Vinpocetine and Lactobacillus improve fatty liver in rats: role of adiponectin and gut microbiome.

Therapeutics that interfere with the damage/pathogen-associated molecular patterns (DAMPs/PAMPs) have evolved as promising candidates for hepatic inflammation like that occurring in non-alcoholic fatty liver disease (NAFLD). In the current study, we examined the therapeutic impact of the phosphodiesterase-1 inhibitor vinpocetine (Vinpo), alone or when combined with Lactobacillus, on hepatic abnormalities caused by a 13-week high-fat diet (HFD) and diabetes in rats. The results show that Vinpo (10 and 20 mg/kg/day) dose-dependently curbed HFD-induced elevation of liver injury parameters in serum (ALT, AST) and tissue histopathology. These effects were concordant with Vinpo's potential to ameliorate HFD-induced fibrosis (Histological fibrosis score, hydroxyproline, TGF-ß1) and oxidative stress (MDA, NOx) alongside restoring the antioxidant-related parameters (GSH, SOD, Nrf-2, HO-1) in the liver. Mechanistically, Vinpo attenuated the hepatocellular release of DAMPs like high mobility group box (HMGB)1 alongside lowering the overactivation of the pattern recognition receptors including, toll-like receptor (TLR)4 and receptor for advanced glycation end-products (RAGE). Consequently, there was less activation of the transcription factor nuclear factor-kappa B that lowered production of the proinflammatory cytokines TNF-α and IL-6 in Vinpo-treated HFD/diabetes rats. Compared to Vinpo treatment alone, Lactobacillus probiotics as adjunctive therapy with Vinpo significantly improved the disease-associated inflammation and oxidative stress injury, as well as the insulin resistance and lipid profile abnormalities via enhancing the restoration of the symbiotic microbiota. In conclusion, combining Vinpo and Lactobacillus probiotics may be a successful approach for limiting NAFLD in humans.

Emerging insights into macrophage extracellular traps in bacterial infections.

Macrophages possess a diverse range of well-defined capabilities and roles as phagocytes, encompassing the regulation of inflammation, facilitation of wound healing, maintenance of tissue homeostasis, and serving as a crucial element in the innate immune response against microbial pathogens. The emergence of extracellular traps is a novel strategy of defense that has been observed in several types of innate immune cells. In response to infection, macrophages are stimulated and produce macrophage extracellular traps (METs), which take the form of net-like structures, filled with strands of DNA and adorned with histones and other cellular proteins. METs not only capture and eliminate microorganisms but also play a role in the development of certain diseases such as inflammation and autoimmune disorders. The primary objective of this study is to examine the latest advancements in METs for tackling bacterial infections. We also delve into the current knowledge and tactics utilized by bacteria to elude or endure the effects of METs. Through this investigation, we hope to shed light on the intricate interactions between bacteria and the host's immune system, particularly in the context of microbicidal effector mechanisms of METs. The continued exploration of METs and their impact on host defense against various pathogens opens up new avenues for understanding and potentially manipulating the immune system's response to infections.

Neutrophil extracellular traps in bacterial infections and evasion strategies.

Neutrophils are innate immune cells that have a vital role in host defense systems. Neutrophil extracellular traps (NETs) are one of neutrophils' defense mechanisms against pathogens. NETs comprise an ejected lattice of chromatin associated with histones, granular proteins, and cytosolic proteins. They are thought to be an efficient strategy to capture and/or kill bacteria and received intensive research interest in the recent years. However, soon after NETs were identified, it was observed that certain bacteria were able to evade NET entrapment through many different mechanisms. Here, we outline the recent progress of NETs in bacterial infections and the strategies employed by bacteria to evade or withstand NETs. Identifying the molecules and mechanisms that modulate NET release will improve our understanding of the functions of NETs in infections and provide new avenues for the prevention and treatment of bacterial diseases.

The Dual Roles of Activating Transcription Factor 3 (ATF3) in Inflammation, Apoptosis, Ferroptosis, and Pathogen Infection Responses.

