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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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    Dual role of microbiota-derived short-chain fatty acids on host and pathogen

    Rasoul MirzaeiElahe DehkhodaieBehnaz BouzariMana Rahimi...
    1页
    查看更多>>摘要：A growing body of documents shows microbiota produce metabolites such as short-chain fatty acids (SCFAs) as crucial executors of diet-based microbial influence the host and bacterial pathogens. The production of SCFAs depends on the metabolic activity of intestinal microflora and is also affected by dietary changes. SCFAs play important roles in maintaining colonic health as an energy source, as a regulator of gene expression and cell differentiation, and as an anti-inflammatory agent. Additionally, the regulated expression of virulence genes is critical for successful infection by an intestinal pathogen. Bacteria rely on sensing environmental signals to find preferable niches and reach the infectious state. This review will present data supporting the diverse functional roles of microbiota-derived butyrate, propionate, and acetate on host cellular activities such as immune modulation, energy metabolism, nervous system, inflammation, cellular differentiation, and anti-tumor effects, among others. On the other hand, we will discuss and summarize data about the role of these SCFAs on the virulence factor of bacterial pathogens. In this regard, receptors and signaling routes for SCFAs metabolites in host and pathogens will be introduced.
      原文链接:
    • NSTL

    Glyphaeaside C- enriched extract of Glyphaea brevis restored the antioxidant and reproductive integrity of 1,4-Dinitrobenzene-intoxicated rats

    Janet Olayemi OlugbodiMary Tolulope OlaleyeGomaa Mostafa-HedeabMohammed Alqarni...
    1页
    查看更多>>摘要：This study assessed the fertility potential of methanol leaf extract of Glyphaea brevis (MGB) in rats exposed to 1,4-Dinitrobenzene (DNB), an environmental reprotoxicant. Male Wistar rats were orally exposed to 50 mg/kg DNB and administered 750 mg/kg MGB, 1500 mg/kg MGB or 300 mg/kg vitamin E for 21 days after 48 h of DNB exposure. Determination of serum reproductive hormone levels by enzyme-linked immunosorbent assays, evaluation of hematologic profile, computer-assisted sperm analyses (CASA) of sperm kinematics and morphology, assessment of testicular and spermatozoan antioxidant systems, and histopathological evaluation of reproductive tissues were performed. HPLC-DAD analysis identify Glyphaeaside C as the major component of the extract. In rats toxified with 50 mg/kg DNB, testicular and epididymal weights, serum levels of luteinizing hormone, testosterone and follicle-stimulating hormone, and packed cell volume, haemoglobin concentration, and white blood cell counts were decreased. There was altered sperm kinematics which reflected in increased sperm abnormalities. Treatment with the Glyphaeaside C -enriched MGB counteracted all DNB-induced changes and corrected DNB-induced aberrations in kinematic endpoints. Also, testicular and epididymal antioxidant systems were disrupted and there was damage to tissue histoarchitecture. Furthermore, our molecular docking study revealed that Glyphaeaside-C exhibited high binding affinities to the binding pocket of some free radical generating enzymes. Conclusively, the results indicated that Glyphaeaside C-enriched extract of Glyphaea brevis leaf enhanced the quality of semen and improved the functional capabilities of spermatozoa following exposure of rats to DNB which could translate to enhanced fertility.
      原文链接:
    • NSTL

    Abnormal cannabidiol ameliorates inflammation preserving pancreatic beta cells in mouse models of experimental type 1 diabetes and beta cell damage

    Isabel Gonzalez-MariscalMacarena Pozo-MoralesSilvana Y. Romero-ZerboVanesa Espinosa-Jimenez...
    1页
    查看更多>>摘要：The atypical cannabinoid Abn-CBD improves the inflammatory status in preclinical models of several pathologies, including autoimmune diseases. However, its potential for modulating inflammation in autoimmune type 1 diabetes (T1D) is unknown. Herein we investigate whether Abn-CBD can modulate the inflammatory response during T1D onset using a mouse model of T1D (non-obese diabetic- (NOD)-mice) and of beta cell damage (streptozotocin (STZ)-injected mice). Six-week-old female NOD mice were treated with Abn-CBD (0.1-1 mg/kg) or vehicle during 12 weeks and then euthanized. Eight-to-ten-week-old male C57Bl6/J mice were pre-treated with Abn-CBD (1 mg/kg of body weight) or vehicle for 1 week, following STZ challenge, and euthanized 1 week later. Blood, pancreas, pancreatic lymph nodes (PLNs) and T cells were collected and processed for analysis. Glycemia was also monitored. In NOD mice, treatment with Abn-CBD significantly reduced the severity of insulitis and reduced the pro-inflammatory profile of CD4~+ T cells compared to vehicle. Concomitantly, Abn-CBD significantly reduced islet cell apoptosis and improved glucose tolerance. In STZ-injected mice, Abn-CBD decreased circulating proinflammatory cytokines and ameliorated islet inflammation reducing intra-islet phos-pho-NF-κB and TXNIP. Abn-CBD significantly reduced 2 folds intra-islet CD8~+ T cells and reduced Th1/non-Th1 ratio in PLNs of STZ-injected mice. Islet cell apoptosis and intra-islet fibrosis were also significantly reduced in Abn-CBD pre-treated mice compared to vehicle. Altogether, Abn-CBD reduces circulating and intra-islet inflammation, preserving islets, thus delaying the progression of insulitis. Hence, Abn-CBD and related compounds emerge as new candidates to develop pharmacological strategies to treat the early stages of T1D.
      原文链接:
    • NSTL

