR targeted therapies in NSCLC tumor behavior.
基金supported by Portuguese funds through FCT—Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia,Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-031402—R2Bonethe PORTUGAL 2020 Partnership Agreement,through ERDF+1 种基金FCT DL 57/2016/CP1360/CT0008 (M.I.A.)SFRH/BD/112832/2015 (J.H.T)
文摘Osteoporosis is a systemic disease that results in loss of bone density and increased fracture risk,particularly in the vertebrae and the hip.This condition and associated morbidity and mortality increase with population ageing.Long noncoding(lnc)RNAs are transcripts longer than 200 nucleotides that are not translated into proteins,but play important regulatory roles in transcriptional and post-transcriptional regulation.Their contribution to disease onset and development is increasingly recognized.Herein,we present an integrative revision on the studies that implicate lncRNAs in osteoporosis and that support their potential use as therapeutic tools.Firstly,current evidence on lncRNAs involvement in cellular and molecular mechanisms linked to osteoporosis and its major complication,fragility fractures,is reviewed.We analyze evidence of their roles in osteogenesis,osteoclastogenesis,and bone fracture healing events from human and animal model studies.Secondly,the potential of lncRNAs alterations at genetic and transcriptomic level are discussed as osteoporosis risk factors and as new circulating biomarkers for diagnosis.Finally,we conclude debating the possibilities,persisting difficulties,and future prospects of using lncRNAs in the treatment of osteoporosis.
文摘The aim of the present work was to present the outcomes of the patients with Y-chromosome microdeletions treated by intracytoplasmic sperm injection （ICSI）, either using fresh （TESE） or frozen-thawed （TESE-C） testicular sperm and ejaculated sperm （EJAC）. The originality of this work resides in the comparisons between the different types of Y-microdeletions （AZFa, AZFb, and AZFc） and treatments, with detailed demographic, stimulation, embryological, clinical, and newborn （NB） outcomes. Of 125 patients with Y-microdeletions, 33 patients presented severe oligozoospermia （18 performed ICSI with ejaculated sperm） and 92 secretory azoospermia （65 went for TESE with 40 having successful sperm retrieval and performed ICSI）. There were 51 TESE treatment cycles and 43 TESE-C treatment cycles, with a birth of 19 NB （2 in AZFa/TESE-C, 12 in AZFc/TESE, and 5 in AZFc/TESE-C）. Of the 29 EJAC cycles, there was a birth of 8 NB （in AZFc）. In TESE and EJAC cycles, there were no significant differences in embryological and clinical parameters. In TESE-C cycles, there was a significant lower oocyte maturity rate, embryo cleavage rate and mean number of embryos transferred in AZFb, and a higher mean number of oocytes and lower fertilization rate in AZFc. In conclusion, although patients with AZFc microdeletions presented a high testicular sperm recovery rate and acceptable clinical outcomes, cases with AZFa and AZFb microdeletions presented a poor prognosis. Due to the reported heredity of microdeletions, patients should be informed about the infertile consequences on NB and the possibility of using preimplantation genetic diagnosis for female sex selection.
基金Funded by the“2022 Lupus Research Alliance(LRA)Lupus Innovation Award”.Institutional funding from the Portuguese Foundation for Science and Technology(FCT):projects NORTE-01-0145-FEDER-000029,POCI-01/0145-FEDER-016601,POCI-01-0145-FEDER-028772,and PTDC/MEC-REU/28772/2017(SSP)This study was co-funded by the European Union(ERC Synergy,GlycanSwitch,101071386)+1 种基金Views and opinions expressed are,however,those of the author(s)only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency.The study was also co-funded by the European Union,GlycanTrigger project,Grant Agreement No:101093997Views and opinions expressed are,however,those of the author(s)only and do not necessarily reflect those of the European Union or European Health and Digital Executive Agency.Neither the European Union nor the granting authority can be held responsible for them.A grant was received from the Portuguese group of study in autoimmune diseases(NEDAI)to SSP.MMV(PD/BD/135452/2017,COVID/BD/152488/2022)received funding from the FCT.