Transcription factors are pivotal regulators in the cellular life process. Activating transcription factor 3 (ATF3), a member of the ATF/CREB (cAMP response element-binding protein) family, plays a crucial role as cells respond to various stresses and damage. As a transcription factor, ATF3 significantly influences signal transduction regulation, orchestrating a variety of signaling pathways, including apoptosis, ferroptosis, and cellular differentiation. In addition, ATF3 serves as an essential link between inflammation, oxidative stress, and immune responses. This review summarizes the recent advances in research on ATF3 activation and its role in regulating inflammatory responses, cell apoptosis, and ferroptosis while exploring the dual functions of ATF3 in these processes. Additionally, this article discusses the role of ATF3 in diseases related to pathogenic microbial infections. Our review may be helpful to better understand the role of ATF3 in cellular responses and disease progression, thus promoting advancements in clinical treatments for inflammation and oxidative stress-related diseases.

LppA is a novel plasminogen receptor of Mycoplasma bovis that contributes to adhesion by binding the host extracellular matrix and Annexin A2.

Mycoplasma bovis is responsible for various inflammatory diseases in cattle. The prevention and control of M. bovis are complicated by the absence of effective vaccines and the emergence of multidrug-resistant strains, resulting in substantial economic losses worldwide in the cattle industry. Lipoproteins, vital components of the Mycoplasmas cell membrane, are deemed potent antigens for eliciting immune responses in the host upon infection. However, the functions of lipoproteins in M. bovis remain underexplored due to their low sequence similarity with those of other bacteria and the scarcity of genetic manipulation tools for M. bovis. In this study, the lipoprotein LppA was identified in all examined M. bovis strains. Utilizing immunoelectron microscopy and Western blotting, it was observed that LppA localizes to the surface membrane. Recombinant LppA demonstrated dose-dependent adherence to the membrane of embryonic bovine lung (EBL) cells, and this adhesion was inhibited by anti-LppA serum. In vitro binding assays confirmed LppA's ability to associate with fibronectin, collagen IV, laminin, vitronectin, plasminogen, and tPA, thereby facilitating the conversion of plasminogen to plasmin. Moreover, LppA was found to bind and enhance the accumulation of Annexin A2 (ANXA2) on the cell membrane. Disrupting LppA in M. bovis significantly diminished the bacterium's capacity to adhere to EBL cells, underscoring LppA's function as a bacterial adhesin. In conclusion, LppA emerges as a novel adhesion protein that interacts with multiple host extracellular matrix proteins and ANXA2, playing a crucial role in M. bovis's adherence to host cells and dissemination. These insights substantially deepen our comprehension of the molecular pathogenesis of M. bovis.

New Pyrazole-Clubbed Pyrimidine or Pyrazoline Hybrids as Anti-Methicillin-Resistant Staphylococcus aureus Agents: Design, Synthesis, In Vitro and In Vivo Evaluation, and Molecular Modeling Simulation.

Two hybrid series of pyrazole-clubbed pyrimidines 5a-c and pyrazole-clubbed pyrazoline compounds 6a,b and 7 were designed as attractive scaffolds to be investigated in vitro and in vivo for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. From the results of the in vitro antibacterial screening, compound 5c showed excellent activity (minimal inhibitory concentration, MIC = 521 µM) when compared with that of the reference antibiotic levofloxacin (MIC = 346 µM). The inhibition of the target dihydrofolate reductase (DHFR) enzyme by compounds 4 and 5a-c (IC50 = 5.00 ± 0.23, 4.20 ± 0.20, 4.10 ± 0.19, and 4.00 ± 0.18 µM, respectively) was found to be better than the reference drug trimethoprim (IC50 = 5.54 ± 0.28 µM). Molecular modeling simulation results have justified the order of activity of all the newly synthesized compounds as DHFR enzyme inhibitors, and compound 5c exhibited the best binding profile (-13.6169386 kcal/mol). Hence, the most potent inhibitor of the DHFR enzyme, 5c, was chosen to be evaluated in vivo for its activity in treating MRSA-induced keratitis in rats and that, in turn, significantly (P < 0.0001) reduced infection in rats when compared to MRSA-treated group results.

Molecular characterization of enterotoxin genes in methicillin-resistant S. aureus isolated from food poisoning outbreaks in Egypt.

