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Natural polysaccharides have attracted considerable interest in pharmaceutical and biomedical applications. However, native polysaccharides often possess limitations, like poor solubility, inadequate mechanical strength, limited stability, and insufficient control over their functional and biological properties. Consequently, structural modification and function-driven reengineering of natural polysaccharides have emerged as important strategies for tailoring the physicochemical and biological characteristics to meet the requirements of advanced pharmaceutical and biomedical systems. Beyond individual modification strategies, polysaccharide reengineering provides a design-oriented framework in which structural features are deliberately tuned to establish relationships between molecular or network architecture, physicochemical properties, biointerfacial interactions, and biological function. This review examines polysaccharide reengineering as a function-driven approach to tailoring the structure and performance of natural polysaccharides. Rather than simply cataloguing modification methods, the review critically connects principal reengineering strategies, including carboxymethylation, sulfation, phosphorylation, grafting, and interpenetrating polymer network (IPN) formation, with their effects on structural characteristics, physicochemical properties, biointerfacial interactions, biological functions, and pharmaceutical performance. Particular emphasis is placed on identifying structure–property–biofunction relationships and on extracting design principles that can guide the selection and combination of reengineering strategies for specific applications. Reengineering of natural polysaccharides provides a versatile strategy to overcome the inherent limitations of native materials and to develop polysaccharide-based platforms with tailored physicochemical and biological properties. Different modification approaches offer distinct functional advantages: carboxymethylation can improve hydrophilicity and pH-responsive swelling, whereas sulfation and phosphorylation introduce anionic functionalities that modulate charge-dependent interactions and biological responses. Similarly, grafting and interpenetrating polymer network (IPN) formation provide greater control over mechanical strength, swelling, stability, drug-loading capacity, and controlled-release behavior. Collectively, these findings demonstrate that the performance of reengineered polysaccharides is determined not by the modification strategy alone, but by the combined effects of the resulting molecular structure, physicochemical characteristics, and interactions with biological environments. Despite these advances, the development of predictable structure-function relationships remains challenging because of variations in polysaccharide source, molecular weight, degree and distribution of modification, and characterization methodologies. Therefore, future research should shift from empirical modification toward rational, function-driven polysaccharide reengineering, in which structural parameters are deliberately controlled to achieve predefined material and biological outcomes. Full article

Heptosyltransferase I (HepI) catalyzes the transfer of L-glycero-D-manno-heptose from ADP-heptose (ADPH) to the inner Kdo₂-lipid A core during lipopolysaccharide (LPS) biosynthesis. This process is essential for outer membrane (OM) integrity in Gram-negative bacteria. As such, HepI represents a promising target for the development of effective antibacterial agents. In this study, an integrated computational approach was employed to identify HepI inhibitor candidates. Four optimized pharmacophore models were subjected to virtual screening against a small-molecule library containing approximately six million compounds prefiltered for physicochemical properties favorable for Gram-negative penetration, followed by molecular docking using MOE, GNINA rescoring, and ADME/drug-likeness profiling to support candidate prioritization. Pharmacophore screening yielded 5, 113, 7146, and 510 unique hits for queries 1–4, respectively. Several compounds showed favorable MOE S-scores compared to the reference ligand AFH (S = −7.83 kcal mol⁻¹), including ZINC000022082637 and ZINC000064971626, with scores of −9.09 and −8.99 kcal mol⁻¹, respectively. GNINA rescoring further showed supportive affinity profiles for selected candidates, including ZINC000019761596, ZINC000001380743, ZINC000014122165, and ZINC000009252534. This approach identified chemically diverse HepI inhibitor candidates from a large Gram-negative-focused compound library. The selected hits showed physicochemical and drug-likeness profiles useful for computational prioritization. As no biochemical or microbiological validation was performed in the present study, these compounds should be regarded as computationally prioritized candidates rather than experimentally confirmed HepI inhibitors. Full article

