Background: Chronic hepatitis B virus (HBV) infection is a well-recognized cause of hepatic injury through prolonged viral replication, inflammation, and oxidative stress. Existing antiviral drugs limit viral replication but cannot eliminate viral transcription or even totally preclude liver injury, thus reemphasizing the significance of drugs with combined antiviral and hepatoprotective effects. Objectives: To evaluate the effects of wedelolactone on HBV replication, gene expression, inflammation, and oxidative stress in an in-vitro model of HBV plasmid transfection with human hepatic cells. Methods: Human hepatocellular carcinoma cells (Huh7) were transfected with a 1.3-mer plasmid and treated with wedelolactone (2.5 - 10 µM). Luciferase assays for HBV promoter activity, Northern blotting and Southern blotting for transcripts and replicative intermediates, qPCR for extracellular HBV DNA, and western blotting for viral antigens such as HBx were performed. Cell cytotoxicity was measured. NF-κB/IκB, inflammatory cytokines (TNF-α, IL-6), and antioxidant markers (Nrf2, HO-1, Keap1) were assessed to evaluate inflammatory and oxidative responses. Results: Wedelolactone significantly suppresses HBV promoter activity, RNAs, core particle formation, and extracellular HBV DNA. It reduced the expression of HBcAg and HBsAg. It inhibited NF-κB activation and cytokine release, while simultaneously enhancing Nrf2/HO-1 signaling, including induction of heme oxygenase-1 by lowering levels of Keap1. Conclusions: Wedelolactone exerts dual antiviral and hepatoprotective actions by inhibiting HBV replication and modulating inflammatory and oxidative stress pathways.

Urinary tract infections are among the most common bacterial infections encountered in clinical practice, with Escherichia coli representing the dominant urinary pathogen. Increasing detection of multidrug-resistant and extended-spectrum beta-lactamase (ESBL)-producing uropathogens has narrowed empirical treatment options and renewed interest in fosfomycin. However, local long-term surveillance data on fosfomycin susceptibility remain limited in Pakistan. This study evaluated temporal changes in major urinary isolate categories and fosfomycin susceptibility patterns within a diagnostic laboratory network in Pakistan from 2013 to 2025. An exploratory molecular sub-analysis was also performed to assess selected resistance-associated transcript patterns in archived fosfomycin-susceptible and fosfomycin-resistant isolates. A retrospective laboratory-based, isolate-level analysis was conducted using anonymized urine culture records. The source database included 34,230 urine sample records, from which eligible culture-positive urinary isolates with required organism classification and fosfomycin susceptibility data were included in the final analytical dataset. Analyses were performed across predefined mutually exclusive study intervals. Organism categories included non-ESBL E. coli, ESBL-producing E. coli, laboratory-coded ESBL E. coli 24 variant, Klebsiella spp., and Enterococcus spp. The ESBL E. coli 24 variant was treated as a laboratory reporting category, not as a genomically confirmed clone or sequence type. Fosfomycin resistance was evaluated using interval-based comparisons and odds ratios. A selected subset of 24 archived isolates, including fosfomycin-susceptible and fosfomycin-resistant E. coli and Klebsiella pneumoniae, was analyzed by RT-qPCR for glpT, uhpT, murA, fosA, fosA3, and blaCTX-M transcript abundance. The final isolate-level analytical dataset included 17,978 eligible urinary isolates. Among urine records with available sex data, female-associated records represented the majority throughout the study period, but this finding reflects laboratory record distribution rather than patient-level UTI prevalence. E. coli remained the predominant urinary isolate category. Non-ESBL E. coli declined across study intervals, whereas ESBL-associated E. coli categories represented a larger proportion of isolates in later years. The laboratory-coded ESBL E. coli 24 variant increased in later intervals, although this finding requires cautious interpretation because confirmatory molecular typing was not performed. Fosfomycin resistance showed a non-linear temporal pattern: resistance decreased from the early to the middle interval and then increased markedly to 23.8% during 2021-2025, while susceptibility declined to 60.6% in the same interval. Compared with the middle interval, isolates from 2021-2025 had higher odds of fosfomycin resistance (OR = 3.64, 95% CI: 3.23-4.12; p < 0.001). In the exploratory molecular subset, resistant isolates showed lower transcript abundance of selected uptake-associated genes, particularly glpT and uhpT, and higher expression of selected fosfomycin- and ESBL-associated genes, including fosA, fosA3, and blaCTX-M. These findings represent transcriptional associations in selected isolates and do not establish definitive resistance mechanisms. Urinary isolates in this diagnostic-network dataset showed a temporal shift toward greater representation of laboratory-reported ESBL-associated E. coli categories and a marked increase in fosfomycin resistance during 2021-2025. The findings support continued local surveillance of urinary pathogens and periodic reassessment of fosfomycin susceptibility for antimicrobial-stewardship guidance. The molecular findings should be interpreted as exploratory transcriptional observations because they were based on a small selected isolate subset and were not supported by genomic, mutational, uptake, or functional validation.