    Mechanism of Infantile Feire Kechuan Oral Solution against Mycoplasma pneumoniae infection of A549 cells

    Haiwei DouPeng TuDawei ShiQing Yuan...
    1页
    查看更多>>摘要：Background: Mycoplasma pneumoniae is a leading cause of community-acquired respiratory infections. Infantile Feire Kechuan Oral Solution (IFKOS) is effective for treatment of M. pneumoniae infection. The aim of this study was to explore the potential mechanism of IFKOS against M. pneumoniae infection in basal epithelial human lung adenocarcinoma A549 cells. Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to determine the effects of IFKOS on the viability of A549 cells infected with M. pneumoniae. Optical microscopy was used to observe cell morphology and a Muse cell analyzer was used to assess apoptosis and the cell cycle phase. Enzyme-linked immunosorbent assays were employed to assess the expression levels of interleukin (IL)-4, IL-6, IL-8, IL-17, tumor necrosis factor (TNF)-α, interferon (IFN)-α, and IFN-γ. Results: Under certain conditions, M. pneumoniae infection reduced the viability and inhibited the proliferation of A549 cells, promoted early apoptosis, and arrested cells in the G0/G1 phase, thus shortening the S and G2/M phases (allp < 0.05). M. pneumoniae also upregulated expression of IL-8 and TNF-α and downregulated that of IL-6 (p < 0.05), which switched the immune balance of Th1/Th2 to Th1 cells. IFKOS (5.531 mg/mL) improved the viability and proliferation of M. pneumoniae-infected A549 cells, mitigated early apoptosis, and reversed cell cycle arrest in the G0/G1 phase, thereby extending the S and G2/M phases (all,p < 0.05). IFKOS downregulated expression of IL-8 and TNF-α and upregulated that of IL-6 (p < 0.01), thereby reversing the immune imbalance of Th1/Th2. Secretion of IL-4, IL-17, IFN-α, and IFN-γ was not observed. Conclusion: IFKOS played a protective role in the regulation of cell viability, apoptosis, the cell cycle, and Th1/ Th2 immune imbalance induced by M. pneumoniae infection and conveyed an anti-inflammatory effect in A549 cells.
      原文链接:
    • NSTL

    Tongxinluo prevents chronic obstructive pulmonary disease complicated with atherosclerosis by inhibiting ferroptosis and protecting against pulmonary microvascular barrier dysfunction

    Huixin LiZhen LiYi LiuYuanjie Hao...
    1页
    查看更多>>摘要：Cardiovascular comorbidities are pervasive in chronic obstructive pulmonary disease (COPD) and often result in serious adverse cardiovascular events. Tongxinluo (TXL) has been clinically verified to treat atherosclerosis (AS), improve lung function and alleviate dyspnoea. The present study aimed to explore the effect of lung micro-vascular barrier dysfunction on AS in COPD and the potential pulmonary protective mechanisms of TXL in COPD complicated with AS. COPD complicated with AS was induced in mice by cigarette smoke (CS) exposure and high-fat diet (HFD) feeding. The mice were treated with atorvastatin (ATO), TXL or combination therapy (ATO+TXL) for 20 weeks. Pulmonary function, lung pathology, serum lipid levels, atherosclerotic plaque area and indicators of barrier function, oxidative stress and ferroptosis in lung tissue were evaluated. In vitro, human pulmonary microvascular endothelial cells (HPMECs) were pretreated with TXL for 4 h and then incubated with cigarette smoke extract (CSE) and homocysteine (Hcy) for 36 h to induce barrier dysfunction. Then the indicators of barrier function, oxidative stress and ferroptosis were measured. The results demonstrate that CS aggravated dyslipidaemia, atherosclerotic plaque formation, pulmonary function decline, pathological injury, barrier dysfunction, oxidative stress and ferroptosis in the HFD-fed mice. However, these abnormalities were partially reversed by ATO and TXL. Similar results were observed in vitro. In conclusion, pulmonary microvascular barrier dysfunction plays an important role by which COPD affects the progression of AS, and ferroptosis may be involved. Moreover, TXL delays the progression of AS and reduces cardiovascular events by protecting the pulmonary microvascular barrier and inhibiting ferroptosis.
      原文链接:
    • NSTL