Background/Objectives: Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease, and cellular senescence is a tractable therapeutic target; yet prioritizing credible repurposing candidates is difficult because bulk-tissue senescence signals are weak, single-dataset analyses are unstable, and transcriptome-reversal screens overstate novelty. The objective was to build a senescence-anchored, multi-evidence computational prioritization of repurposing candidates for DKD entirely from open data. Methods: Per-sample senescence activity was quantified by single-sample gene set enrichment across three DKD kidney cohorts, and consensus signatures were reversed against 45,956 LINCS L1000 signatures. Candidates were ranked by reversal strength, mechanism, ChEMBL stage, and ClinicalTrials.gov novelty, then assessed for robustness by senotherapeutic enrichment, an external senolytic benchmark, leave-one-cohort-out analysis, drug–target Mendelian randomization, and single-nucleus profiling. Results: Senescence activity was consistently elevated in DKD across all three cohorts, with moderate-to-large effect sizes (rank-biserial 0.32–0.78). Reversal recovered established senotherapeutic classes and nominated the approved JAK inhibitor fedratinib (within the same class, baricitinib reduced albuminuria in a Phase 2 DKD trial); curated senolytics were modestly separated from negatives (AUROC 0.62, 95% CI 0.52–0.72). Filtering yielded 867 mechanism-annotated compounds robust to cohort removal. Drug–target Mendelian randomization was inconclusive, and single-nucleus profiling highlighted endothelial activation rather than a stable senescent compartment. Conclusions: The result is an externally benchmarked, novelty-annotated senotherapeutic candidate map, offered as convergent confirmation of repurposable mechanisms rather than a claim of new drug classes. Full article

In the context of the global diabetes epidemic, diabetic nephropathy (DN)—a condition directly associated with diabetes—has become the primary cause of end-stage renal disease, significantly impacting patients’ quality of life and placing substantial demands on public healthcare resources. The pathogenesis of DN is characterized by metabolic disturbances induced by high glucose levels, hemodynamic abnormalities, and the synergistic amplification of various stress signals. These factors collectively contribute to the progressive loss of nephrons and irreversible renal dysfunction. Although current standard treatments can partially slow disease progression, they significantly fail to meet clinical needs. Therefore, there is an urgent necessity to identify multi-target intervention strategies that utilize novel mechanisms of action. Alkaloids, a class of natural nitrogen-containing compounds known for their significant structural diversity, have recently demonstrated multiple renoprotective effects in experimental models of DN. This review is based on a search of the PubMed, Web of Science and CNKI databases. The keywords alkaloids, diabetic nephropathy, diabetic nephropathies, diabetic kidney disease, inflammation, oxidative stress, fibrosis, autophagy and apoptosis were used to search for original research articles in both Chinese and English, published between 2010 and 2026, which investigated the mechanisms by which alkaloid compounds exert their anti-DN effects. Focusing on anti-inflammatory effects, anti-oxidative stress, anti-renal fibrosis, autophagy modulation, apoptosis regulation and ferroptosis inhibition, the review then summarized the relevant literature by systematizing the experimental models, intervention protocols, dosages and key results. This provided a new theoretical perspective and experimental basis for the clinical translation and new drug development of alkaloid compounds for the treatment of DN. The review provides a new theoretical perspective and an experimental basis for the clinical translation of, and new drug development based on, alkaloid compounds for the treatment of DN. Full article