BACKGROUND: Staphylococcus aureus (S. aureus), especially methicillin-resistant S. aureus (MRSA), is a known disease-causing bacteria with many associated health hazards. Staphylococcal food poisoning can result from staphylococcal enterotoxins (SEs). METHODS: In this study, 50 S. aureus isolates were isolated from the gastrointestinal tract (GIT) clinical samples of patients with food poisoning in clinical laboratories at Mansoura University Hospital, Egypt. For determination their antibiogram, these isolates were tested for antimicrobial sensitivity against 12 antimicrobial agents using the agar disk diffusion test. After DNA extraction from the isolates, conventional polymerase chain reaction (PCR) was used to detect mecA and SEs genes. RESULTS: As a result, all isolates were ampicillin and cefoxitin-resistant, while 86% (43 of 50) of the tested isolates exhibited multidrug resistance (MDR). In contrast, the highest sensitivity was confirmed against vancomycin, linezolid and quinolones, namely ciprofloxacin and norfloxacin. Although 100% of the isolates were mecA positive, staphylococcal enterotoxin genes set-A, set-B, set-C, set-G, set-M, and set-O genes were detected in 56%, 20%, 8%, 32%, 16%, and 24%, of the tested isolates, respectively. Finally, isolates encompassing SEs genes were used to validate a microarray chip, indicating its potential for a better methodological approach for detecting and identifying SEs in human samples. CONCLUSION: The genotypic findings of this study may help explain the enterotoxigenic patterns in S. aureus among Egyptian patients with food poisoning.

WITHDRAWN: Vinpocetine and Lactobacillus improve fatty liver in rats via modulating the oxidative stress, inflammation, adiponectin and gut microbiome.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

Valuable effects of lactobacillus and citicoline on steatohepatitis: role of Nrf2/HO-1 and gut microbiota.

Non-alcoholic steatohepatitis (NASH) is a more dangerous form of chronic non-alcoholic fatty liver disease (NAFLD). In the current investigation, the influence of citicoline on high-fat diet (HFD)-induced NASH was examined, both alone and in combination with Lactobacillus (probiotic). NASH was induced by feeding HFD (10% sugar, 10% lard stearin, 2% cholesterol, and 0.5% cholic acid) to rats for 13 weeks and received single i.p. injection of streptozotocin (STZ, 30 mg/kg) after 4 weeks. Citicoline was given at two dose levels (250 mg and 500 mg, i.p.) at the beginning of the sixth week, and in combination with an oral suspension of Lactobacillus every day for eight weeks until the study's conclusion. HFD/STZ induced steatohepatitis as shown by histopathological changes, elevated serum liver enzymes, serum hyperlipidemia and hepatic fat accumulation. Moreover, HFD convinced oxidative stress by increased lipid peroxidation marker (MDA) and decreased antioxidant enzymes (GSH and TAC). Upregulation of TLR4/NF-kB and the downstream inflammatory cascade (TNF-α, and IL-6) as well as Pentaraxin, fetuin-B and apoptotic markers (caspase-3 and Bax) were observed. NASH rats also had massive increase in Bacteroides spp., Fusobacterium spp., E. coli, Clostridium spp., Providencia spp., Prevotella interrmedia, and P. gingivalis while remarkable drop in Bifidobacteria spp. and Lactobacillus spp. Co-treatment with citicoline alone and with Lactobacillus improve histopathological NASH outcomes and reversed all of these molecular pathological alterations linked to NASH via upregulating the expression of Nrf2/HO-1 and downregulating TLR4/NF-kB signaling pathways. These results suggest that citicoline and lactobacillus may represent new hepatoprotective strategies against NASH progression.

The linkage between prevalence of integron I and reduced susceptibility to biocides in MDR Klebsiella pneumoniae isolated from neonates.

