Amelioration of regulatory T cells by Lactobacillus delbrueckii and Lactobacillus rhamnosus in pristane-induced lupus mice model

Regulatory T cells (Tregs) play an indispensable role in the control of immune responses and induction of peripheral tolerance. Dysregulation of Tregs is involved in the pathogenesis of systemic lupus erythematosus (SLE). Tolerogenic probiotics have shown beneficial effects in the control of autoimmune diseases. We evaluated the prophylactic and therapeutic effects of Lactobacillus delbrueckii and Lactobacillus rhamnosus on Tregs and their related molecules in pristane-induced lupus mice model. Fifty-four female BALB/c mice (3–5 weeks) were randomly divided into nine groups. Lupus was induced in all groups using pristane. Prophylactic groups were treated from Day 0 (at the time of pristane injection) and treatment groups were treated 2 months later with L. rhamnosus, L. delbrueckii, mix of both probiotics, and prednisolone. One group was considered as SLE-induced control group without any treatment. Presence of antinuclear antibodies (ANA), antidouble-stranded DNA (anti-dsDNA), antiribonucleoprotein (anti-RNP), proteinuria, and serum level of creatinine, urea, the expression of forkhead box P3 (Foxp3), interleukin 6 (IL-6), IL-10, transforming growth factor β, and the number of Tregs were determined. SLE induction by pristane led to the formation of lipogranuloma, presence of ANA, anti-dsDNA, and anti-RNP. Probiotics consumption decreased the level of lipogranuloma, ANA, and anti-dsDNA. In addition, in probiotics receiving groups, Tregs and the expression level of Foxp3 increased, while IL-6 decreased. The effect of probiotics in the prophylactic group was more prominent. The results may indicate the effectiveness of L. delbrueckii and L. rhamnosus in the enhancement of Tregs and the decrease of inflammatory cytokines and disease severity in SLE-induced mice.     

Herbal medicine as an auspicious therapeutic approach for the eradication of Helicobacter pylori infection: A concise review

Helicobacter pylori (H. pylori) causes gastric mucosa inflammation and gastric cancer mostly via several virulence factors. Induction of proinflammatory pathways plays a crucial role in chronic inflammation, gastric carcinoma, and H. pylori pathogenesis. Herbal medicines (HMs) are nontoxic, inexpensive, and mostly anti-inflammatory reminding meticulous emphasis on the elimination of H. pylori and gastric cancer. Several HM has exerted paramount anti-H. pylori traits. In addition, they exert anti-inflammatory effects through several cellular circuits such as inhibition of 5′-adenosine monophosphate-activated protein kinase, nuclear factor-κB, and activator protein-1 pathway activation leading to the inhibition of proinflammatory cytokines (interleukin 1α [IL-1α], IL-1β, IL-6, IL-8, IL-12, interferon γ, and tumor necrosis factor-α) expression. Furthermore, they inhibit nitrous oxide release and COX-2 and iNOS activity. The apoptosis induction in Th1 and Th17-polarized lymphocytes and M2-macrophagic polarization and STAT6 activation has also been exhibited. Thus, their exact consumable amount has not been revealed, and clinical trials are needed to achieve optimal concentration and their pharmacokinetics. In the aspect of bioavailability, solubility, absorption, and metabolism of herbal compounds, nanocarriers such as poly lactideco-glycolide-based loading and related formulations are helpful. Noticeably, combined therapies accompanied by probiotics can also be examined for better clearance of gastric mucosa. In addition, downregulation of inflammatory microRNAs (miRNAs) by HMs and upregulation of those anti-inflammatory miRNAs is proposed to protect the gastric mucosa. Thus there is anticipation that in near future HM-based formulations and proper delivery systems are possibly applicable against gastric cancer or other ailments because of H. pylori.     

The role of nitric oxide signaling in renoprotective effects of hydrogen sulfide against chronic kidney disease in rats: Involvement of oxidative stress,autophagy and apoptosis