Background/Objectives: Pancreatic cancer (PC) is a leading cause of cancer-related death in the United States and lacks efficient therapeutic options. Serine peptidase inhibitor, clade B, member 5 (SERPINB5) is non-inhibitory toward serine proteases, yet it has diverse biological functions, including regulating cell migration, cell death, gene expression, and stress responses. Mesothelin (MSLN) is a tumor-associated antigen that is broadly overexpressed on various malignant tumor cells and plays a crucial role in promoting proliferation, invasion, and metastasis. Methods: We integrated public database analyses, cell-line screening, gene knockdown and overexpression, immunoblotting, cell viability and apoptosis assays, flow cytometry, chromatin immunoprecipitation paired with quantitative PCR (ChIP-qPCR), and chimeric antigen receptor (CAR) T-cell therapy to investigate SERPINB5 and MSLN functions, developing a novel and effective therapeutic strategy for patients with pancreatic cancer. Results: Both SERPINB5 and MSLN are highly expressed and negatively associated with the overall survival of PC patients. Our mechanistic study suggests that SERPINB5 negatively regulates the mitochondrial protein dehydrogenase/reductase 2 (DHRS2) to promote PC cell survival; consequently, SERPINB5 depletion induces PC cell apoptosis. Of note, SERPINB5 depletion increases MSLN transcription by enhancing c-Myc binding to the MSLN promoter region, which in turn suppresses the mitochondrial protein DHRS2 and leads to resistance to apoptosis in PC cells. Our genetic ablation study shows that SERPINB5 and MSLN are critical for PC cell survival, and that depleting both proteins synergistically induces PC cell apoptosis. Gemcitabine (GEM) is a standard chemotherapy drug for PC treatment. Our study shows that SERPINB5-high PC cells display greater sensitivity to GEM than SERPINB5-low PC cells. GEM treatment increases mitochondrial DHRS2 protein expression, similar to the effect of SERPINB5 knockdown, whereas upregulated MSLN confers apoptotic resistance by decreasing DHRS2 levels. Conclusions: Our in vitro study demonstrates that sequential treatment with GEM followed by anti-MSLN chimeric antigen receptor (CAR)-T cells is an effective and promising strategy for patients with pancreatic cancer. Future studies using mouse models may validate the efficacy of this sequential treatment strategy in vivo. Full article

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the management of obesity and type 2 diabetes mellitus (T2DM). Although randomized clinical trials have demonstrated substantial weight loss and metabolic benefits with incretin-based therapies, real-world evidence is needed to characterize anthropometric outcomes, safety, prescribing patterns, and treatment use under routine clinical conditions. Objectives: The objective of this study was to characterize real-world anthropometric outcomes, safety, and use patterns of GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists in patients with obesity or glucose metabolism disorder receiving treatment through Spanish community pharmacies. Methods: A nationwide multicentre cross-sectional study with retrospective data collection was conducted between January and April 2026 across community pharmacies in Spain. Adult patients receiving GLP-1 receptor agonists or dual GIP/GLP-1 receptor agonists were consecutively enrolled and classified according to therapeutic indication (obesity or glucose metabolism disorder). Changes in body weight and body mass index (BMI) were assessed using paired-sample t-tests, while multivariable linear regression explored independent determinants of weight loss. Crude safety signals were initially evaluated using exploratory crude safety association analysis based on Odds Ratios (ORs). Subsequently, multivariable logistic regression was performed to identify independent predictors of suspected digestive adverse drug reactions after adjustment for demographic characteristics, treatment-related variables, lifestyle factors, and concomitant glucose-lowering therapies. Baseline body weight was retrospectively reported by participants and was not independently verified against clinical records or other objective sources, whereas current body weight was measured by the pharmacist at the study visit. Results: A total of 531 patients were included (52.2% with obesity; 47.8% were classified in the glucose metabolism disorder (GMD) cohort, comprising 200 patients with type 2 diabetes mellitus and 54 with prediabetes/fasting glucose disturbance; the mean age was 56.5 ± 12.5 years; and 66.7% were women). The mean observed reduction in body weight from treatment initiation to the study assessment was 12.17 ± 10.64 kg, corresponding to an 11.71% ± 9.40% reduction relative to retrospectively reported baseline weight. Overall, 73.9% and 54.1% of participants achieved ≥5% and ≥10% weight loss, respectively. No statistically significant unadjusted difference in relative weight loss was detected across treatment groups; however, equivalence was not formally assessed. Gastrointestinal suspected adverse drug reactions were the most frequently reported safety outcomes. Exploratory crude analyses showed nominal associations between Wegovy^® and nausea/vomiting and between Mounjaro^® and constipation, as well as between concomitant insulin and dizziness and SGLT2 inhibitor therapy and urinary disorders; however, none of these associations remained statistically significant after Benjamini–Hochberg correction for multiple testing. In the exploratory multivariable linear regression model, treatment duration, treatment agent, dietary adherence, light physical activity, and age showed statistically significant adjusted associations with observed percentage weight loss. In the multivariable logistic regression model, increasing age was the only variable significantly associated with lower odds of reported suspected digestive adverse drug reactions (adjusted OR = 0.97 per year; 95% CI 0.96–0.99; p = 0.003). Conclusions: Observed percentage weight loss varied across treatment groups, although between-treatment comparisons should be interpreted cautiously because of differences in treatment duration, therapeutic indication, sample size, and dose exposure. Given the retrospective ascertainment of baseline weight and the cross-sectional design, these findings should be interpreted as real-world estimates of observed weight change rather than causal estimates of treatment effectiveness. Reported suspected adverse drug reactions were common, particularly gastrointestinal events. Although several nominal associations were observed in exploratory crude analyses, none remained statistically significant after correction for multiple testing. These findings support the importance of individualized monitoring in community pharmacy settings. These findings provide a rationale for the prospective development and evaluation of a standardized pharmacy-led dispensing and follow-up protocol to support patient safety and treatment adherence. Full article