Background Glycated hemoglobin (HbA1c) is a widely used indicator of chronic glycemic exposure and is central to diabetes diagnosis, monitoring, and prevention of microvascular and macrovascular complications. Because diabetes affects multiple organ systems, interpretation of HbA1c may be strengthened when renal, hepatic, and lipid biomarkers are assessed concurrently. Objective This study evaluated the age- and sex-stratified distribution of HbA1c-tested diabetic patients between 2019 and 2022 and explored the relationship between poor glycemic control and selected renal, hepatic, and lipid biomarkers in the 2022 dataset. Methods A retrospective cross-sectional laboratory analysis was performed using anonymized patient records from 2019–2022. Patients were stratified into three age categories (< 30, 30–60, and > 60 years) and by sex. For 2022, additional biomarkers, including micro-creatinine ratio, urea, creatinine/glomerular filtration rate (GFR) ratio, uric acid, bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, albumin, total protein, cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, and very-low-density lipoprotein, were summarized according to age and sex. Descriptive analysis was used to identify year-wise demographic patterns and biomarker abnormalities associated with elevated HbA1c. Results The dataset showed a persistent burden of abnormal HbA1c across adult age groups. The 30-60-year age band contributed the largest number of HbA1c records in 2020 and 2021, whereas the > 60-year group was prominent in 2022. In the 2022 biomarker subset, abnormal renal markers, dyslipidemia, and liver enzyme variations were observed among patients with elevated HbA1c. Younger males showed a high proportion of abnormal cholesterol and triglyceride results, while younger females showed comparatively higher abnormal urea, uric acid, and alanine aminotransferase proportions. These findings support the clinical value of paired HbA1c-biomarker monitoring. Conclusion The study emphasizes that HbA1c should not be interpreted in isolation in patients with diabetes. Combined assessment with renal, hepatic, and lipid biomarkers may improve early recognition of diabetic complications and guide personalized care. Larger patient-level analyses with standardized denominators are recommended to confirm the observed patterns.

