Pushpender Kumar Sharma

Asthma is defined as a chronic airway inflammatory disorder with over-activation of the immune system accompanied by the inability to resolve inflammation. SPMs are novel potent lipid mediators that play an important role in maintaining inflammation homeostasis and macrophages’ functional plasticity. This review will look into the potential function of SPM-programmed macrophage reprogramming as a novel therapeutic strategy for asthma. Unlike current anti-inflammatory treatments, which only focus on suppressing inflammation, SPMs can actively drive the inflammation resolution phase by promoting efferocytosis and wound healing while maintaining the defense against infection. In experimental asthma animal models, lipoxins, resolvins, protectins, and maresins have been demonstrated to alleviate inflammation and airway hyperresponsiveness, shift macrophages towards pro-resolving phenotypes and thus facilitate the resolution process. Levels of some SPM subclasses were found to be reduced in severe or uncontrolled asthmatics, indicating defective resolution pathways may contribute to asthma persistence. The mechanisms include down-regulation of pro-inflammatory cytokines, alteration of macrophage phenotype, improvement of immune homeostasis in the airway milieu, etc. These molecules have become highly promising therapeutic agents after the development of metabolically stable analogs, receptor-targeted agonists, and an improved delivery system. Multi-omics studies coupled with patient stratification based on biomarkers will potentially help in the future to develop personalized resolution-based therapy, in particular for those steroid-resistant and non-type 2 asthmatics. Nevertheless, the evidence provided so far is mainly preclinical; more challenges in terms of pharmacokinetics, formulation and formulation development, regulatory agency approval, and clinical validation remain and will be overcome through further studies, thus warranting investigation into SPM-mediated strategies for asthma and other chronic inflammatory diseases.

Type 2 diabetes mellitus (T2DM) is a multifaceted metabolic disorder marked by impaired insulin action, pancreatic β-cell dysfunction, and the involvement of several interconnected mechanisms, including inflammation, oxidative stress, and epigenetic alterations. Despite progress in conventional therapies, achieving durable glycemic control and minimizing complications remain major challenges. This review discusses the emerging role of bioactive phytochemicals—such as curcumin, berberine, resveratrol, flavonoids, and polysaccharides—in modulating essential molecular pathways including AMPK, PI3K/AKT, and cAMP/PKA, which contribute to enhanced insulin sensitivity, glucose regulation, and β-cell protection. These natural compounds also influence gut microbiota modulation and epigenetic mechanisms, offering additional metabolic and anti-inflammatory benefits. This review synthesizes evidence from peer-reviewed studies published between 2000 and 2024, incorporating bibliometric trends showing an increasing research focus on phytochemicals for T2DM management. However, limitations such as low solubility, instability, and poor absorption restrict their clinical application. Advances in nanotechnology-based delivery systems, including nanoparticles, liposomes, and nanoemulsions, have shown potential to overcome these barriers by improving stability, bioavailability, and targeted delivery of phytochemicals. The integration of gut microbiota modulation with nanocarrier-enabled phytochemical therapy supports a precision medicine approach for managing T2DM. Preliminary clinical evidence highlights significant improvements in glycemic control and inflammatory status, yet further large-scale, well-controlled trials are essential to ensure safety, optimize dosages, and standardize combination regimens. Overall, phytochemical therapies, reinforced by nanotechnology and microbiota modulation, present a promising, safe, and holistic strategy for T2DM management. Continued interdisciplinary research and clinical validation are crucial for translating these advances into effective therapeutic applications and reducing the global diabetes burden.

Introduction: Superoxide Dismutases (SODs) are enzymes that catalyze the conversion of toxic free radicals generated during stress conditions into nontoxic forms. Thus, the enzyme superoxide dismutase contributes to the adaptation and survival of microorganisms across a variety of environmental conditions, making it an indispensable enzyme during the response to stress. In this study, we embarked upon investigating and characterizing a Superoxide Dismutase (SOD) from DNA extracted directly from garden soil, where the average temperature ranges from 4°C- 45°C. Materials and Methods: Metagenomic DNA was extracted by employing a kit. The gene was amplified using PCR. The amplified PCR product was gel eluted and ligated into the pGEMT-easy vector and subcloned into an expression vector. The protein was purified using Ni-NTA chromatography and characterized using biophysical, biochemical, and computational approaches. Results: The recombinant SOD was expressed and purified; the purified protein exhibited activity and stability over a broad pH and temperature range, with optimal activity observed at 40°C and pH 8, respectively. The enzyme remains completely stable at 40°C for 3 h. However, in contrast, it loses 50% of its activity when incubated at 50°C and 60°C for 3 h. The biophysical investigation revealed stable confirmation of the secondary structure of the protein, as evident from circular dichroism and intrinsic Tryptophan (Trp) fluorescence studies. In silico sequence and structural analysis revealed a close similarity of the SOD reported in this study to the Mn SOD of multi- Bacillus species. Molecular simulation dynamics experiments revealed the all-over conformational stability of protein structures at varying pH, indicating broad pH functioning of the enzyme. Discussion: The study provides a comprehensive analysis of the structure and function of a superoxide dismutase enzyme derived from a soil metagenome. A Mn2+ binding site identified in the study offers an opportunity to further facilitate engineering and design of mutant SOD. Conclusion: The enzyme exhibits distinct attributes that hold significant industrial relevance. Owing to the wide functionality of SOD at different pH and temperature, it can be tailored for its potential industrial applications, which include its therapeutic potential, thus opening new avenues for enhanced antioxidant therapies and novel biocatalyst designing.

Anxiety is a widespread psychological disorder affecting both humans and animals. It is a typical stress reaction; however, its longer persistence can cause severe health disorders affecting the day-to-day life activities of individuals. An intriguing facet of the anxiety-related disorder can be addressed better by investigating the role of neurotransmitters in regulating emotions, provoking anxiety, analyzing the cross-talks between neurotransmitters, and, most importantly, identifying the biomarkers of the anxiety. Recent years have witnessed the potential role of the gut microbiota in human health and disorders, including anxiety. Animal models are commonly used to study anxiety disorder as they offer a simpler and more controlled environment than humans. Ultimately, developing new strategies for diagnosing and treating anxiety is of paramount interest to medical scientists. Altogether, this review article shall highlight the intricate mechanisms of anxiety while emphasizing the emerging role of gut microbiota in regulating metabolic pathways through various interaction networks in the host. In addition, the review will foster information about the therapeutic interventions of the anxiety and related disorder. Graphical abstract

The article https://doi.org/10.32388/4BKYAF, titled Decoding the Promiscuous Activity of Bile Salt Hydrolase, is focused on understanding the role of bile salts in acting as substrates as well as forming a micellar environment where bacterial bile sa...