Introduction: Diabetic painful neuropathy (DPN) is one of the most common and debilitating complications of diabetes, substantially impairing the quality of life of patients. In the absence of disease-modifying therapies, treatment remains focused on symptomatic pain control with non-opioid pharmacologic agents; however, comparative evidence guiding optimal medication selection remains limited. Using a systematic review, pairwise meta-analysis, and network meta-analysis, this study compares the effectiveness of current non-opioid-based treatments, including amitriptyline, duloxetine, gabapentin, and pregabalin, for pain reduction in patients with DPN. Methods: PubMed and Google Scholar were systematically searched for randomized and clinical trials published between 2010 and 2025 evaluating these medications as monotherapy for DPN. A total of n = 11 studies met the inclusion criteria. Pain outcomes measured using the Numeric Rating Scale (NRS), Visual Analog Scale (VAS), or Brief Pain Inventory (BPI) were standardized to a common metric. Random-effects pairwise meta-analyses were performed to estimate within-drug treatment effects, followed by a frequentist network meta-analysis to compare therapies through direct and indirect evidence. Mean change in pain severity was the primary outcome. We performed heterogeneity, network consistency, and sensitivity analyses under varying correlation assumptions. Results: A total of 1397 participants across 11 studies were included. Pairwise meta-analysis demonstrated substantial pain reduction with duloxetine (mean change [MC] 27.8; 95% CI 18.5–37.1), gabapentin (MC 34.8; 95% CI 9.3–60.3), and pregabalin (MC 19.7; 95% CI 8.9–30.5). Although amitriptyline trials individually reported improvement, the pooled estimate did not reach statistical significance. Network meta-analysis indicated that gabapentin, duloxetine, and amitriptyline were associated with better estimated analgesic benefit than pregabalin; the differences among gabapentin, duloxetine, and amitriptyline were modest and not statistically significant. Sensitivity analyses supported the robustness of the findings, and no significant network inconsistency was detected. Conclusions: Commonly used non-opioid pharmacologic therapies for DPN provide broadly comparable analgesic benefit, with gabapentin showing comparatively preferable reduction in pain severity within the network analysis. Given the modest differences between agents and substantial variability in individual response, treatment decisions should be individualized according to patient comorbidities, tolerability, and therapeutic goals. Larger, methodologically standardized comparative trials are needed to strengthen the evidence base and support more precise, evidence-based management of DPN. Full article

Pancreatic diseases, particularly pancreatic ductal adenocarcinoma (PDAC), remain among the most challenging disorders to diagnose and treat owing to a series of interconnected biological barriers, including dense stromal desmoplasia, profound immunosuppression, hypoxia, therapeutic resistance, and the lack of effective early-detection strategies. Overcoming these barriers requires multifunctional platforms capable of integrating diagnosis, microenvironment regulation, and precision therapy within a single system. Metal–organic frameworks (MOFs), a class of highly tunable porous crystalline materials, have emerged as uniquely suited candidates for this purpose because of their programmable composition, structural versatility, catalytic activity, and capacity for multifunctional integration. Notably, MOFs have evolved from passive drug carriers into active regulators of disease-associated biological processes, enabling enhanced drug delivery, extracellular matrix remodeling, ferroptosis- and cuproptosis-based precision therapy, energy-triggered reactive oxygen species generation, immune microenvironment reprogramming, and imaging-guided theranostics. Beyond pancreatic cancer, emerging evidence further supports their potential applications in pancreatitis management and interventional therapeutic enhancement. In this review, we systematically summarize recent advances in the rational engineering of MOFs for pancreatic diseases, focusing on how material design strategies are leveraged to overcome key pathological barriers and improve therapeutic outcomes. We further discuss current challenges associated with biosafety, biodegradation, large-scale manufacturing, and clinical translation, while highlighting future opportunities for the development of next-generation MOF-based precision nanomedicines. By integrating advances across materials science, nanomedicine, and pancreatic disease biology, this review provides a comprehensive framework for the design and translational development of MOF-enabled diagnostic and therapeutic platforms. Full article