Background: Chronic liver injury progressively induces fibrotic remodeling through persistent inflammatory activity and aberrant extracellular matrix accumulation. Growing evidence indicates that this process involves not only intrahepatic signaling but also gut–liver crosstalk and sirtuin-regulated inflammatory pathways. Hesperetin, a citrus-derived flavanone with reported antioxidant and anti-inflammatory properties, has not been adequately evaluated with respect to microbiota-associated changes and SIRT2-associated signaling during fibrotic liver injury. Objectives: This study investigated whether hesperetin attenuates CCl4-induced liver fibrosis in mice by modulating selected gut microbial populations and suppressing SIRT2-associated inflammatory signaling pathways. Methods: Male mice were randomly assigned to the vehicle, CCl4, and CCl4 + hesperetin groups (n = 5 per group). Liver fibrosis was induced by intraperitoneal administration of CCl4 twice weekly for six weeks, and hesperetin was administered orally at 100 mg/kg/day. Histological, biochemical, inflammatory, SIRT2-associated, and selected gut microbial endpoints were assessed. The expression levels of α-SMA, TGF-β1, TNF-α, IL-6, and SIRT2 were quantitatively analyzed using quantitative polymerase chain reaction (qPCR), Western blotting, and an enzyme-linked immunosorbent assay (ELISA). Levels of selected gut microflora were measured using targeted qPCR for Firmicutes, Bacteroidetes, Akkermansia, and Escherichia coli. Results: CCl4 exposure increased collagen deposition, collagen proportionate area (CPA), and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, indicating fibrotic remodeling and hepatocellular injury. Hesperetin treatment significantly decreased collagen deposition and CPA and partially normalized ALT and AST activities compared with CCl4 treatment alone. Fibrosis biomarkers, including α-SMA and TGF-β1, and inflammatory cytokines, including TNF-α and IL-6, showed significant decreases in expression at both the mRNA and protein levels. Hesperetin reduced CCl4-associated SIRT2 upregulation and restored acetyl-α-tubulin levels, suggesting attenuation of SIRT2-associated deacetylase activity. Conclusions: These exploratory findings suggest that hesperetin attenuates CCl4-induced liver fibrosis by reducing collagen accumulation and biochemical liver injury, suppressing inflammatory and fibrogenic signaling, modulating selected gut microbial populations, and regulating SIRT2-associated acetylation signaling.

Pseudomonas aeruginosa pneumonia is characterized by excessive inflammation, oxidative damage, and virulence-driven epithelial injury. Targeting host inflammatory and antioxidant pathways, alongside bacterial virulence factors, may offer a complementary strategy to mitigate infection-induced damage. Curcumin, a bioactive compound from Curcuma longa, possesses established anti-inflammatory and antioxidant properties, but its effects on epithelial responses during bacterial infection remain incompletely defined. This study evaluated the impact of curcumin on NF-κB and Nrf2 signaling, inflammatory and oxidative responses, bacterial virulence, and epithelial repair in a cell-based model of P. aeruginosa–induced airway injury. Human bronchial epithelial BEAS-2B cells were pretreated with curcumin (10 µM) prior to infection with P. aeruginosa (1 × 10⁷ CFU/mL; MOI = 10). Cell viability, oxidative stress, cytokine production, bacterial load, and epithelial regeneration were assessed using MTT, DCFDA, qPCR, ELISA, while Western blotting and confocal microscopy characterized molecular and morphological changes. Curcumin pretreatment improved cell viability ( 87

