肠道微生物群衍生的代谢产物调控结直肠癌的新进展

肠道生态系统的改变会影响人类的健康,甚至引发结直肠癌。大量证据表明,在结直肠癌患者的肠道中普遍存在一种病理性微生物群失衡状态,失衡的微生物群衍生的代谢产物也会影响结直肠癌的发生发展。本文综述了由特定肠道微生物群代谢产物触发结直肠癌进程的方式,总结了肠道微生物群代谢产物对结直肠癌贡献的最新进展,并考虑代谢产物的积累效应以及多种代谢产物相结合的方式来预测和预防结直肠癌。     

CTRP4 acts as an anti-inflammatory factor in macrophages and protects against endotoxic shock

Despite the availability of antibiotics, current therapies to treat sepsis are still ineffective and many clinical trials aimed at neutralizing specific inflammatory cytokines have failed, suggesting the urgent need for new treatments. Using two models of LPS-induced endotoxemia and cecal ligation and puncture (CLP)–induced sepsis, we investigated the effects of C1q/TNF-related protein 4(CTRP4) on septic lethality and sepsis-induced inflammation. The effects of CTRP4 on survival, inflammation, organ damage, and bacterial clearance were assessed. Here, we found that CTRP4 decreased the mortalities of mice and alleviated pathological lung injury in mice model. In vivo depletion and adoptive transfer studies showed CTRP4-expressing macrophages as the key cell type inhibiting LPS-induced septic shock. The mechanism associated with the CTRP4 deficiency involved promoting of TLR4 internalization and activation of downstream pathways that resulted in a lethal, prolonged proinflammatory cytokine storm. Treatment of macrophages with exogenous CTRP4 abrogated proinflammatory cytokine production. Our results showed CTRP4 regulates inflammatory response and could be a promising strategy to treat septic shock.     

Chimeric antigen receptor-modified human regulatory T cells that constitutively express IL-10 maintain their phenotype and are potently suppressive

Clinical trials of Treg therapy in transplantation are currently entering phases IIa and IIb, with the majority of these employing polyclonal Treg populations that harbor a broad specificity. Enhancing Treg specificity is possible with the use of chimeric antigen receptors (CARs), which can be customized to respond to a specific human leukocyte antigen (HLA). In this study, we build on our previous work in the development of HLA-A2 CAR-Tregs by further equipping cells with the constitutive expression of interleukin 10 (IL-10) and an imaging reporter as additional payloads. Cells were engineered to express combinations of these domains and assessed for phenotype and function. Cells expressing the full construct maintained a stable phenotype after transduction, were specifically activated by HLA-A2, and suppressed alloresponses potently. The addition of IL-10 provided an additional advantage to suppressive capacity. This study therefore provides an important proof-of-principle for this cell engineering approach for next-generation Treg therapy in transplantation.     

Interleukin-34 accelerates intrauterine adhesions progress related to CX3CR1+ monocytes/macrophages

Intrauterine adhesions (IUA) are characterized by endometrial fibrosis and impose a great challenge for female reproduction. IL-34 is profoundly involved in various fibrotic diseases through regulating the survival, proliferation, and differentiation of monocytes/macrophages. However, it remains unclear how IL-34 regulates monocytes/macrophages in context of IUA. Here, we showed that the expression level of IL-34 and the amount of CX3CR1+ monocytes/macrophages were significantly increased in endometrial tissues of IUA patients. IL-34 promoted the differentiation of monocytes/macrophages, which express CX3CR1 via CSF-1R/P13K/Akt pathway in vitro. Moreover, IL-34-induced CX3CR1+ monocytes/macrophages promoted the differentiation of endometrial stromal cells into myofibroblasts. Of note, IL-34 caused endometrial fibrosis and increased the amount of CX3CR1+ monocytes/macrophages in endometrial tissues in vivo. IL-34 modulated endometrial fibrosis by regulating monocytes/macrophages since the elimination of endometrial monocytes/macrophages significantly suppressed the profibrotic function of IL-34. Finally, blocking of IL-34 in the LPS-IUA model resulted in the improvement of endometrial fibrosis and decreased number of CX3CR1+ monocytes/macrophages. Our studies uncover the novel mechanism of interaction between IL-34-induced CX3CR1+ monocytes/macrophages and endometrial stromal cells in endometrial fibrosis pathogenesis, and highlight IL-34 as a critical target for treating IUA.     