The interplay between H₂S and nitric oxide (NO) is thought to contribute to renal functions. The current study was designed to assess the role of NO in mediating the renoprotective effects of hydrogen sulfide in the 5/6 nephrectomy (5/6 Nx) animal model. Forty rats were randomly assigned to 5 experimental groups: (a) Sham; (b) 5/6 Nx; (c) 5/6Nx+sodium hydrosulfide-a donor of H ₂S, (5/6Nx+sodium hydrosulfide [NaHS]); (d) 5/6Nx+NaHS+ L -NAME (a nonspecific nitric oxide synthase [NOS] inhibitor); (e) 5/6Nx+NaHS+aminoguanidine (a selective inhibitor of inducible NOS [iNOS]). Twelve weeks after 5/6 Nx, we assessed the expressions of iNOS and endothelial NOS (eNOS), oxidative/antioxidant status, renal fibrosis, urine N-acetyl-b-glucosaminidase (NAG) activity as the markers of kidney injury and various markers of apoptosis, inflammation, remodeling, and autophagy. NaHS treatment protected the animals against chronic kidney injury as depicted by improved oxidative/antioxidant status, reduced apoptosis, and autophagy and attenuated messenger RNA (mRNA) expression of genes associated with inflammation, remodeling, and NAG activity. Eight weeks Nω-nitro-l-arginine methyl ester ( L -NAME) administration reduced the protective effects of hydrogen sulfide. In contrast, aminoguanidine augmented the beneficial effects of hydrogen sulfide. Our finding revealed some fascinating interactions between NO and H ₂S in the kidney. Moreover, the study suggests that NO, in an isoform-dependent manner, can exert renoprotective effects in 5/6 Nx model of CKD.     

A Novel Approach for Bioleaching of Sulfur,Iron, and Silica Impurities from Coal by Growing and Resting Cells of Rhodococcus spp

Coal is one of the most important sources of fossil energy on earth. However, direct combustion of coal with a high sulfur content can cause various environmental problems. Other constituents of coal that can cause environmental problems include iron oxide (hematite), iron hydroxide, and silica. In this study, growing and resting cells of Rhodococcus erythropolis strains PD1, R1, and FMF, and R. qingshengii were used in heterotrophic removal of sulfur and bioleaching of iron and silica from coal. All of the mentioned strains have an ability of dibenzothiophene (DBT) desulfurization via 4-S pathway. 2-hydroxybiphenyl, sulfate, and ferric ions (Fe³⁺) were assayed by Gibb’s test, barium chloride (BaCl₂), and thiocyanate ions (SCN^?), respectively. FTIR and XRF analyzer were used for detection of the coal bioleaching process by the selected strain of R. erythropolis (PD1). Results indicated that all strains have the ability to grow on coal as the sulfur source. Among them, strain PD1 produced the highest optical density and continued to grow even after 150-h incubation. In both growing- and resting-cells experiments, strain PD1 desulfurized coal most readily compared to other strains. Results of XRF showed that growing cells of strain PD1 had high desulfurizing ability of coal (46%) compared to resting cells in the absence of any carbon sources (24%). Growing cells of strain PD1 also leached 46% of the iron and 14% of the silicate after 7?days of incubation. Resting cells of PD1 leached 32% of the iron as determined by XRF analysis. Also, growing cells of PD1 removed most SiO₂ from coal as detected and confirmed by FTIR and XRF. To the best of our knowledge, this is the first report on bioleaching of iron and silica from coal by R. erythropolis strain PD1, making it a suitable candidate for coal bioremediation.     

Association of TNF-308 G>A polymorphism located in tumor necrosis factor a with the risk of developing cervical cancer and results of pap smear

Tumor necrosis factor a (TNFa) is an inflammatory cytokine that plays a crucial role in the immune response and the progression of cervical lesions. There is a growing body of data evaluating the value of a genetic variant in the TNFa gene with the risk of developing cervical cancer. The aim of this study was to explore the association of a variant, TNF-308 G>A, residing in the TNFa gene with cervical cancer. A total of 91 women with cervical cancer and 161 women as the control group were recruited. DNA was extracted, and Taqman®-probes-based assay was used for genotyping. Our results showed that the minor allele frequency was 0.3 in total population, and the frequency of minor allele A was more in the case group compared with the control. The regression models in different genetic models also revealed that the allele A is a potential risk factor for the development of cervical cancer. In particular, in the dominant model, patients with AG and AA genotypes had a higher risk of developing cervical cancer with odds ratio (OR) of 2.75 (95% confidence interval [CI]: 1.57-4.83, <0.001) and OR of 7.27 (95%CI: 2.5-20.8, <0.001), compared with the GG genotype. Moreover, a similar outcome was obtained for smear test results. Our study demonstrated that TNF-308 G>A located on TNF-a was associated with the risk of cervical cancer, supporting further studies in a larger population and multicenter setting to show the value of emerging markers as risk stratification biomarkers in cervical cancer.     

