Antimicrobial resistance (AMR) is a ubiquitous public health menace. AMR emergence causes complications in treating infections contributing to an upsurge in the mortality rate. The epidemic of AMR in sync with a high utilization rate of antimicrobial drugs signifies an alarming situation for the fleet recovery of both animals and humans. The emergence of resistant species calls for new treatments and therapeutics. Current records propose that health drug dependency, veterinary medicine, agricultural application, and vaccination reluctance are the primary etymology of AMR gene emergence and spread. Recently, several encouraging avenues have been presented to contest resistance, such as antivirulent therapy, passive immunization, antimicrobial peptides, vaccines, phage therapy, and botanical and liposomal nanoparticles. Most of these therapies are used as cutting‐edge methodologies to downplay antibacterial drugs to subdue the resistance pressure, which is a featured motive of discussion in this review article. AMR can fade away through the potential use of current cutting‐edge therapeutics, advancement in antimicrobial susceptibility testing, new diagnostic testing, prompt clinical response, and probing of new pharmacodynamic properties of antimicrobials. It also needs to promote future research on contemporary methods to maintain host homeostasis after infections caused by AMR. Referable to the microbial ability to break resistance, there is a great ultimatum for using not only appropriate and advanced antimicrobial drugs but also other neoteric diverse cutting‐edge therapeutics.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a pathological accumulation of hepatic lipid closely linked with many metabolic disorders, oxidative stress and inflammation. We aimed to evaluate the hepatoprotective effect of bee bread on oxidative stress and inflammatory parameters in MAFLD rats. Twenty-eight male Sprague-Dawley rats were assigned into four groups (n = 7/group): normal control (NC), high-fat diet (HFD), bee bread (HFD + Bb, HFD + 0.5 g/kg/day bee bread) and orlistat (HFD + Or, HFD + 10 mg/kg/day orlistat) groups. After 12 weeks, the HFD group demonstrated significantly higher body weight gain, serum levels of lipids (TG, TC, LDL), liver enzymes (AST, ALT, ALP) and adiponectin, liver lipids (TG, TC) and insulin resistance (HOMA-IR). Furthermore, the HFD group showed significantly decreased antioxidant enzyme activities (GPx, GST, GR, SOD, CAT) and GSH level, and increased liver oxidative stress (TBARS, NO), translocation of Nrf2 to the nucleus, Keap1 expression and inflammation (TNF-α, NF-κβ, MCP-1) together with histopathological alterations (steatosis, hepatocyte hypertrophy, inflammatory cell infiltration, collagen deposition), which indicated the presence of non-alcoholic steatohepatitis (NASH) and fibrosis. Bee bread significantly attenuated all these changes exerted by HFD feeding. In conclusion, our results suggest that bee bread might have antioxidant, anti-inflammatory, anti-steatotic and anti-fibrotic effects that are beneficial in protecting liver progression towards NASH and fibrosis.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an excessive buildup of liver lipids closely associated with various kinds of undesirable metabolic effects and oxidative stress. We aimed to investigate the protective and therapeutic effects of orlistat on metabolic syndrome and oxidative stress parameters in high-fat diet (HFD) induced-MAFLD rats. Twenty-four male Sprague-Dawley rats were randomly divided into four groups (n = 6/group), i.e., Normal control (N), HFD, HFD + orlistat (HFD + O) (10 mg/kg/day administered concomitantly for 12 weeks as a protective model), and obese+orlistat (OB + O) (10 mg/kg/day administered 6 weeks after induction of obesity as a therapeutic model) groups. After 12 weeks, the HFD group had significantly increased Lee obesity index, serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, triglyceride, low-density lipoprotein levels, liver total cholesterol and triglyceride levels, insulin resistance and non-alcoholic steatohepatitis (NASH) together with decreased serum high-density lipoprotein level. Additionally, the HFD group also showed increased Nrf2 translocation to the nucleus with high Keap1 expression and increased liver oxidative stress parameters. Orlistat significantly improved all these alterations in HFD rats. We demonstrated that orlistat might have protective and therapeutic effects against HFD-induced MAFLD rats by its activation on Nrf2 signaling pathway, which subsequently improved metabolic syndrome and oxidative stress parameters.