Background and Objectives: Klebsiella pneumoniae causes challenging nosocomial fatal infections including neonatal sepsis. Our study aims at clarifying the contribution of integrons in the observed reduced susceptibility of multidrug-resistant (MDR) K. pneumoniae isolated from septicemic neonates to the clinically used antimicrobial agents and biocides. Materials and Methods: Eighty-six K. pneumoniae isolates were collected from Mansoura University Children's Hospital from septicemic neonates. Isolates were subjected to antibiotic and biocide susceptibility using disk diffusion and the agar dilution method, respectively. The distribution of different classes of integrons was screened in the isolates by PCR. Detected inegron I was sequenced in selected isolates. Results: Fifty-seven isolates (66.27%) were MDR. In the MDR isolates, class I integron was detected in 23 (40.3%), integron III was detected in 20 (35%), whereas integron II could not be detected. Sequencing results of integron I from MDR K. pneumoniae isolates revealed that only aminoglycoside and folate synthesis inhibitors gene cassettes were detected, while the rest of the resistance genes were not associated with integron I. Conclusion: The presence of integron I in MDR K. pneumoniae tested isolates may contribute only to some biocide resistance, however, it does not seem to be the only contributor in multiple drug resistance.

A novel therapeutic combination of dapagliflozin, Lactobacillus and crocin attenuates diabetic cardiomyopathy in rats: Role of oxidative stress, gut microbiota, and PPARγ activation.

AIMS: Diabetic cardiomyopathy is diagnosed by the development of abnormality in the structure and performance of myocardium in diabetic mellitus (DM) patients. Recent studies reported the association between altered gut microbiota and metabolic disorders like diabetes and cardiovascular diseases. Here, we aimed to investigate the gut-heart axis in an experimental animal model where we developed a novel therapeutic combination of dapagliflozin, crocin prebiotic and Lactobacilli probiotic to correct induced diabetic cardiomyopathy. MATERIALS AND METHODS: Diabetes mellitus was induced by Intraperitoneal (i.p) streptozotocin in male rats. The experimental design includes the administration of the tested drugs (Crocin, Dapagliflozin) solely and with Lactobacillus, or in combination therapy with and without Lactobacillus to the diabetic rats for six weeks. Clinical and microscopic evaluation scoring for cardiac tissues were determined. Biochemical markers including blood glucose level, adiponectin, resistin, cardiac injury markers, lipid profile, antioxidant enzymes, pro and anti-inflammatory markers were assessed. In addition, quantitative relative expression of PPARγ and TXINP genes and capsase-3 levels were measured. The change in the microbiota abundance was investigated using real-time PCR. KEY FINDINGS: This study demonstrated the synergistic effect of the triple combination; dapagliflozin, crocin prebiotic, and Lactobacillus fermentum and Lactobacillus delbrueckii probiotic in treating diabetic cardiomyopathy in rats. The triple combination significantly reduced the oxidative, inflammatory, apoptotic activities induced by streptozotocin STZ and helped in restoring the symbiotic gut microbiota. SIGNIFICANCE: It is worthy to perform this study in clinical trials as a primary step to include crocin and Lactobacilli in the therapeutic protocols of diabetic cardiomyopathy.

Early forecasting of COVID-19 case progression with hematological and biochemical parameters of patients in Egypt.

The coronavirus pandemic 2019 (COVID-19) is changing the world and reshape all aspects of life. Side by side to global efforts to develop potential vaccines and effective drugs against COVID-19, clinical parameters scanning the prognosis of COVID-19 infection are badly required to help the clinicians in premature management of COVID-19 cases before critical progression. The main objective of our study is to specify reliable biomarkers which differentially change upon case progression and clearly reflect the extent of lung lesions. Forty-one patients from Mansoura area, confirmed for COVID-19 infection were classified according to the diameter of lung lesions measured by lung computed tomography (CT) into mild and severe cases including 66% and 34% of all patients, respectively. COVID-19 patients were followed since hospital admission for comparative studies covering measured biochemical and hematological parameters. Based on the degree of severity, five different biomarkers mainly; D-dimer, lactate dehydrogenase (LDH), C-reactive protein (CRP), lymphocytes and ferritin were found to clearly oscillate in response to COVID-19 infection and upon case transition from mild to severe. In our study, significantly higher levels of almost all the biomarkers except lymphocyte count, were detected in patients having severe complications of COVID-19 infection in contrast with non-severe patients.

Repurposing pantoprazole and haloperidol as efflux pump inhibitors in azole resistant clinical Candida albicans and non-albicans isolates.

