Colorectal cancer(CRC)is the third most commonly diagnosed cancer globally and the second cancer in terms of mortality.The prevalence of sarcopenia in patients with CRC ranges between 12%-60%.Sarcopenia comes from the...Colorectal cancer(CRC)is the third most commonly diagnosed cancer globally and the second cancer in terms of mortality.The prevalence of sarcopenia in patients with CRC ranges between 12%-60%.Sarcopenia comes from the Greek“sarx”for flesh,and“penia”for loss.Sarcopenia is considered a phenomenon of the aging process and precedes the onset of frailty(primary sarcopenia),but sarcopenia may also result from pathogenic mechanisms and that disorder is termed secondary sarcopenia.Sarcopenia diagnosis is confirmed by the presence of low muscle quantity or quality.Three parameters need to be measured:muscle strength,muscle quantity and physical performance.The standard method to evaluate muscle mass is by analyzing the tomographic total cross-sectional area of all muscle groups at the level of lumbar 3rd vertebra.Sarcopenia may negatively impact on the postoperative outcomes of patients with colorectal cancer undergoing surgical resection.It has been described an association between sarcopenia and numerous poor short-term CRC outcomes like increased perioperative mortality,postoperative sepsis,prolonged length of stay,increased cost of care and physical disability.Sarcopenia may also negatively impact on overall survival,disease-free survival,recurrence-free survival,and cancerspecific survival in patients with non-metastatic and metastatic colorectal cancer.Furthermore,patients with sarcopenia seem prone to toxic effects during chemotherapy,requiring dose deescalations or treatment delays,which seems to reduce treatment efficacy.A multimodal approach including nutritional support(dietary intake,high energy,high protein,and omega-3 fatty acids),exercise programs and anabolic-orexigenic agents(ghrelin,anamorelin),could contribute to muscle mass preservation.Addition of sarcopenia screening to the established clinical-pathological scores for patients undergoing oncological treatment(chemotherapy,radiotherapy or surgery)seems to be the next step for the best of care of CRC patients.展开更多
We previously demonstrated that lipopolysaccharide(LPS)injection-induced immune stress could impair muscle growth in weaned piglets,but the precise mechanisms behind this remain elusive.Here,we found that chronic immu...We previously demonstrated that lipopolysaccharide(LPS)injection-induced immune stress could impair muscle growth in weaned piglets,but the precise mechanisms behind this remain elusive.Here,we found that chronic immune stress induced by LPS resulted in a significant reduction of 36.86%in the total muscle mass of piglets at 5 d post-treatment compared with the control group.At 1 d,prior to muscle mass loss,multiple alterations were noted in response to LPS treatment.These included a reduction in the abundance of Bacteroidetes,an increase in serum concentrations of pro-inflammatory cytokines,compromised mitochondrial morphology,and an upregulation in the expression of dynamin-related protein 1(Drp1),a critical protein involved in mitochondrial fission.We highlight a strong negative correlation between Bacteroidetes abundance and the levels of serum pro-inflammatory cytokines,corroborated by in vivo intervention strategies in the musculature of both pig and mouse models.Mechanistically,the effects of Bacteroidetes on inflammation and muscle mass loss may involve the signaling pathway of the tauro-β-muricholic acid-fibroblast growth factor 15.Furthermore,the induction of overexpression of inflammatory cytokines,achieved without LPS treatment through oral administration of recombinant human IL-6(rh IL-6),led to increased levels of circulating cytokines,subsequently causing a decrease in muscle mass.Notably,pre-treatment with Mdivi-1,an inhibitor of Drp-1,markedly attenuated the LPS-induced elevation in reactive oxygen species levels and rescued the associated decline in muscle mass.Collectively,these data indicate that LPS-induced muscle mass loss was linked to the reduction of Bacteroidetes abundance,increased inflammation,and the disruption of mitochondrial morphology.These insights offer promising avenues for the identification of potential therapeutic targets aimed at mitigating muscle mass loss.展开更多
