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Biomedicine & pharmacotherapy
Masson Pub. USA, Inc.
Biomedicine & pharmacotherapy

Masson Pub. USA, Inc.

0753-3322

Biomedicine & pharmacotherapy/Journal Biomedicine & pharmacotherapySCIISTP
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    Exploiting systems biology to investigate the gene modules and drugs in ovarian cancer: A hypothesis based on the weighted gene co-expression network analysis

    Samira NomiriHassan KaramibBehzad BaradaranDarya Javadrashid...
    1页
    查看更多>>摘要：Background: Ovarian cancer (OC) is one of the worrisome gynecological cancers worldwide. Given its considerable mortality rate, it is necessary to investigate its oncogenesis. Methods: In this study, we used systems biology approaches to describe the key gene modules, hub genes, and regulatory drugs associated with serous OC as the novel biomarkers using weighted gene co-expression network analysis (WGCNA). Findings: Our findings have demonstrated that the blue module genes (r = 0.8, p-value = 1e-16) are involved in OC progression. Based on gene enrichment analysis, the genes in this module are frequently involved in biological processes such as the Cyclic adenosine monophosphate (cAMP) signaling pathway and the cellular response to transforming growth factor-beta stimulation. The co-expression network has been built using the correlated module's top hub genes, which are ADORA1, ANO9, CD24P4, CLDN3, CLDN7, ELF3, KLHL14, PRSS8, RASAL1, RIPK4, SERINC2, and WNT7A. Finally, a drug-target network has been built to show the interaction of the FDA-approved drugs with hub genes. Conclusions: Our results have discovered that ADORA1, ANO9, SERINC2, and KLHL14 are hub genes associated with serous OC. These genes can be considered as novel candidate target genes for treating OC.
      原文链接:
    • NSTL

    Traditional Chinese medicine enhances myocardial metabolism during heart failure

    Wang Shao-meiYe Li-fangWang Li-hong
    1页
    查看更多>>摘要：The prognosis of various cardiovascular diseases eventually leads to heart failure (HF). An energy metabolism disorder of cardiomyocytes is important in explaining the molecular basis of HF; this will aid global research regarding treatment options for HF from the perspective of myocardial metabolism. There are many drugs to improve myocardial metabolism for the treatment of HF, including angiotensin receptor blocker-neprilysin inhibitor (ARNi) and sodium glucose cotransporter 2 (SGLT-2) inhibitors. Although Western medicine has made considerable progress in HF therapy, the morbidity and mortality of the disease remain high. Therefore, HF has attracted attention from researchers worldwide. In recent years, the application of traditional Chinese medicine (TCM) in HF treatment has been gradually accepted, and many studies have investigated the mechanism whereby TCM improves myocardial metabolism; the TCMs studied include Danshen yin, Fufang Danshen dripping pill, and Shenmai injection. This enables the clinical application of TCM in the treatment of HF by improving myocardial metabolism. We systematically reviewed the efficacy of TCM for improving myocardial metabolism during HF as well as the pharmacological effects of active TCM ingredients on the cardiovascular system and the potential mechanisms underlying their ability to improve myocardial metabolism. The results indicate that TCM may serve as a complementary and alternative approach for the prevention of HF. However, further rigorously designed randomized controlled trials are warranted to assess the effect of TCM on long-term hard endpoints in patients with cardiovascular disease.
      原文链接:
    • NSTL

    Amphibian-derived peptide homodimer promotes regeneration of skin wounds

    Yinglei WangZhe FuLongjun ShuYixiang Liu...
    1页
    查看更多>>摘要：Despite the increasing treatments in skin wound repair, existing therapeutic drugs cannot meet current needs. As such, skin wound repair remains a considerable clinical challenge, and thus the discovery of new pro-healing agents is crucial. Here, we identified the first naturally occurring peptide homodimer named as OA-GP11 dimer (OA-GP11d) from Odorrana andersonii (odorous frog) through the combinational methods of peptido-mics and genomics. OA-GP11d was linked by the intramolecular disulfide formed by the 10~th cysteine residues from the monomer of peptide with sequence of GPLSGINAECM, which effectively promoted the repair of full-thickness and burn wounds in mice. The underlying molecular mechanisms revealed that OA-GP11d not only accelerated the migration and cell-scratch healing of mouse keratinocytes, but also activated the mitogen-activated protein kinases (MAPKs) signaling pathway (phosphorylation of p38 and ERK subgroups) in immortalized human keratinocytes (HaCaT). Besides, OA-GP11d reduced the phosphorylation of nuclear factor-κB (NF-κB) and inhibitor of NF-κB (I-κB) induced by lipopolysaccharide stimulation in mouse macrophages, and inhibited the release of associated inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6. OA-GP11d is the first identified naturally occurring peptide dimer with significant pro-healing potency. Our results highlight the importance of amphibians as a source of novel pro-healing agents and suggest OA-GP11d as a potential new pro-regenerative drug candidate.
      原文链接:
    • NSTL

    Are the functions of milk exosomes restricted to their protein cargoes?

