British Journal of Medical and Health Research

Antibiotic resistance is increasing at a super-exponential rate worldwide. Design and approval of new antimicrobial compounds has sunk to the lowest levels in decades. At the current rate of decline in therapeutic effectiveness, the simultaneous emergence of multiple extensively resistant pathogens ("superbugs" or panresistant germs) is projected by this model to occur beyond a critical inefficacy threshold in approximately fourteen years (±3). Untreatable microbes will set back health services globally and will have a profound effect on medical disciplines that invariably need pharmacological control of opportunistic bacteria, such as Oncology and Transplantation medicine (that rely heavily on myelotoxic and/or immunosuppressive drugs), Odontology, Intensive Care, etc. No radically new categories of antibiotics have been discovered for decades. Combinatorial treatments that intend to accentuate antibiotic efficacy may even accelerate the rate of microbial adaptation due to increased selective pressure. Unless new categories of germicidal substances are developed, a reverse epidemiological transition seems inevitable. This paper describes our forecast based on a mathematical model from hard data on the declining effect of antimicrobial medication. Additionally, it suggests an already proven, scalable line of treatment that could overcome microbial resistance.

Extracellular vesicles – more especially, exosomes – have been shown to effective at carrying biomarkers in extracellular environment. The lack of consistency in exosomes separation and analysis technique. limits the use of exosomes in therapeutic environment, despite their great promise .This review objectives are present in many forms of extracellular vesicles, highlight their distinctions and commonalities , go over the various techniques currently employed for exosome extraction and characterization. Exosomal research may become more standardized as a result of a full grasp of the isolation and analysis techniques already in use, making the use of exosomes in clinical settings a possibility. Extracellular vesicles (EVs) are broadly defined as lipid bilayer-enclosed particles released by cells that cannot replicate and are not part of intact cells. EVs include multiple subtypes—exosomes (often ~30–150 nm), microvesicles/ectosomes (typically ~100–1000 nm), apoptotic bodies, and other specialized vesicles—whose boundaries overlap in size, composition, and biogenesis. Because it is often difficult to prove the precise biogenesis route in routine experiments, ISEV recommends using operational terms such as “small EVs” (sEVs) rather than asserting “exosomes” unless endosomal origin is demonstrated [1–3]. Exosomes are explored as disease biomarkers (liquid biopsy), therapeutic carriers (for small molecules, RNA therapeutics, proteins, gene editors), and even as direct therapeutics particularly mesenchymal stromal/stem cell—MSC—derived EVs. “Exosomes” refer to small EVs enriched in endosomal markers and recovered using common sEV workflows. These vesicles are released by immune cells, epithelial cells, stromal cells, neurons, cardiomyocytes, tumor cells, and stem/progenitor cells. They appear in plasma, serum, urine, saliva, cerebrospinal fluid, breast milk, synovial fluid, and bronchoalveolar lavage, among others. Exosomes selectively package proteins, RNAs, lipids, and other molecules depending on cell type, activation state, and environmental cues (hypoxia, inflammation, stress). Once released, exosomes can bind to target cells, fuse with membranes, or be endocytosed, delivering cargo and altering signaling pathways.

Both Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs) are recommended first-line agents for hypertension in patients with Type 2 Diabetes Mellitus (T2DM). However, treatment adherence is frequently compromised by class-specific adverse drug reactions (ADRs). This study compares the safety profiles, tolerability, blood pressure control, and short-term renal outcomes of ACEIs versus ARBs in a clinical setting. Methods: A prospective, observational study was conducted over 12 months in a tertiary care teaching hospital. One hundred adult patients ($N=100$) with T2DM and essential hypertension initiating monotherapy with either an ACEI ($n=50$, e.g., enalapril) or an ARB ($n=50$, e.g., losartan) were enrolled. Baseline demographic, clinical, and laboratory safety markers (serum potassium, serum creatinine, and eGFR) were recorded. Safety endpoints included the incidence of dry cough, hyperkalemia, acute kidney injury (eGFR decline greater than 30%), and therapy discontinuation rates. Efficacy was assessed via blood pressure (BP) and urinary albumin excretion rates. Results: Both groups achieved comparable, statistically significant reductions in systolic and diastolic BP, as well as urinary albumin excretion at 12 months ($p > 0.05$ for inter-group comparisons). However, the ARB group demonstrated a significantly superior safety and tolerability profile. Dry cough was reported in 16% of the ACEI group compared to 0% in the ARB group ($p < 0.01$), leading to a therapy discontinuation rate of 10% in the ACEI cohort. Mild hyperkalemia (serum $K^+ > 5.0 \text{ mEq/L}$) occurred in both groups (ACEI: 8% vs. ARB: 6%; $p > 0.05$) without any severe hyperkalemic events or acute kidney injury. Conclusion: While ACEIs and ARBs provide equivalent blood pressure control and renal protection, ARBs offer a significantly superior safety profile with a lower incidence of dry cough and lower treatment discontinuation rates. ARBs may be preferred as a first-line option to optimize long-term treatment adherence in patients with T2DM and hypertension.