Candida species have a major role in nosocomial infections leading to high morbidity and mortality. Increased resistance to various antifungals, especially azoles is a significant problem. One of the main mechanisms for azole resistance is the up-regulation of efflux pump genes including CDR1 and MDR1. In the current study, clinical Candida isolates were identified to the species level and the antifungal susceptibility (AFS) of different Candida species was determined by disk diffusion method. Furthermore, the main mechanisms of azole resistance were investigated. Finally, haloperidol and pantoprazole were tested for their potential synergistic effect against fluconazole-resistant isolates. One hundred and twenty-two Candida clinical isolates were used in this study. 70 isolates were Candida albicans (57.4%), the non-albicans Candida species include: C. krusei (20.5%), C. tropicalis (6.6%), C. parapsilosis (5.7%), C. dubliniensis (4.9%) and C. glabrata (4.9%). The AFS testing showed that resistance to fluconazole and voriconazole were 13.1% (n = 16) and 9.8% (n = 12), respectively. Among the 16 resistant isolates, eight isolates (50%) were strong biofilm producers, seven (43.8 %) formed intermediate biofilm and one had no biofilm. All resistant strains overexpressed efflux pumps. Using RT-PCR, the efflux genes CDR1, MDR1 and ABC2 were over-expressed in azole resistant isolates. Haloperidol-fluconazole and pantoprazole-fluconazole combinations reduced the MIC of fluconazole in resistant isolates. The current study showed an increase in azole resistance of Candida species. The majority of resistant isolates form biofilm, and overexpress efflux pumps. Pantoprazole and Haloperidol showed a noteworthy effect as efflux pump inhibitors which oppose the fluconazole resistance in different Candida species.

Combating Bacterial Biofilm Formation in Urinary Catheter by Green Silver Nanoparticle.

Urinary catheters are commonly associated with urinary tract infections. This study aims to inhibit bacterial colonisation and biofilm of urinary tract catheters. Silicon catheter pieces were varnished with green silver nanoparticles (AgNPs) using Pistacia lentiscus mastic to prevent bacterial colonisation. Pomegranate rind extract was used to synthesize AgNPs. AgNPs were characterized by UV-Vis spectroscopy, X-ray crystallography, and transmission electron microscopy (TEM). Results obtained revealed that the size of most AgNPs ranged between 15-25 nm and they took crystallised metal and oxidised forms. The amounts of released silver ions from 1 cm pieces of catheters coated with AgNPs were estimated for five days and ranged between 10.82 and 4.8 µg. AgNPs coated catheters significantly inhibited the colonisation of catheters by antibiotic-resistant clinical Gram-positive (Staphylococcus epidermidis and Staphylococcus aureus) and Gram-negative (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa) bacteria. AgNPs-varnish was more active against Gram-negative bacteria than Gram-positive bacteria. The significant inhibitory effect of coated catheters lasted for 72 h for both Gram-positive and Gram-negative bacteria. Varnishing catheters with AgNPs may help to prevent bacterial colonisation and infections.

In silico screening of potent inhibitors against COVID-19 key targets from a library of FDA-approved drugs.

Coronavirus disease (COVID-19) is an emerging pandemic that threatens the world since the early days of 2020. Development of vaccines or new drugs against COVID-19 comprises several stages of investigation including efficacy, safety, and approval studies. A shortcut to this delicate pathway is computational-based analysis of FDA-approved drugs against assigned molecular targets of the coronavirus. In this study, we virtually screened a library of FDA-approved drugs prescribed for different therapeutic purposes against versatile COVID-19 specific proteins which are crucial for the virus life cycle. Three antibiotics in our screening polymyxin B, bafilomycin A, and rifampicin show motivating binding stability with more than one target of the virus. Another category of tested drugs is oral antiseptics of mouth rinsing solutions that unexpectedly exhibited significant affinity to the target proteins employed by the virus for attachment and cell internalization. Other OTC drugs widely used and tested in our study are heartburn drugs and they show no significant binding. We tested also some other drugs falling under the scope of investigation regarding interference with a degree of severity of COVID-19 like angiotensin II blockers used as antihypertensive, and our study suggests a therapeutic rather than predisposing effect of these drugs against COVID-19.

