硝黄散外敷联合加味五虎汤口服治疗痰热闭肺型肺炎支原体肺炎患儿对肺功能和血清TNF-α、IFN-γ、IL-4水平的影响

目的:观察硝黄散外敷联合加味五虎汤口服治疗痰热闭肺型肺炎支原体肺炎(MPP)患儿对肺功能和血清肿瘤坏死因子-α(TNF-α)、γ-干扰素(IFN-γ)、白介素-4(IL-4)水平的影响。方法:研究对象为我院2019年6月~2021年1月期间收治的MPP患儿80例,采用随机数字表法将患儿分为对照组(n=40,阿奇霉素抗感染治疗)和研究组(n=40,对照组基础上加用硝黄散外敷联合加味五虎汤口服治疗),均治疗7 d。比较两组患儿临床疗效,比较两组治疗前、治疗7 d后的中医证候积分、临床症状改善情况、肺功能和血清TNF-α、IFN-γ、IL-4水平。结果:研究组治疗7 d后的临床总有效率为92.50%(37/40),高于对照组的72.50%(29/40),差异有统计学意义(P<0.05)。与对照组相比,研究组的症状(咳嗽憋喘、发热、肺部干湿啰音)消失时间均更短(P<0.05)。与对照组相比,研究组治疗7 d后用力肺活量(FVC)、最高呼气峰流速(PEF)、第1秒最大呼气容积(FEV1)、FEV1/FVC均更高(P<0.05),研究组治疗7 d后的中医证候积分及血清TNF-α、IFN-γ和IL-4水平均更低(P<0.05)。结论:痰热闭肺型MPP患儿采用硝黄散外敷联合加味五虎汤口服治疗,可有效缩短患儿症状消失时间,显著改善其肺功能、血清炎症因子水平,疗效显著。     

Leptin improves in-vitro maturation of goat oocytes through MAPK and JAK2/STAT3 pathways and affects gene expression of cumulus cells

We investigated whether the recombinant leptin (1, 10, 100 ng/mL) influences the meiotic maturation of goat oocytes, whether the MAPK and JAK2/STAT3 pathways mediate the effects of leptin during in-vitro maturation, and whether leptin differently affects the abundance of mRNAs relevant to leptin signal transduction and apoptosis in oocytes and cumulus cells. The addition of leptin to the maturation medium positively affected the number of oocytes that completed nuclear maturation. Nuclear oocyte maturation stimulated by leptin was significantly impaired when we added the specific inhibitors of MAPK (U0126) and JAK2/STAT3 (AG490) to the maturation medium. The addition of leptin (10 ng/mL) during maturation did not affect the expression of AMPKα1, PPARα, Caspase 3, and BCL2 genes in oocytes or cumulus cells. The PPARγ and BAX mRNA abundances were significantly reduced in cumulus cells in the leptin group compared to the control group. Our results demonstrate that supplementation of the in-vitro maturation medium with leptin significantly improves nuclear maturation and reveal the important role of the MAPK and JAK2/STAT3 signaling pathways in establishing the leptin-mediated nuclear maturation of goat oocytes. Moreover, leptin treatment affects PPARγ and BAX gene expression in cumulus cells.     

The multifaceted role of TMEM16A in cancer

The calcium-activated chloride channel TMEM16A is intimately linked to cancers. Over decades, TMEM16A over-expression and contribution to prognosis have been widely studied for multiple cancers strengthening the idea that TMEM16A could be a valuable biomarker and a promising therapeutic target. Surprisingly, from the survey of the literature, it appears that TMEM16A has been involved in multiple cancer-related functions and a large number of molecular targets of TMEM16A have been proposed. Thus, TMEM16A appears to be an ion channel with a multifaceted role in cancers.In this review, we summarize the latest development regarding TMEM16A contribution to cancers. We will survey TMEM16A contribution in cancer prognosis, the origins of its over-expression in cancer cells, the multiple biological functions and molecular pathways regulated by TMEM16A. Then, we will consider the question regarding the molecular mechanism of TMEM16A in cancers and the possible basis for the multifaceted role of TMEM16A in cancers.     