    Elrashdy M. RedwanVladimir N. Uversky
    1页
    查看更多>>摘要：Numerous studies have analyzed the benefits of camel milk health over human and bovine milk. These health benefits range from broad antimicrobial and antiviral potentials to anti-cancer activity and capability to act as anti-diabetics. The milk ingredients behind these benefits are variable and can be changed depending on the lactation season. To explore which components are responsible for these benefits, reports are often focused on the analysis of various biological macro-molecules, but most studies are concentrated on the milk proteome analysis, whereas many other important biomolecules that can be found in milk, such as RNA, polysaccharides, and/or lipids, are mostly ignored in such proteome-centric studies. Noticeable variations are also observed between different studies, with outputs showing strong dependence on the evaluation methods used. Furthermore, recent studies become increasingly focused on the analysis of extracellular vesicles (EVs), such as milk fat globules (MFGs) and/or exosomes, rather than at the entire set of milk constituents. A recently published article by El-kattawy et al. represents an example of such a protein-centric study, where the authors ascribed the in vitro anti-cancer effects of the exosomes extracted from camel milk to the lactoferrin and κ-casein proteins.
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    • NSTL

    The potential use of folate and its derivatives in treating psychiatric disorders: A systematic review

    Nelson Siu Kei LamXin Xin LongXuegang LiMirette Saad...
    1页
    查看更多>>摘要：Objectives: To examine the strengths and limitations of existing data to provide guidance for the use of folate supplements as treatment, with or without other psycho tropic medications, in various psychiatric disorders. To identify area for further research in terms of the biosynthesis of mechanism of folate and genetic variants in metabolic pathway in human. Methods: A systematic review of published literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to assess whether folate supplements are beneficial in certain psychiatric disorders (depression, bipolar disorder, schizophrenia, autism spectrum disorder, and attention deficit hyperactivity disorder). Methodology of this review is registered with Prospero (Registration number CRD 42021266605). Data sources: Eligible studies were identified using a systematic search of four electronic databases: Embase, Pubmed, PsycINFO, and Cochrane. The search strategy covered the time period from 1974 to August 16th, 2021. Therefore, this review examines randomized control trials or open-label trials completed during this period. Results: We identified 23 studies of folate supplements in various psychiatric disorders for critical review. Of these, 9 studies investigated the efficacy of folate supplements in major depressive disorders, 5 studies in schizophrenia, 6 studies in autism spectrum disorder, 2 studies in bipolar affective disorder and 1 study in attention deficit hyperactive disorder. The most consistent finding association of oral levomefolic acid or 5-meth-ylfolate with improvement in clinical outcomes in mental health conditions as mentioned above, especially in major depressive disorder (including postpartum and post-menopausal depression), schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder and bipolar affective disorder. Folate supplements were well tolerated. Limitation: Our results are not representative of all types of studies such as case reports or case series studies, nor are they representative of the studies conducted in languages that are not in English or not translated in English. Conclusion: Increasing evidence from clinical trials consistently demonstrate folate supplements, especially levomefolic acid or 5-methylfolate, may improve clinical outcomes for certain psychiatric diseases, especially as an adjunct pharmacotherapy with minimal side effects.
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    • NSTL

    Traditional Chinese medicine for precancerous lesions of gastric cancer: A review

    Weichao XuBolin LiMiaochan XuTianxiao Yang...
    1页
    查看更多>>摘要：Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of death due to cancer worldwide. The gastric mucosa often undergoes many years of precancerous lesions of gastric cancer (PLGC) stages before progressing to gastric malignancy. Unfortunately, there are no effective Western drugs for patients with PLGC. In recent years, traditional Chinese medicine (TCM) has been proven effective in treating PLGC. Classical TCM formulas and chemical components isolated from some Chinese herbal medicines have been administered to treat PLGC, and the main advantage is their comprehensive intervention with multiple approaches and multiple targets. In this review, we focus on recent studies using TCM treatment for PLGC, including clinical observations and experimental research, with a focus on targets and mechanisms of drugs. This review provides some ideas and a theoretical basis for applying TCM to treat PLGC and prevent GC.
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    • NSTL

    Mesalazine initiates an anti-oncogenic β-catenin / MUCDHL negative feed-back loop in colon cancer cells by cell-specific mechanisms