Background: Nicotinamide adenine dinucleotide (NAD⁺) is a pivotal coenzyme and signaling substrate that integrates redox balance with mitochondrial energy production, DNA repair, epigenetic control, and cellular stress resilience. Declines in NAD⁺ availability—frequently observed with ageing, chronic inflammation, and metabolic stress—have intensified interest in NAD⁺ restoration as a potential strategy to influence disease biology across multiple organ systems. Objective: This narrative review summarizes contemporary mechanistic and translational evidence on NAD⁺ biosynthesis and turnover, highlighting the de novo kynurenine pathway and vitamin B3–dependent salvage routes (nicotinic acid, nicotinamide, nicotinamide riboside, and nicotinamide mononucleotide). We also examine how major NAD⁺ consumers and sensors, sirtuins, poly(ADP-ribose) polymerases (PARPs), and CD38 link NAD⁺ status to inflammation, oxidative stress, and tissue dysfunction in diverse clinical contexts. Methods: Peer-reviewed literature on NAD⁺ metabolism, NAD⁺-dependent signaling, and preclinical/clinical studies of NAD⁺ precursors was evaluated and organized into: (i) core biochemical functions in cellular energetics, (ii) NAD⁺ consumption in genome maintenance and immune signaling, and (iii) organ-focused evidence relevant to skin disorders, infertility and reproductive health, osteoarthritis, hearing loss, vision decline, gut barrier dysfunction, cardiovascular and renal metabolism, hepatic steatosis, neurological diseases, and skeletal muscle health. Results: NAD⁺ supports glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation, while acting as an essential substrate for PARP-driven DNA repair and sirtuin-mediated deacylation programs that shape mitochondrial fitness, inflammatory tone, and metabolic flexibility. Across experimental models, impaired NAD⁺ homeostasis repeatedly associates with mitochondrial dysfunction, heightened oxidative injury, and dysregulated immune–barrier responses, features shared by intestinal inflammation, neurodegeneration and ischemic injury, cardiometabolic disease, kidney injury, and fatty liver disease. Supplementation with NAD⁺ precursors (notably NR and NMN) reliably elevates NAD⁺ in preclinical systems and increases circulating NAD⁺ metabolites in humans, with early signals of pathway engagement; however, clinical outcomes remain heterogeneous across populations, dosing regimens, and endpoints. Evidence for intravenous NAD⁺ “drip” therapy is comparatively limited and insufficiently standardized, with constraints related to tolerability, dose consistency, and cost, underscoring the need for controlled trials. Conclusion: NAD⁺ occupies a central position at the interface of energy metabolism, genome integrity, and immunometabolic signaling, providing a coherent framework for understanding how cellular stress can propagate multisystem dysfunction. Although NAD⁺-boosting strategies are biologically plausible and mechanistically supported, definitive clinical benefit across skin, fertility, osteoarthritis, sensory decline, gut disorders, cardiovascular and hepatic disease, neurological conditions, and muscle health will require well-designed human studies with standardized biomarkers, safety surveillance, and clinically meaningful endpoints.

Objective(s)Hepatitis B virus (HBV) replication is tightly controlled by host stress and innate immune pathways. The small noncoding RNA nc886 (vtRNA2-1) is a known endogenous inhibitor of protein kinase R (PKR), but its role in HBV biology remains unclear. This study aimed to define the function of the nc886–PKR–eIF2α axis in HBV-replicating hepatoma cells and to determine whether nc886 depletion suppresses HBV replication via PKR-dependent translational control.Materials and methodsHuh7 cells and Huh7 cells stably harboring a 1.3-mer HBV replicon were used. Endogenous nc886 and PKR expression was assessed by RT-qPCR and Western blot. Loss-of-function experiments employed two independent siRNAs against nc886 and one siRNA against PKR, alone or in combination, with scramble siRNA as control. PKR activation was induced by Poly(I:C); PKR and integrated stress response (ISR) were pharmacologically modulated using C16 (PKR inhibitor) and ISRIB (eIF2B activator), at non-toxic doses defined by MTT assay. Intracellular HBV DNA was measured by Southern blot, HBV pgRNA and subgenomic RNAs by Northern blot and RT-qPCR, and secreted HBsAg/HBeAg by ELISA. PKR–eIF2α–ATF4 signaling was evaluated by Western blot.Resultsnc886 and PKR were efficiently and specifically knocked down without affecting cell viability. nc886 silencing in Huh7–HBV cells increased PKR-dependent eIF2α phosphorylation and ATF4, reduced HBV pgRNA and subgenomic RNAs, and decreased intracellular HBV DNA and secreted HBsAg/HBeAg. PKR knockdown alone slightly enhanced HBV readouts and completely rescued nc886-mediated inhibition of HBV replication and ISR activation in dual-knockdown cells. C16 or ISRIB restored HBV DNA, RNA and antigen production in nc886-silenced or Poly(I:C)-treated cells, while having no effect in control cells, indicating that rescue depended on ISR modulation.Conclusionnc886 acts as a critical negative regulator of PKR-dependent ISR signaling during HBV replication in Huh7 cells. Its depletion activates PKR and eIF2α, imposing a translational block that suppresses HBV gene expression. The nc886–PKR–eIF2α module represents a novel host regulatory axis with potential relevance for host-directed HBV therapies.