Potential roles and targeted therapy of the CXCLs/CXCR2 axis in cancer and inflammatory diseases

The chemokine receptor CXCR2 and its ligands are implicated in the progression of tumours and various inflammatory diseases. Activation of the CXCLs/CXCR2 axis activates multiple signalling pathways, including the PI3K, p38/ERK, and JAK pathways, and regulates cell survival and migration. The CXCLs/CXCR2 axis plays a vital role in the tumour microenvironment and in recruiting neutrophils to inflammatory sites. Extensive infiltration of neutrophils during chronic inflammation is one of the most important pathogenic factors in various inflammatory diseases. Chronic inflammation is considered to be closely correlated with initiation of cancer. In addition, immunosuppressive effects of myeloid-derived suppressor cells (MDSCs) against T cells attenuate the anti-tumour effects of T cells and promote tumour invasion and metastasis. Over the last several decades, many therapeutic strategies targeting CXCR2 have shown promising results and entered clinical trials. In this review, we focus on the features and functions of the CXCLs/CXCR2 axis and highlight its role in cancer and inflammatory diseases. We also discuss its potential use in targeted therapies.     

Synthetic biology and metabolic engineering of actinomycetes for natural product discovery

Actinomycetes are one of the most valuable sources of natural products with industrial and medicinal importance. After more than half a century of exploitation, it has become increasingly challenging to find novel natural products with useful properties as the same known compounds are often repeatedly re-discovered when using traditional approaches. Modern genome mining approaches have led to the discovery of new biosynthetic gene clusters, thus indicating that actinomycetes still harbor a huge unexploited potential to produce novel natural products. In recent years, innovative synthetic biology and metabolic engineering tools have greatly accelerated the discovery of new natural products and the engineering of actinomycetes. In the first part of this review, we outline the successful application of metabolic engineering to optimize natural product production, focusing on the use of multi-omics data, genome-scale metabolic models, rational approaches to balance precursor pools, and the engineering of regulatory genes and regulatory elements. In the second part, we summarize the recent advances of synthetic biology for actinomycetal metabolic engineering including cluster assembly, cloning and expression, CRISPR/Cas9 technologies, and chassis strain development for natural product overproduction and discovery. Finally, we describe new advances in reprogramming biosynthetic pathways through polyketide synthase and non-ribosomal peptide synthetase engineering. These new developments are expected to revitalize discovery and development of new natural products with medicinal and other industrial applications.     

PTPN2 induced by inflammatory response and oxidative stress contributed to glioma progression

Malignant glioma remains the most frequent form of primary brain tumors all over the world. The gliomagenesis is characterized by various molecular processes such as neoplastic transformation, dysregulation of the cell cycle, and angiogenesis. Among these biomolecular events, the existence of inflammation and oxidative stress pathways in the development of glioma has been reported. PTPN2 is associated with several inflammatory disorders. However, the biological role of PTPN2 in inflammation responses and oxidative stress pathways involved in glioma remains poorly known. Here, we focused on its function in glioma development. Here, we observed that PTPN2 was significantly increased in glioma especially in a grade-dependent manner. Meanwhile, interferon-γ and tumor necrosis factor-α, which have been identified as crucial inflammation cytokines, were able to trigger PTPN2 expression in a dose-dependent course in T98G cells. Then, we found that PTPN2 was oxidated and inactivated by H₂O₂. Meanwhile, H₂O₂ induced glioma cell colony formation capacity and increased ki-67 expression confirmed by flow cytometry assay. Finally, T98G cells were transfected with PTPN2 shRNA and it was shown that knockdown of PTPN2 obviously inhibited T98G cell colony formation and induced cell apoptosis. In summary, our findings indicated that PTPN2 could be induced by inflammatory response and oxidative stress and its deficiency depressed glioma cell growth.