Selenium as an adjuvant for modification of radiation response

Ionizing radiation plays a central role in several medical and industrial purposes. In spite of the beneficial effects of ionizing radiation, there are some concerns related to accidental exposure that could pose a threat to the lives of exposed people. This issue is also very critical for triage of injured people in a possible terror event or nuclear disaster. The most common side effects of ionizing radiation are experienced in cancer patients who had undergone radiotherapy. For complete eradication of tumors, there is a need for high doses of ionizing radiation. However, these high doses lead to severe toxicities in adjacent organs. Management of normal tissue toxicity may be achieved via modulation of radiation responses in both normal and malignant cells. It has been suggested that treatment of patients with some adjuvant agents may be useful for amelioration of radiation toxicity or sensitization of tumor cells. However, there are always some concerns for possible severe toxicities and protection of tumor cells, which in turn affect radiotherapy outcomes. Selenium is a trace element in the body that has shown potent antioxidant and radioprotective effects for many years. Selenium can potently stimulate antioxidant defense of cells, especially via upregulation of glutathione (GSH) level and glutathione peroxidase activity. Some studies in recent years have shown that selenium is able to mitigate radiation toxicity when administered after exposure. These studies suggest that selenium may be a useful radiomitigator for an accidental radiation event. Molecular and cellular studies have revealed that selenium protects different normal cells against radiation, while it may sensitize tumor cells. These differential effects of selenium have also been revealed in some clinical studies. In the present study, we aimed to review the radiomitigative and radioprotective effects of selenium on normal cells/tissues, as well as its radiosensitive effect on cancer cells.     

Telmisartan anti‐cancer activities mechanism through targeting N‐cadherin by mimicking ADH‐1 function

This study aimed to investigate if Telmisartan as a novel N‐cadherin antagonist, can overcome cell migration of cancer cells. We investigated the mechanism and influence of Docetaxel and Telmisartan (as an analogous to ADH‐1, which is a well‐known N‐cadherin antagonist) on cancer cells. The effect of ADH‐1 and Telmisartan on cell attachment in PC3, DU145, MDA‐MB‐468 cell lines using recombinant human N‐cadherin was studied. Cell viability assay was performed to examine the anti‐proliferative effects of Telmisartan, ADH‐1 and Docetaxel. Migration was examined via wound healing assay, and apoptosis was determined by flow cytometry. The expression of AKT‐1 as a downstream gene of N‐cadherin signalling pathway was assayed by real‐time PCR. Treatment of PC3, MDA‐MB‐468 and DU145 cells with Telmisartan (0.1 µM) and ADH‐1 (40 µM) resulted in 50%, 58% and approximately 20% reduction in cell attachment to N‐cadherin coated plate respectively. It shows reduction of cell attachment in PC3 and MDA‐MB‐468 cell lines appeared to be more sensitive than that of DU145 cells to the Telmisartan and ADH‐1 treatments. Telmisartan (0.1 µM) and Docetaxel (0.01 nM) significantly reduced cell migration in PC3 and MDA‐MB‐468 cell lines compared with the control group. Using Real‐time PCR, we found that Telmisartan, Docetaxel and ADH‐1 had significant influence on the AKT‐1 mRNA level. The results of the current study for the first time suggest that, Telmisartan, exerts anti‐proliferation and anti‐migration effects by targeting antagonistically N‐cadherin. Also, these data suggest that Telmisartan as a less expensive alternative to ADH‐1 could potentiate Docetaxel anticancer effects.     

Multi-stage structure-based virtual screening approach towards identification of potential SARS-CoV-2 NSP13 helicase inhibitors

On account of its crucial role in the virus life cycle, SARS-COV-2 NSP13 helicase enzyme was exploited as a promising target to identify a novel potential inhibitor using multi-stage structure-based drug discovery approaches. Firstly, a 3D pharmacophore was generated based on the collected data from a protein-ligand interaction fingerprint (PLIF) study using key interactions between co-crystallised fragments and the NSP13 helicase active site. The ZINC database was screened through the generated 3D-pharmacophore retrieving 13 potential hits. All the retrieved hits exceeded the benchmark score of the co-crystallised fragments at the molecular docking step and the best five-hit compounds were selected for further analysis. Finally, a combination between molecular dynamics simulations and MM-PBSA based binding free energy calculations was conducted on the best hit (compound FWM-1) bound to NSP13 helicase enzyme, which identified FWM-1 as a potential potent NSP13 helicase inhibitor with binding free energy equals −328.6 ± 9.2 kcal/mol.