In the present era, modern drug delivery systems play a fundamental role in ensuring the systematic delivery of the drug into the body, reaching the desired targets. Across recent decades, the drug delivery system has evolved from simple oral and injectable formulations to interpolating with various developed techniques to fabricate innovative treatment approaches for safer, effective, and better patient compliance. Progressive techniques like nanoparticles, microparticles, liposomes, polymer-based systems, 3D printing, and biological carriers have been extensively combined with specifically targeted drug-delivery techniques across infectious, oncological, pulmonary, and neurological conditions. Microneedle transdermal patches have advanced in tandem. They have gained attention for their advancement to surpass the stratum corneum, minimal invasiveness, independent delivery, and patient compliance. This review provides a translational perspective by integrating MN materials and device engineering with drug-delivery performance, patient usability, clinical evidence, manufacturing scalability, and regulatory considerations to examine the progression of MN technologies from laboratory development toward real-world healthcare implementation. Microneedles are fabricated in different types, such as solid, coated, hollow, dissolving, and hydrogel-based, to enhance precision in dosing, better permeability, and suitability across diverse populations, and complex molecules are designed, such as proteins, peptides, hormones, vaccines, and cosmetic agents. Moreover, studies suggest MN are widely accepted by geriatric and pediatric groups, reduce anxiety, and significantly benefit individuals with trypanophobia, swallowing difficulties in the case of oral doses, and compromised venous action, in addition to breaking social inequity. MN-induced microchannels can transiently increase skin permeability and may facilitate sustained or controlled drug delivery depending on MN geometry, formulation, application conditions, skin site, and individual skin characteristics. The persistence of these microchannels and their safety profile are dependent on both device and formulation characteristics. MN is a pivotal part of the novel drug delivery system, addresses the complications arising due to conventional drug delivery, and proves to focus on the improvement of pharmacokinetic parameters, patient-centric therapy, target delivery, and real-world accessibility. Further transformation in the enhancement of MN technology can lead to clinically promising drug delivery systems for the management of long-term treatment and boost next-generation therapies. Full article

Right-sided infective endocarditis (RSIE) is a difficult clinical problem, particularly among people who inject drugs (PWID), in whom large tricuspid vegetations may be complicated by severe regurgitation and septic pulmonary embolization. We describe a woman in her twenties with tricuspid valve infective endocarditis and bilateral cavitary pulmonary lesions consistent with septic emboli, in whom the vegetation enlarged from 18 × 11 mm to 18 × 20 mm and tricuspid regurgitation (TR) progressed from moderate to severe (vena contracta 12 mm, effective regurgitant orifice area 1.5 cm², regurgitant volume 110 mL) over ten days of empirical anti-staphylococcal therapy. Surgery was considered by an individualized Heart Team assessment of the complete clinical course, but the patient declined open-heart surgery. After multidisciplinary Heart Team discussion, transesophageal echocardiography (TEE)-guided percutaneous aspiration with the AngioVac system was undertaken as an individualized debulking and source-control strategy, not as an equivalent alternative to surgery. Under general anesthesia, bilateral femoral venous access was obtained and seven aspiration passes retrieved four large vegetation fragments, with no residual intracardiac mass on completion TEE. Culture of the aspirated material yielded Serratia marcescens and Escherichia coli, neither of which was covered by the empirical regimen, which was replaced by susceptibility-guided ciprofloxacin and co-trimoxazole; ceftazidime was added when Pseudomonas aeruginosa was later isolated from blood. Residual regurgitation arose from a flail, prolapsing posterior leaflet rather than from mass effect—a finding that may reflect pre-existing infective leaflet destruction, leaflet injury during aspiration, or both—and was quantitatively reduced three to four weeks after the procedure (vena contracta 6 mm, effective regurgitant orifice area 0.55 cm², regurgitant volume 36 mL); at six months it was moderate-to-severe and stable, with preserved right ventricular function (TAPSE 30 mm) and no recurrent vegetation. This case supports a potential diagnostic and therapeutic role for AngioVac-assisted debulking as an individualized adjunct in highly selected patients with RSIE who refuse surgery, with the caveat that aspiration reduces vegetation and embolic burden without correcting the underlying valvular lesion. Full article