Prognostic value of baseline carotid blood flow in critically ill children with septic shock.

BACKGROUND AND AIM: Hemodynamic monitoring and cardiac output (CO) assessment in the ICU have been trending toward less invasive methods. Carotid blood flow (CBF) was suggested as a candidate for CO assessment. The present study aimed to test the value of carotid artery ultrasound analysis in prediction of mortality in pediatric patients with septic shock. METHODOLOGY/PRINCIPAL FINDING: Forty children with septic shock were included in the study. Upon admission, patients were subjected to careful history taking and thorough clinical examination. The consciousness level was assessed by the Glasgow Coma Scale (GCS). Laboratory assessment included complete blood count, C-reactive protein, arterial blood gases, serum electrolytes, and liver and kidney function tests. Electrical cardiometry was used to evaluate hemodynamic parameters. Patients were also subjected to transthoracic 2-D echocardiography. CBF was evaluated using GE Vivid S5 ultrasound device through dedicated software. At the end of study, 14 patients (35.0%) died. It was found that survivors had significantly higher CBF when compared non-survivors [median (IQR): 166.0 (150.0-187.3) versus 141.0 (112.8-174.3), p = 0.033]. In addition, it was noted that survivors had longer ICU stay when compared with non-survivors [16.5 (9.8-31.5) versus 6.5 (3.0-19.5) days, p = 0.005]. ROC curve analysis showed that CBF could significantly distinguish survivors from non-survivors [AUC (95% CI): 0.3 (0.11-0.48), p = 0.035] (Fig 2). Univariate logistic regression analysis identified type of shock [OR (95% CI): 28.1 (4.9-162.4), p<0.001], CI [OR (95% CI): 0.6 (0.43-0.84), p = 0.003] and CBF [OR (95% CI): 0.98 (0.96-0.99), p = 0.031]. However, in multivariate analysis, only type of shock significantly predicted mortality. CONCLUSIONS: CBF assessment may be a useful prognostic marker in children with septic shock.

Soil-Associated Bacillus Species: A Reservoir of Bioactive Compounds with Potential Therapeutic Activity against Human Pathogens.

Soil hosts myriads of living organisms with the extensive potential to produce bioactive compounds. Bacteria are the major soil inhabitants that represent a rich reservoir for antibiotic production along with their role in recycling nutrients and maintenance of the soil ecosystem. Here, from 55 tested soil samples, we isolated and identified a novel antibiotic-producing bacterial strain with a phylogenetically closest match to Bacillus subtilis sp. based on BLASTN search of GenBank for the 16S rRNA gene sequence. We characterized this novel strain through microscopic, biochemical, and molecular techniques, combined with testing its potential antimicrobial activity. Chemical studies revealed that the antibiotic produced by this strain is a glycopeptide. It exhibited profound activity against both methicillin-resistant Staphylococcus aureus (MRSA) and Candida albicans. The antibiotic is optimally produced at 37 °C after 28 h of growth. The biocompatibility of the extracted antibiotic was tested over a wide range of factors including temperature, pH, surfactants, and metal salts. To confirm its therapeutic potential, a sterile solution of the antibiotic was tested in vivo against bacteria-induced keratitis in rats where significant healing activity was recorded. Hence, this soil Bacillus strain may lead to the development of novel antibiotics for the treatment of human pathogens.

The therapeutic role of lactobacillus and montelukast in combination with metformin in diabetes mellitus complications through modulation of gut microbiota and suppression of oxidative stress.