Colorectal cancer (CRC) represents one of the most common causes of death among cancers worldwide. Its incidence has been increasing among the young population. Many risk factors contribute to the development and progression of CRC and about 70% of them are sporadic. The CRC microenvironment is highly heterogeneous and represents a very complex immunosuppressive platform. Many cytokines and their receptors are vital participants in this immunosuppressive microenvironment. Tumor necrosis factors (TNFs) and TNF receptor 2 (TNFR2) are critical players in the development of CRC. TNFR2 was observed to have increased the immunosuppressive activity of CRC cells via regulatory T cells (T regs) and myeloid-derived suppressor cells (MDSC) in the CRC microenvironment. However, the exact mechanism of TNFR2 in regulating the CRC prognosis remains elusive. Here, we discuss the role of TNFR2 in immune escape mechanism of CRC in the immunosuppressive cells, including Tregs and MDSCs, and the complex signaling pathways that facilitate the development of CRC. It is suggested that extensive studies on TNFR2 downstream signaling must be done, since TNFR2 has a high potential to be developed into a therapeutic agent and cancer biomarker in the future.

Diabetic nephropathy is reported to occur as a result of the interactions between several pathophysiological disturbances, as well as renal oxidative stress and inflammation. We examined the effect of Malaysian propolis (MP), which has anti-hyperglycemic, antioxidant and anti-inflammatory properties, on diabetes-induced nephropathy. Diabetic rats were either treated with distilled water (diabetic control (DC) group), MP (300 mg/kg b.w./day), metformin (300 mg/kg b.w./day) or MP + metformin for four weeks. We found significant increases in serum creatinine, urea and uric acid levels, decreases in serum sodium and chloride levels, and increase in kidney lactate dehydrogenase activity in DC group. Furthermore, malondialdehyde level increased significantly, while kidney antioxidant enzymes activities, glutathione level and total antioxidant capacity decreased significantly in DC group. Similarly, kidney immunoexpression of nuclear factor kappa B, tumor necrosis factor-α, interleukin (IL)-1β and caspase-3 increased significantly, while IL-10 immunoexpression decreased significantly in DC group relative to normal control group. Histopathological observations for DC group corroborated the biochemical data. Intervention with MP, metformin or both significantly mitigated these effects and improved renal function, with the best outcome following the combined therapy. MP attenuates diabetic nephropathy and exhibits combined beneficial effect with metformin.

Oxidative stress contributes to major complications of obesity. This study intended to identify whether orlistat could mitigate myocardial damage in obese animal models. The tested rats were divided into two groups and fed either with normal chow (n = 6 per group) or with a high-fat diet (HFD) for 6 weeks to induce obesity (n = 12 per group). Obese rats were further subjected to treatment either with distilled water (OB group) or orlistat 10 mg/kg/day (OB + OR group). Key indices of oxidative stress, inflammation, and apoptosis were assessed using an immunohistochemical-based technique and real-time PCR. The OB group showed significant increases of oxidative stress markers (TBARs and PCO), with significant decreases of anti-oxidant markers (Nrf2, SOD, CAT, and GPx). Furthermore, mRNA expression of pro-inflammatory markers (TNF-α and NF-κβ) and pro-apoptosis markers (Bax, Caspase-3, Caspase-8, and Caspase-9) were significantly upregulated in the OB group. Obese rats developed pathological changes of myocardial damages as evidenced by the presence of myocardial hypertrophy and inflammatory cells infiltration. Orlistat dampened the progression of myocardial damage in obese rats by ameliorating the oxidative stress, and by inhibiting NF-κβ pathway and caspase-dependent cell apoptosis. Our study proposed that orlistat could potentially mitigate oxidative stress-linked myocardial damage by mitigating inflammation and apoptosis, thus rationalizing its medical usage.