    Protein arginine N-methyltransferase 5 in colorectal carcinoma: Insights into mechanisms of pathogenesis and therapeutic strategies

    Wafaa AbumustafaBatoul Abi ZamerBariaa A. KhalilMawieh Hamad...
    1页
    查看更多>>摘要：Protein arginine N-methyltransferase 5 (PRMT5) enzyme is one of the eight canonical PRMTs, classified as a type II PRMT, induces arginine monomethylation and symmetric dimethylation. PRMT5 is known to be overexpressed in multiple cancer types, including colorectal cancer (CRC), where its overexpression is associated with poor survival. Recent studies have shown that upregulation of PRMT5 induces tumor growth and metastasis in CRC. Moreover, various novel PRMT5 inhibitors tested on CRC cell lines showed promising anticancer effects. Also, it was suggested that PRMT5 could be a valid biomarker for CRC diagnosis and prognosis. Hence, a deeper understanding of PRMT5-mediated CRC carcinogenesis could provide new avenues towards developing a targeted therapy. In this study, we started with in silico analysis correlating PRMT5 expression in CRC patients as a prelude to further our investigation of its role in CRC. We then carried out a comprehensive review of the scientific literature that dealt with the role(s) of PRMT5 in CRC pathogenesis, diagnosis, and prognosis. Also, we have summarized key findings from in vitro research using various therapeutic agents and strategies directly targeting PRMT5 or disrupting its function. In conclusion, PRMT5 seems to play a significant role in the pathogenesis of CRC; therefore, its prognostic and therapeutic potential merits further investigation.
      原文链接:
    • NSTL

    Silencing tumor-intrinsic CD73 enhances the chemosensitivity of NSCLC and potentiates the anti-tumoral effects of cisplatin: An in vitro study

    Elham BaghbaniSaeed NoorolyaiShima RahmaniDariush Shanehbi...
    1页
    查看更多>>摘要：Aims: Besides suppressing anti-tumoral immune responses, tumor-intrinsic inhibitory immune checkpoints have been implicated in tumor development. Herein, we aimed to investigate the significance of tumor-intrinsic CD73, as an inhibitory immune checkpoint, in non-small cell lung cancer (NSCLC) development and propose a novel therapeutic approach. Main methods: We investigated the cell viability, chemosensitivity, apoptosis, migration, and the cell cycle of A-549 and NCI-H1299 following treatment with cisplatin and CD73-small interfering RNA (siRNA) transfection. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to study the viability of studied groups and chemosensitivity of tumoral cells. Flow cytometry and 4',6-diamidino-2-phe-nylindole (DAPI) staining were used to investigate the apoptosis of NSCLC cells. Flow cytometry and the wound-healing assay were used to investigate the cell cycle and migration of NSCLC cells, respectively. The mRNA expression levels of c-Myc, caspase 3, ROCK, and MMP-9 were investigated to study the underlying molecular mechanism. Key findings: CD73-siRNA transfection has significantly decreased the cell viability and enhanced the chemosensitivity of A-549 and NCI-H1299 cells to cisplatin. CD73-siRNA has considerably stimulated apoptosis, arrested the cell cycle, inhibited tumor migration, downregulated the mRNA expression of c-Myc, MMP-9, and ROCK, and upregulated caspase 3 expression in NSCLC cells. Besides, combined cisplatin therapy with CD73-siRNA transfection has potentiated the aforementioned anti-tumoral effects of cisplatin on NSCLC cells. Significance: Besides suppressing anti-tumoral immune responses, tumor-intrinsic CD73 can facilitate NSCLC development, and the combined cisplatin therapy with CD73-siRNA transfection can substantially enhance the chemosensitivity of NSCLC to cisplatin and potentiates cisplatin-induced anti-tumoral effects on NSCLC.
      原文链接:
    • NSTL

    Protective mechanisms of telmisartan against hepatic ischemia/reperfusion injury in rats may involve PPARγ-induced TLR4/NF-κB suppression