Male reproductive dysfunction is one of the overlooked findings of diabetes mellitus (DM) that deserves greater scientific attention. This study is designed to explore the therapeutic potential of metformin and montelukast, in combination with Lactobacillus, for modulation of intestinal flora and suppression of oxidative stress in testicular and liver damage in diabetic male rats. A DM model was induced by streptozotocin (STZ)which caused functional, biochemical, and inflammatory injuries to the testicular and liver tissues. The experimental panel included nine rat groups: normal control, normal control plus metformin, normal control plus montelukast, DM control, DM plus montelukast, DM plus a combination of metformin and Lactobacillus, DM plus a combination of montelukast and Lactobacillus, and DM plus a combination of metformin and montelukast. In parallel, clinical evaluation of microscopic examination scoring, and hepatic and testicular injuries, were evaluated. Biochemical markers including glucose level, lipid profile, inflammatory markers (tumor necrosis factor- (TNF-α) and interleukin-17 (IL-17), Caspase-3, and Bax proteins expressions were measured. The change in the microbiota abundance was investigated using conventional and real-time PCR. The current study revealed a significant difference in the relative abundance of microbiota, where DM is associated with an enormous increase of Bacteroides spp., Clostridium spp., E. coli, and Fusobacterium spp., and a significant decrease in Bifidobacteria spp., and Lactobacillus spp., in contrast with normal control. Metformin and montelukast, in combination with Lactobacillus, significantly reversed the testicular and liver damage caused by STZ. Moreover, the drugs significantly reduced the oxidative, inflammatory, and apoptotic activities induced by STZ.

The Link between Occurrence of Class I Integron and Acquired Aminoglycoside Resistance in Clinical MRSA Isolates.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of nosocomial infections because of its high resistance. Here, we study the antibiotic resistance in MRSA clinical isolates and their relation to integron I occurrence. A total of 88 clinical Staphylococcusaureus isolates were collected. MRSA were identified by the disk diffusion method (DDM) and confirmed by PCR, and antibiogram was determined by DDM. Integron I, II and the aacA4 gene were investigated by PCR. Integrase-positive strains were analyzed for the presence of resistance gene cassettes by sequencing. All isolates were identified as MRSA by DDM and confirmed by PCR. All isolates were resistant to ampicillin and cefoxitin. Concerning aminoglycosides, the frequency of resistance was reported for streptomycin (60.7%), tobramycin (37.1%) gentamicin (36%), and for amikacin (15.9%). Integron I was detected in 41 isolates (46.6%), while integron II was detected in three isolates (3.4%). Sequencing of the integron I-cassette indicated the exclusive prevalence of addA gene variants mediating aminoglycoside resistance. The aacA4 gene was found in DNA of 31 isolates (35.22%). This study revealed the high existence of MRSA. Furthermore, the AacA4 gene and class I integron harboring aadA gene were predominant in MRSA isolates.

A Novel Combination Therapy Using Rosuvastatin and Lactobacillus Combats Dextran Sodium Sulfate-Induced Colitis in High-Fat Diet-Fed Rats by Targeting the TXNIP/NLRP3 Interaction and Influencing Gut Microbiome Composition.

Inflammasome targeting and controlling dysbiosis are promising therapeutic approaches to control ulcerative colitis. This report is the first to investigate the mechanisms underlying the coloprotective effects of rosuvastatin and Lactobacillus and their combined therapy on dextran sodium sulfate (DSS)-induced colitis in high-fat diet (HFD)-fed rats. Our results demonstrate the aggravation of intestinal inflammation as a consequence of an HFD following DSS administration. An association between dyslipidemia, LDL oxidation, CD36 expression, ROS generation, thioredoxin-interacting protein (TXNIP) upregulation, and NLRP3 inflammasome activation was demonstrated by DSS exposure in HFD-fed rats. We demonstrated that rosuvastatin/Lactobacillus significantly suppressed the DSS/HFD-induced increase in colon weight/length ratio, DAI, MDI, and myeloperoxidase, as well as corrected dysbiosis and improved histological characteristics. Additionally, caspase-1 activity and IL-1ß-driven pyroptotic activity was significantly reduced. Rosuvastatin/Lactobacillus showed prominent anti-inflammatory effects as revealed by the IL-10/IL-12 ratio and the levels of TNF-α and IL-6. These latter effects may be attributed to the inhibition of phosphorylation-induced activation of NF-κB and a concomitant reduction in the expression of NLRP3, pro-IL-1ß, and pro-IL-18. Furthermore, rosuvastatin/Lactobacillus reduced Ox-LDL-induced TXNIP and attenuated the inflammatory response by inhibiting NLRP3 inflammasome assembly. To conclude, rosuvastatin/Lactobacillus offers a safe and effective strategy for the management of ulcerative colitis.