Therapeutic resistance remains a major limitation in T-cell acute lymphoblastic leukemia (T-ALL) and can reduce the efficacy of chemotherapeutic agents, including doxorubicin (DOXO). Since intracellular drug accumulation and retention are important determinants of DOXO activity, we evaluated whether its encapsulation in a β-cyclodextrin (β-CD)-based carrier could improve its intracellular behavior in resistant leukemia cells. β-CD was functionalized with D-α-tocopherol succinate (TOCO), characterized by FTIR and ¹H NMR, and subsequently used for DOXO encapsulation. The selected β-CD-TOCO formulation exhibited a hydrodynamic diameter of approximately 100 nm, a PDI below 0.4, and a ζ-potential near −20 mV. DOXO encapsulation efficiency increased from 8.76 ± 0.41% in non-functionalized β-CD to 11.54 ± 0.51% after TOCO functionalization, while loading capacity increased from 1.06 ± 0.04% to 1.15 ± 0.05%. The biological effects of the formulation were examined in Jurkat cells as a chemoresistant T-ALL model. Encapsulation did not prevent DOXO incorporation into the cells but increased its intracellular retention and modified its subcellular distribution. In particular, encapsulated DOXO showed greater nuclear accumulation, with a nucleus-to-cytosol fluorescence ratio of 2.58 compared with 1.02 for free DOXO. The increased intracellular persistence of DOXO was accompanied by reduced metabolic activity, increased Annexin V labeling, and greater cytotoxicity than that produced by the free drug. These results show that β-CD-mediated encapsulation can modify the intracellular disposition of DOXO and increase its activity in chemoresistant T-ALL cells. The β-CD-TOCO system therefore provides a basis for further evaluation of DOXO delivery in additional models of resistant lymphoid leukemia. Full article

Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection remains a major public health concern globally and in the Philippines. The country continues to face a high burden of TB, multidrug- and rifampicin-resistant TB (MDR/RR-TB), HIV, and HIV-associated TB. Since HIV increases the risk of TB and TB worsens HIV outcomes, co-infection hinders progress toward the End TB Strategy and the UNAIDS 95-95-95 targets. This review summarizes the current knowledge on the epidemiology, prevention, and treatment of TB–HIV co-infection with a focus on the Philippine setting. Key challenges include socioeconomic barriers to care and rising drug resistance. In addition, the lack of an integrated TB–HIV data system disrupts continuity of care and weakens surveillance. Closing these gaps requires a coordinated national response that integrates effective policy with active community engagement. Research-driven and locally adapted strategies will be essential to bring the Philippines closer to its elimination goals. Full article

Herpes simplex virus type 1 (HSV-1) and varicella–zoster virus (VZV) are clinically important alphaherpesviruses that establish lifelong latent infections and remain significant causes of morbidity despite the availability of antiviral drugs. The emergence of drug resistance and the inability of current therapies to eliminate latent virus reservoirs underscore the need for novel antiviral agents with alternative mechanisms of action. In the present study, we evaluated the antiviral activity of an ethanolic extract prepared from commercial cinnamon bark marketed as Cinnamomum cassia and cinnamaldehyde, a well-known constituent of cinnamon tested here as a purified compound, against HSV-1 and VZV in vitro. Antiviral activity was assessed using plaque reduction assays, time-of-addition experiments, and quantitative real-time PCR for viral DNA accumulation and specific viral immediate-early transcript levels. Both the C. cassia extract and cinnamaldehyde inhibited HSV-1 and VZV replication in a dose-dependent manner while exhibiting relatively low cytotoxicity. Nonlinear dose–response analysis yielded IC₅₀ values of 3.44 and 2.80 µg/mL for the C. cassia extract against HSV-1 and VZV, respectively, and 0.961 and 1.50 µg/mL for cinnamaldehyde. Time-of-addition experiments demonstrated that antiviral activity was greatest when treatment was maintained throughout infection or initiated after viral entry, whereas pretreatment of cells or direct incubation with virus particles produced minimal effects. Both agents markedly reduced intracellular production of infectious progeny viruses and decreased viral DNA accumulation and the abundance of the specific immediate-early transcripts examined. These findings support a predominantly post-entry antiviral effect of both materials, rather than a primary effect on viral attachment or direct virion inactivation. Collectively, these results support further investigation of these agents as promising natural inhibitors of HSV and VZV infections. Full article