    Mohamed A. MorsySeham A. Abdel-GaberRehab A. RifaaiMostafa M. Mohammed...
    1页
    查看更多>>摘要：Hepatic ischemia-reperfusion (I/R) is an important cause of liver damage in many clinical situations. Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) is an inflammatory pathway activated in hepatic I/R injury. Telmisartan, a selective angiotensin II type 1 receptor antagonist and peroxisome proliferator-activated receptor-gamma (PPARγ) partial agonist, can inhibit the expression of pro-inflammatory cytokines. The present work investigated the possible protective effect of telmisartan against hepatic I/R injury and explored its possible mechanisms in rats. Rats were divided into four equal groups: sham-operated control, telmisartan-treated sham-operated control, I/R untreated, and I/R telmisartan-treated groups. Hepatic injury was evaluated biochemically by serum activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and histopathological examination. Hepatic oxidative stress biomarkers, myeloperoxidase level, PPARγ and TLR4 mRNA expression, and NF-κB and active caspase 3 immunoexpression were determined. The study showed that telmisartan attenuated hepatic I/R, as evidenced by decreased serum ALT and AST activities and confirmed by improvement of the histopathological changes. The protective effect of telmisartan was associated with modulation of oxidative stress parameters, myeloperoxidase level, PPARγ and TLR4 mRNA expression, and NF-κB and caspase 3 immunoexpression. Taken together, the current study showed that telmisartan could protect the rat liver from I/ R injury. This hepatoprotective effect was attributed to, at least in part, increase in PPARγ expression and suppression of TLR4/NF-κB pathway.
      原文链接:
    • NSTL

    Drugs repurposed: An advanced step towards the treatment of breast cancer and associated challenges

    Jonaid Ahmad MalikSakeel AhmedBisma JanOnur Bender...
    1页
    查看更多>>摘要：Breast cancer (BC) is mostly observed in women and is responsible for huge mortality in women subjects globally. Due to the continued development of drug resistance and other contributing factors, the scientific community needs to look for new alternatives, and drug repurposing is one of the best opportunities. Here we light upon the drug repurposing with a major focus on breast cancer. BC is a division of cancer known as the leading cause of death of 2.3 million women globally, with 685,000 fatalities. This number is steadily rising, necessitating the development of a treatment that can extend survival time. All available treatments for BC are very costly as well as show side effects. This unfulfilled requirement of the anti-cancer drugs ignited an enthusiasm for drug repositioning, which means finding out the anti-cancer use of already marketed drugs for other complications. With the advancement in proteomics, genomics, and computational approaches, the drug repurposing process hastens. So many drugs are repurposed for the BC, including alkylating agents, antime-tabolite, anthracyclines, an aromatase inhibitor, mTOR, and many more. The drug resistance in breast cancer is rising, so reviewing how the challenges in breast cancer can be combated with drug repurposing. This paper provides the updated information on all the repurposed drugs candidates for breast cancer with the molecular mechanism responsible for their anti-tumor activity. Additionally, all the challenges that occur during the repurposing of the drugs are discussed.
      原文链接:
    • NSTL

    Novel doxorubicin / folate-targeted trans-ferulic acid-loaded PLGA nanoparticles combination: In-vivo superiority over standard chemotherapeutic regimen for breast cancer treatment

    Sahar A. HelmySaif El-MoftyAmal M. El GayarIbrahim M. El-Sherbiny...
    1页
    查看更多>>摘要：Aim: Doxorubicin/Cyclophosphamide (AC) is one of the standard adjuvant anthracycline-containing regimens that is still in use for breast cancer treatment. Cancer cell resistance and AC-induced side effects make treatment suboptimal and worsen patients' quality of life. This study aimed to improve trans-ferulic acid's (TFA) efficiency via loading into folate-receptor-targeted-poly lactic-co-glycolic acid nanoparticles (FA-PLGA-TFA NPs). Also, investigating both the antitumor efficacy of Doxorubicin (Dox)/FA-PLGA-TFA NPs combination against dimethyl benz [a] anthracene (DMBA)-induced breast cancer and its safety profile. Methods: FA-PLGA-TFA NPs were optimally fabricated and characterized. Levels of Notch1, Hes1, Wnt-3a, β-catenin, MMP-9, cyclin D1, Permeability-Glycoprotein (P-gp), ERα, PR, and HER2 were assessed as a measure of the antitumor efficacy of different treatment protocols. Histopathological examination of heart and bone, levels of ALT, AST, ALP, CK-MB, and WBCs count were evaluated to ensure the combination's safety profile. Key findings: Dox/FA-PLGA-TFA NPs not only inhibited Notch signaling but also suppressed Notch synergy with Wnt, estrogen, progesterone, and HER2 pathways. Interestingly, Dox/FA-PLGA-TFA NPs decreased P-gp level and preserved heart, bone, and liver health as well as WBCs count. Significance: Dox/FA-PLGA-TFA NPs reduced the side-effects of each single drug, and at the same time exerted excellent antitumor activity that surpass the AC regimen in evading cancer cell resistance and having a superior safety profile.
      原文链接:
    • NSTL