Background:Current antivirals for orolabial Herpes simplex virus type 1 (HSV-1) often provide incomplete suppression and limited reactivation control, sustaining recurrent oral lesions and inflammation that compromise oral health. HSV-1 subverts host signaling networks to enhance its replication and trigger inflammation. Among these, the extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways are hijacked to facilitate viral gene expression and cell survival. Objectives:In this study, we employed U0126 [a mitogen-activated protein kinase 1/2 (MEK1/2) inhibitor] and LY294002 [a phosphatidylinositol 3-kinase (PI3K) inhibitor] as targeted pharmacological tools to intercept HSV-1's exploitation of host keratinocyte signaling. Methods:Human HaCaT keratinocytes were infected with HSV-1 and treated with U0126 or LY294002. Western blotting was used to assess phosphorylation of ERK1/2 and activation of protein kinase B (AKT). MTT assays were performed to evaluate cell viability. Real-time PCR was utilized to quantify viral transcripts (ICP0, ICP4, gB, and gC) and inflammatory cytokines [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)]. Confocal microscopy was employed to visualize the intracellular distribution of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), phosphorylated activation of protein kinase B (p-AKT), and HSV-1 glycoprotein D (gD). Viral titers were determined using plaque assays. Results:The HSV-1 infection induced a time-dependent increase in phosphorylation of ERK1/2 and AKT, with p-ERK1/2 peaking at 12 h and p-AKT increasing 2.5-fold by 24 h. Cell viability declined from 100% at baseline to 45% at 24-hours post-infection (hpi). Treatment with U0126 and LY294002 reduced p-ERK1/2 and p-AKT levels to 25% and 30% of infected controls, respectively, restoring viability to 82 - 86%. Both inhibitors markedly suppressed viral gene expression (ICP0, ICP4, gB, gC down by 60 - 80%) and inflammatory cytokines (IL-6 and TNF-α reduced by > 50%). Plaque assays showed a strong decline in infectious titers - from 175 plaques per well in untreated infection to 60 and 45 plaques after U0126 and LY294002, respectively. Confocal imaging further revealed diminished nuclear accumulation of p-ERK1/2 and p-AKT, indicating disruption of post-entry signaling critical for viral replication. Conclusions:Targeting host signaling bottlenecks with U0126 and LY294002 offers a dual-pronged antiviral strategy against HSV-1 by dismantling the ERK/AKT axis critical for replication and inflammatory amplification. These findings position MEK1/2 and PI3K as promising therapeutic nodes for managing cutaneous HSV-1 infections. This host-directed dual-pathway inhibition may therefore help reduce recurrent orolabial HSV-1 lesions.

The rapid rise of multidrug-resistant and extensively drug-resistant bacterial infections has renewed interest in bacteriophages as adaptable, targeted antimicrobials. Recent advances in phage engineering, including CRISPR-based approaches, now make it possible to refine host range, strengthen lytic performance, and deliver genetic payloads that target clinically important resistance determinants such as blaNDM, mecA, and mcr-1. In parallel, jumbo phages with large genomes often encode additional functions that support replication and biofilm disruption, offering practical advantages in densely structured infections where antibiotics perform poorly. A second limitation in phage translation has been measurement: in most settings, dosing and treatment duration remain guided by indirect endpoints rather than real-time information on distribution and activity. Near-infrared bioimaging addresses this gap by enabling noninvasive tracking of infection burden and phage kinetics in vivo through bacteriophytochrome-derived reporters, including iRFPs, miRFPs, and PAiRFPs. In this review, we bring these developments together and discuss how CRISPR-enabled phage engineering, jumbo-phage biology, and near-infrared readouts can be integrated into a precision framework that is measurable, adaptable, and clinically interpretable. We examine evidence across major drug-resistant pathogens, including Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Burkholderia cepacia, and Mycobacterium abscessus. We also summarize practical constraints that remain central to clinical translation, manufacturing quality, host immune neutralization, and regulatory variability, and outline a realistic development pathway in which engineered phages and companion diagnostics progress from animal models to carefully defined clinical indications. Together, these advances support a shift from empirical phage use toward a more standardized, data-driven approach to treating drug-resistant infections.