    Emilie BersuderChloe TercioloMathilde LechevrelElisabeth Martin...
    1页
    查看更多>>摘要：Chronic inflammation associated with intestinal architecture and barrier disruption puts patients with inflammatory bowel disease (IBD) at increased risk of developing colorectal cancer (CRC). Widely used to reduce flares of intestinal inflammation, 5-aminosalicylic acid derivatives (5-ASAs) such as mesalazine appear to also exert more direct mucosal healing and chemopreventive activities against CRC. The mechanisms underlying these activities are poorly understood and may involve the up-regulation of the cadherin-related gene MUCDHL (CDHR5). This atypical cadherin is emerging as a new actor of intestinal homeostasis and opposes colon tumorigenesis. Here, we showed that mesalazine increase mRNA levels of MUCDHL and of other genes involved in the intestinal barrier function in most intestinal cell lines. In addition, using gain / loss of function experiments (agonists, plasmid or siRNAs transfections), luciferase reporter genes and chromatin immunoprecipitation, we thoroughly investigated the molecular mechanisms triggered by mesalazine that lead to the up-regulation of MUCDHL expression. We found that basal transcription of MUCDHL in different CRC cell lines is regulated positively by CDX2 and negatively by β-catenin through a negative feed-back loop. However, mesalazine-stimulation of MUCDHL transcription is controlled by cell-specific mechanisms, involving either enhanced activation of CDX2 and PPAR-γ or repression of the β-catenin inhibitory effect. This work highlights the importance of the cellular and molecular context in the activity of mesalazine and suggests that its efficacy against CRC depends on the genetic alterations of transformed cells.
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    The expression and function of miR-622 in a variety of tumors

    Juan LuZhongyang XieZhaoying XiaoDanhua Zhu...
    1页
    查看更多>>摘要：Cancer is a heavy burden worldwide, with high morbidity and mortality rates. Cancer treatments currently involve surgical and nonsurgical approaches. Molecular targeted therapy is the latest breakthrough. miRNAs are small noncoding RNAs found in plants and animals that play a role in cancer and various diseases through influencing numerous biological processes, such as cell proliferation, apoptosis, the immune response, and drug resistance. One miRNA, miR-622, has been shown to regulate various pathways to influence disease processes. Abnormal miR-622 expression can promote or inhibit liver, colorectal, and breast cancers and other tumors, such as glioma. Herein, we reviewed the expression levels and clinical effects of miR-622 in various tumors and summarized its mechanisms and related molecules.
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    • NSTL

    Polyphenols inhibiting MAPK signalling pathway mediated oxidative stress and inflammation in depression

    Maaz NaqviAayush SehgalSukhbir SinghNeelam Sharma...
    1页
    查看更多>>摘要：Depression is one of the most debilitating psychiatric disorders affecting people of all ages worldwide. Despite significant heterogeneity between studies, increased inflammation and oxidative stress have been found in depression. Oxidative stress and inflammation are involved in the pathogenesis of depression. In the current review, we discussed the markers of oxidative stress and inflammation in depressive disorder and the association between these markers and the antidepressant treatment. The role of natural polyphenols in regulating various cell signaling pathways related to oxidative stress and inflammation has also been reviewed. The inhibitory effect of polyphenols on several cell signaling pathways reveals the vital role of polyphenols in the prevention and treatment of depressive disorder. Understanding the mechanism of polyphenols implicated in the regulation of cell signaling pathways is essential for the identification of lead compounds and the development of novel effective compounds for the prevention and treatment of depressive disorder.
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    • NSTL

    Plumbagin reduction by thioredoxin reductase 1 possesses synergy effects with GLUT1 inhibitor on KEAP1-mutant NSCLC cells

    Shibo SunYue ZhangWeiping XuRui Yang...
    1页
    查看更多>>摘要：Thioredoxin reductase 1 (TrxR1 or TXNRD1) is a major enzyme in cellular redox regulation and is considered as a drug target for cancer therapy. Previous studies have reported that plumbagin caused reactive oxygen species (ROS)-dependent apoptosis via inhibiting TrxR1 activity or being reduced by TrxR1, leading to selectively cancer cell death. However, the mechanism of TrxR1-mediated redox cycling of plumbagin is obscure and the evidence for plumbagin targeting TrxR1 is still lacking. Herein, we demonstrated that TrxR1 catalyzed plumbagin reduction in both selenocysteine (Sec)-dependent and independent manners, and its activity relied on the intact N-terminal motif of TrxR1, but a high-efficiency reduction was supported by the C-terminal thiols. During the redox cycling of plumbagin, excessive ROS production was observed coupled with oxygen. Using LC-MS and TrxR1 mutants, we found that the Sec residue of TrxR1 was modified by plumbagin, which converted the enzyme from antioxidant to pro-oxidant. Furthermore, we evaluated the therapeutic potential of plumbagin in non-small cell lung cancer (NSCLC), and found that Kelch-like ECH-associated protein 1 (KEAP1)-mutant NSCLC cells, which possess constitutive nuclear factor erythroid 2-related factor 2 (NRF2) activity, were insensitive to plumbagin; however, inhibition of glucose transporter 1 (GLUT1) by small-molecule BAY-876 or inhibiting glucose-6-phosphate dehydrogenase (G6PD) by 6-aminonicotinamide (6-AN) overcame the plumbagin-resistance of KEAP1-mutant NSCLC cells. Taken together, this study elucidated the pharmacological mechanism of plumbagin by targeting TrxR1 and revealed the synergy effect of plumbagin and BAY-876, which may be helpful for applying naphthoquinone compounds to chemotherapy, particularly for treating KEAP1-mutant NSCLC cells.
      原文链接:
    • NSTL