文摘Colorectal cancer(CRC)is the third most commonly diagnosed cancer globally and the second cancer in terms of mortality.The prevalence of sarcopenia in patients with CRC ranges between 12%-60%.Sarcopenia comes from the Greek“sarx”for flesh,and“penia”for loss.Sarcopenia is considered a phenomenon of the aging process and precedes the onset of frailty(primary sarcopenia),but sarcopenia may also result from pathogenic mechanisms and that disorder is termed secondary sarcopenia.Sarcopenia diagnosis is confirmed by the presence of low muscle quantity or quality.Three parameters need to be measured:muscle strength,muscle quantity and physical performance.The standard method to evaluate muscle mass is by analyzing the tomographic total cross-sectional area of all muscle groups at the level of lumbar 3rd vertebra.Sarcopenia may negatively impact on the postoperative outcomes of patients with colorectal cancer undergoing surgical resection.It has been described an association between sarcopenia and numerous poor short-term CRC outcomes like increased perioperative mortality,postoperative sepsis,prolonged length of stay,increased cost of care and physical disability.Sarcopenia may also negatively impact on overall survival,disease-free survival,recurrence-free survival,and cancerspecific survival in patients with non-metastatic and metastatic colorectal cancer.Furthermore,patients with sarcopenia seem prone to toxic effects during chemotherapy,requiring dose deescalations or treatment delays,which seems to reduce treatment efficacy.A multimodal approach including nutritional support(dietary intake,high energy,high protein,and omega-3 fatty acids),exercise programs and anabolic-orexigenic agents(ghrelin,anamorelin),could contribute to muscle mass preservation.Addition of sarcopenia screening to the established clinical-pathological scores for patients undergoing oncological treatment(chemotherapy,radiotherapy or surgery)seems to be the next step for the best of care of CRC patients.
基金supported by the National Natural Science Foundation of China(32372925)the Science and Technology Innovation Program of Hunan Province(2022RC1159)+2 种基金the Changsha Natural Science Funds for Distinguished Young Scholar(kq2009020)the National Key Research and Development Programs of China(2022YFD1300503)the China Agriculture Research System of MOF and MARA(CARS35)。
文摘We previously demonstrated that lipopolysaccharide(LPS)injection-induced immune stress could impair muscle growth in weaned piglets,but the precise mechanisms behind this remain elusive.Here,we found that chronic immune stress induced by LPS resulted in a significant reduction of 36.86%in the total muscle mass of piglets at 5 d post-treatment compared with the control group.At 1 d,prior to muscle mass loss,multiple alterations were noted in response to LPS treatment.These included a reduction in the abundance of Bacteroidetes,an increase in serum concentrations of pro-inflammatory cytokines,compromised mitochondrial morphology,and an upregulation in the expression of dynamin-related protein 1(Drp1),a critical protein involved in mitochondrial fission.We highlight a strong negative correlation between Bacteroidetes abundance and the levels of serum pro-inflammatory cytokines,corroborated by in vivo intervention strategies in the musculature of both pig and mouse models.Mechanistically,the effects of Bacteroidetes on inflammation and muscle mass loss may involve the signaling pathway of the tauro-β-muricholic acid-fibroblast growth factor 15.Furthermore,the induction of overexpression of inflammatory cytokines,achieved without LPS treatment through oral administration of recombinant human IL-6(rh IL-6),led to increased levels of circulating cytokines,subsequently causing a decrease in muscle mass.Notably,pre-treatment with Mdivi-1,an inhibitor of Drp-1,markedly attenuated the LPS-induced elevation in reactive oxygen species levels and rescued the associated decline in muscle mass.Collectively,these data indicate that LPS-induced muscle mass loss was linked to the reduction of Bacteroidetes abundance,increased inflammation,and the disruption of mitochondrial morphology.These insights offer promising avenues for the identification of potential therapeutic targets aimed at mitigating muscle mass loss.