Abstract Hepatitis C virus (HCV) presents a significant global health concern, affecting 3.3% of the world's population. The primary mode of HCV transmission is through blood and blood products. Patients with beta thalassemia, who rely on lifelong blood transfusions, are particularly vulnerable to HCV infections. This study aimed to assess the prevalence of hepatitis C virus infections among multitransfused thalassemic patients in the twin cities of Pakistan's capital. The clinical research, involving the enrollment of 262 multitransfused beta thalassemic patients residing in the capital twin cities of Pakistan. The investigation encompassed the evaluation of hepatitis C virus presence, alanine aminotransferase (ALT) levels, serum creatinine, hepatomegaly, splenomegaly, and the occurrence of splenectomy. The overall prevalence of Hepatitis C virus infections was notably high at 55.73%. This was particularly pronounced among patients aged 20 years and older, with a 100% infection rate. In HCV-positive thalassemic patients, the average ALT level was observed to be 98 U/L, while average creatinine values stood at 0.39 mg/dL. Additionally, hepatomegaly was prevalent in 82.20% of HCV-positive thalassemic patients, featuring an average liver size increase of 4.33 cm. Splenomegaly was evident in 67.12% of HCV-positive thalassemic patients, with an average spleen size augmentation of 4.46 cm. Splenectomy was identified in 15.75% of cases. The incidence of HCV infections in the thalassemic population of Pakistan is alarmingly high. Furthermore, the risk of contracting HCV infections escalates with the advancing age of thalassemic patients. Elevated ALT levels and hepatomegaly were pervasive among the majority of HCV-positive thalassemic patients. Consequently, there is a compelling need for rigorous screening of blood products prior to transfusion to mitigate the future burden of HCV in Pakistan.

Growing pains are a prevalent condition in children, often leading to discomfort and anxiety for both patients and their families. These pains typically manifest as bilateral limb discomfort that occurs primarily in the evenings or at night, affecting approximately 10-20% of the pediatric population. Despite their benign nature, growing pains pose significant challenges in pediatric emergency care due to their episodic nature and lack of specific diagnostic markers. Recent research has shifted the understanding of growing pains from a simplistic view of mere skeletal growth to a multifactorial condition influenced by genetic predisposition, vitamin D deficiency, hypermobility syndrome, and psychosocial factors. This evolving perspective introduces new diagnostic uncertainties as healthcare providers must differentiate growing pains from serious underlying conditions, such as infections, malignancies, and autoimmune disorders. Communication with parents plays a critical role, as they often seek immediate reassurance amid concerns about their child's health. The integration of mental health evaluations and tailored pain management strategies, including non-pharmacological approaches, is essential for effective treatment. Additionally, establishing structured follow-up care can aid in monitoring symptom progression and improving long-term outcomes. In conclusion, addressing growing pains requires a holistic approach that encompasses both physical and psychological aspects of care. By enhancing the understanding of this condition and improving communication and management strategies, pediatric emergency care can better support children experiencing growing pains and their families