文摘T-cell development ensures the formation of diverse repertoires of T-cell receptors(TCRs)that recognize a variety of antigens.Glycosylation is a major posttranslational modification present in virtually all cells,including T-lymphocytes,that regulates activity/functions.Although these structures are known to be involved in TCR-selection in DP thymocytes,it is unclear how glycans regulate other thymic development processes and how they influence susceptibility to disease.Here,we discovered stage-specific glycome compositions during T-cell development in human and murine thymocytes,as well as dynamic alterations.After restricting the N-glycosylation profile of thymocytes to high-mannose structures,using specific glycoengineered mice(Rag1CreMgat1fl/fl),we showed remarkable defects in key developmental checkpoints,includingß-selection,regulatory T-cell generation andγδT-cell development,associated with increased susceptibility to colon and kidney inflammation and infection.We further demonstrated that a single N-glycan antenna(modeled in Rag1CreMgat2fl/fl mice)is the sine-qua-non condition to ensure normal development.In conclusion,we revealed that mannosylated thymocytes lead to a dysregulation in T-cell development that is associated with inflammation susceptibility.
基金Claudia Machado(Instituto de Investigacao e Inovacao em Saude)for her help in preparing the bone slides for the immunohistochemistryThis work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation(POCI),Portugal 2020,and by Portuguese funds through FCT/MCTES in the framework of the project SproutcORE—Inervagao patologica em metastases osseas:OSTEOCLASTOS,o que estao a fazer?(PTDC/MED-PAT/30158/2017,POCI-01-0145-FEDER-030158)+1 种基金D.M.S.is a recipient of a Post-Doc fellowship(SFRH/BPD/115341/2016)L.L.and F.C.are recipients of Ph.D.fellowships(SFRH/BD/109686/2015 and SFRH/BD/128771/2017,respectively).
文摘Tissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of axons.Sensory innervation is part of the neuronal network of the bone tissue with a defined spatiotemporal occurrence during bone development.Yet,the current understanding of the mechanisms regulating the map of sensory innervation in the bone tissue is still limited.Here,we demonstrated that differentiation of human mesenchymal stem cells to osteoblasts leads to a marked impairment of their ability to promote axonal growth,evidenced under sensory neurons and osteoblastic-lineage cells crosstalk.The mechanisms by which osteoblast lineage cells provide this nonpermissive environment for axons include paracrine-induced repulsion and loss of neurotrophic factors expression.We identified a drastic reduction of NGF and BDNF production and stimulation of Sema3A,Wnt4;and Shh expression culminating at late stage of OB differentiation.We noted a correlation between Shh expression profile,OB differentiation stages,and OB-mediated axonal repulsion.Blockade of Shh activity and signaling reversed the repulsive action of osteoblasts on sensory axons.Finally,to strengthen our model,we localized the expression of Shh by osteoblasts in bone tissue.Overall,our findings provide evidence that the signaling profile associated with osteoblast phenotype differentiating program can regulate the patterning of sensory innervation,and highlight osteoblast-derived Shh as an essential player in this cue-induced regulation.
文摘BACKGROUND The impact caused by the coronavirus disease 2019(COVID-19)on the Portuguese population has been addressed in areas such as clinical manifestations,frequent comorbidities,and alterations in consumption habits.However,comorbidities like liver conditions and changes concerning the Portuguese population's access to healthcare-related services have received less attention.AIM To(1)Review the impact of COVID-19 on the healthcare system;(2)examine the relationship between liver diseases and COVID-19 in infected individuals;and(3)investigate the situation in the Portuguese population concerning these topics.METHODS For our purposes,we conducted a literature review using specific keywords.RESULTS COVID-19 is frequently associated with liver damage.However,liver injury in COVID-19 individuals is a multifactor-mediated effect.Therefore,it remains unclear whether changes in liver laboratory tests are associated with a worse prognosis in Portuguese individuals with COVID-19.CONCLUSION COVID-19 has impacted healthcare systems in Portugal and other countries;the combination of COVID-19 with liver injury is common.Previous liver damage may represent a risk factor that worsens the prognosis in individuals with COVID-19.