C-di-GMP turnover influences motility and biofilm formation in Bacillus amyloliquefaciens PG12

Bis-(3′→5′) cyclic dimeric guanosine monophosphate (c-di-GMP) is defined as a highly versatile secondary messenger in bacteria, coordinating diverse aspects of bacterial growth and behavior, including motility and biofilm formation. Bacillus amyloliquefaciens PG12 is an effective biocontrol agent against apple ring rot caused by Botryosphaeria dothidea. In this study, we characterized the core regulators of c-di-GMP turnover in B. amyloliquefaciens PG12. Using bioinformatic analysis, heterologous expression and biochemical characterization of knockout and overexpression derivatives, we identified and characterized two active diguanylate cyclases (which catalyze c-di-GMP biosynthesis), YhcK and YtrP and one active c-di-GMP phosphodiesterase (which degrades c-di-GMP), YuxH. Furthermore, we showed that elevating c-di-GMP levels up to a certain threshold inhibited the swimming motility of B. amyloliquefaciens PG12. Although yhcK, ytrP and yuxH knockout mutants did not display defects in biofilm formation, significant increases in c-di-GMP levels induced by YtrP or YuxH overexpression stimulated biofilm formation in B. amyloliquefaciens PG12. Our results indicate that B. amyloliquefaciens possesses a functional c-di-GMP signaling system that influences the bacterium's motility and ability to form biofilms. Since motility and biofilm formation influence the efficacy of biological control agent, our work provides a basis for engineering a more effective strain of B. amyloliquefaciens PG12.     

少数民族边远地区医学院校硕士研究生导师队伍的管理与思考

目的 分析地处广西少数民族边远地区的某医学院硕士研究生导师队伍的建设与管理现状，研究其硕士生导师队伍建设与管理过程中存在的主要问题。方法 参考国家和学校有关研究生教育管理文件和硕士研究生导师遴选、培养和管理等规章制度以及相关文献设计调查问卷，选取右江民族医学院66 名硕士研究生导师进行调查。结果 49.13% 的导师认为学术型导师遴选条件中对科研成果、教学成果或其他成果的要求欠合理，38.60% 的导师认为专业型导师遴选条件中对主持课题及经费的要求不合理，29.82% 的导师认为专业型导师遴选条件中对学历、职称和临床实践工作时间的要求欠合理；对其他遴选条件要求的认可程度均在80% 以上；但有50.87% 的导师认为遴选条件存在标准量化不够等问题。5 年来有超过30% 的导师未单次外出学习（进修）超过3 个月，54.40% 的导师参加导师培训的次数不超过1 次，50.87% 的导师未参与制定本学科、专业研究生培养方案。85.97% 的导师认为每人每届指导的研究生不宜超过2 人。80.70% 的导师认为应该对硕导进行科研方法的培训。68.42% 的导师对学校的导师考核和评价制度不满意。结论 当前硕士生导师队伍管理还存在一些不足，相关管理体系有待进一步改革与完善。     

Sixteen Chinese pediatric brucellosis patients onset of fever in non-epidemic areas and 8 developed with osteoarticular involvement

The purpose of this study is to summarize the manifestations, diagnosis, differential diagnosis, and treatment of childhood brucellosis in non-epidemic areas of China. A retrospective review of 16 admitted children patients with brucella’s disease who were diagnosed of brucellosis during the period from 2011 to 2016 was performed. Diagnostic criteria, clinical presentations, and outcomes were recorded. The most common symptom was fever. Osteoarticular involvement was found in 50% of the patients. They were infected by contacting with infected animals or consuming of unpasteurized milk or meat of sheep or goats, also. Standard agglutination test was positive in all patients and blood culture in 10 (62.5%) patients as well as medulloculture in 3 (18.8%) patients were positive. A combination of antibiotic treatment with rifampin plus cotrimoxazole showed good response and all clinical manifestations improved. Brucellosis is misdiagnosed frequently and should be considered in the differential diagnosis when patients do not respond to standard treatment. Blood culture, together with brucella serology test, is important and helpful in the diagnosis. MRI is a good method in differentiating those with symptoms of arthritis.     

Adipose-derived stem cells promote tumor initiation and accelerate tumor growth by interleukin-6 production

Adipose-derived stem cells (ADSCs) are multipotent cells that have attracted much recent attention. Here, we show that ADSCs enhance sphere formation and in vivo tumor initiation of breast and colon cancer cells. In co-culture, ADSCs induced several stem cell markers in cancer cells. ADSCs also accelerated tumor growth. Interaction of ADSCs and cancer cells stimulated secretion of interlukin-6 in ADSCs, which in turn acted in a paracrine manner on cancer cells to enhance their malignant properties. Interleukin-6 regulated stem cell-related genes and activated JAK2/STAT3 in cancer cells. We suggest that ADSCs may enhance tumor initiation and promotion.