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disorder characterized by recurrent nodules, abscesses, and sinus tract formation, driven by dysregulated innate immunity and microbial dysbiosis. Intravenous ertapenem has emerged as a therapeutic option for severe, refractory HS, with clinical studies consistently demonstrating meaningful improvements in pain, drainage, inflammatory markers, and quality of life. While these benefits have traditionally been attributed to ertapenem’s broad-spectrum antimicrobial activity against the polymicrobial anaerobic flora of HS lesions, the rapid onset of clinical improvement and inconsistent anaerobic suppression observed during treatment suggest that additional mechanisms may be at play. Emerging mechanistic evidence from studies of carbapenems in non-HS experimental systems suggests that this drug class may influence host inflammatory pathways through effects on cytokine signaling, endotoxin release, neutrophil and macrophage activation, and NF-κB inhibition. Additionally, ertapenem’s unusually high plasma protein binding, particularly to acute-phase reactants elevated in HS such as haptoglobin and fibrinogen, may further influence drug distribution and immune signaling within inflamed tissues. This review examines the antimicrobial and emerging immunomodulatory properties of ertapenem and explores how these convergent mechanisms may explain its clinical efficacy in severe HS, while highlighting stewardship considerations and directions for future research. Methods: A structured search of PubMed/MEDLINE was conducted from database inception through 1 May 2026 using terms related to hidradenitis suppurativa, ertapenem, carbapenems, antimicrobial activity, immunomodulation, inflammatory signaling, innate immune cells, and pharmacokinetics. During revision, a targeted literature update through 1 September 2026 was performed to incorporate newly published and reviewer-requested studies. Eligible clinical, microbiologic, pharmacologic, and mechanistic studies were screened by title, abstract, and full text and synthesized narratively. Full article

Antimicrobial resistance (AMR) is a major global health threat that erodes the effectiveness of antibiotics and increases morbidity, mortality, and healthcare costs. Updated forecasts project that bacterial AMR could directly cause approximately 39 million deaths between 2025 and 2050, with annual deaths rising from 1.14 million in 2021 to an estimated 1.91 million in 2050; earlier economic modelling placed the cumulative cost of unchecked resistance at up to 100 trillion United States dollars. These figures underscore the need for sustainable alternatives to conventional antibiotics. This review synthesizes current evidence on non-antibiotic strategies, including bacteriophages, antimicrobial peptides, CRISPR-based antimicrobials, microbiome modulation, host-directed therapies, nanotechnology, and artificial-intelligence-driven drug discovery. We searched more than one hundred peer-reviewed studies, clinical trial reports, primary epidemiological analyses, and international policy and regulatory documents to evaluate therapeutic mechanisms, clinical progress, and implementation barriers, with particular attention to which strategies suit personalized, patient-specific application and which are more amenable to standardized mass production. Bacteriophages and antimicrobial peptides show potent broad-spectrum activity with reduced resistance selection pressure, CRISPR-based approaches enable precise pathogen targeting, and microbiome therapies restore colonization resistance. Clinical translation, however, is hindered by inconsistent regulatory frameworks, limited manufacturing scalability, incomplete safety profiles, and constrained funding in low-resource settings. Mitigating the AMR crisis will require a coordinated, multidisciplinary response grounded in the One Health paradigm, emphasizing antimicrobial stewardship, equitable global access to emerging therapeutics, and sustained investment in translational research. Full article