Abstract Amidst the ongoing COVID-19 pandemic, the imperative of our time resides in crafting stratagems of utmost precision to confront the relentless SARS-CoV-2 and quell its inexorable proliferation. A paradigm-shifting weapon in this battle lies in the realm of nanoparticles, where the amalgamation of cutting-edge nanochemistry begets a cornucopia of inventive techniques and methodologies designed to thwart the advances of this pernicious pathogen. Nanochemistry, an artful fusion of chemistry and nanoscience, provides a fertile landscape for researchers to craft innovative shields against infection. Within this intricate tapestry, nanoparticles emerge as champions, offering multifaceted solutions encompassing detection, treatment, prevention, and the precise targeting of SARS-CoV-2 incursions. Noteworthy among these innovations, the Silver (Ag) Respi-strips command our attention. These strips stand as exemplars of ingenuity, illuminating the path to swift and precise test detection. Moreover, the integration of Ag-based textile materials into the arsenal against viral propagation opens a promising avenue to curtail the virus's insidious reach. The indomitable force of iron nanoparticles, duly sanctioned by the esteemed FDA, shines as a beacon of hope in the treatment of infection. Their interaction with the glycoprotein spikes of the virus unleashes an inhibitory action of profound consequence. Meanwhile, the domain of diagnostics has been revolutionized by the advent of Magnetic Nanoparticles (MNPs). Their role in automating nucleic acid extraction and purification has proven indispensable, particularly in the diagnostic milieu of SARS-CoV-2. These MNPs wield a magnetic allure, streamlining diagnostic processes with unmatched precision. In this realm of nano-wonders, Gold nanoparticles rise as formidable sentinels, poised at the intersection of versatility and innovation. Their functionalization via a kaleidoscope of functional groups or in concert with antiviral drug combinations augments their prowess. These microscopic champions effectively hinder viral ingress into host cells and orchestrate the controlled release of antiviral agents, casting a profound influence on the course of viral infections. The pandemic landscape has borne witness to the ascendancy of nanotechnology, unveiling an arsenal of nanoparticle-based strategies that promise to defy, detect, treat, and ultimately vanquish SARS-CoV-2. The future beckons, and within the infinitesimal realm of nanoparticles, we find the promise of a brighter, healthier tomorrow.

Abstract Leishmaniasis, caused by the Leishmania parasite, remains a persistent public health challenge in Pakistan. Despite control efforts, the disease prevalence continues to rise, particularly among pediatric populations. Understanding prevalence patterns and transmission dynamics is critical for effective control strategies. This study aims to analyze leishmaniasis prevalence data from January 2016 to July 2023 in Pakistan. Specific objectives include assessing temporal trends, demographic patterns, and geographical hotspots of transmission, while emphasizing the need for enhanced surveillance and research for targeted interventions. Retrospective analysis was conducted on leishmaniasis prevalence data collected from multiple healthcare facilities across Pakistan. Data included results from diagnostic tests on suspected cases, encompassing both pediatric and adult patients. Descriptive statistical analysis was employed to evaluate prevalence rates, demographic characteristics, and geographical distribution of positive cases. Analysis revealed an increasing trend in leishmaniasis prevalence over the study period. Initially, from 2016 to 2020, a positivity rate of 27% was observed exclusively among pediatric patients in Islamabad, with no adult cases. Subsequently, from 2017 to 2022, the positivity rate increased to 42%, affecting both pediatric and adult populations in Islamabad, Rawalpindi, and Swat. Notably, between July 2022 and July 2023, the positivity rate surged to 56%, primarily impacting adult males in the identified hotspots. The study provides evidence of rising leishmaniasis prevalence in Pakistan, particularly among pediatric patients. Identified hotspots suggest localized transmission, warranting targeted interventions. Enhanced surveillance and research efforts are crucial for understanding disease dynamics and implementing effective control measures. Priority should be given to vulnerable populations and high-burden regions to mitigate leishmaniasis impact in Pakistan.

Background:Chronic pulmonary infections pose a significant health burden, with accumulating evidence suggesting their potential to trigger oncogenic transformation. However, the link between chronic bacterial pneumonia and early neoplastic changes remains poorly understood, particularly in juvenile lungs. Objectives:The present study investigates how repeated Pseudomonas aeruginosa infection induces inflammation, oxidative stress, DNA damage, and oncogenic signaling in juvenile mice, and explores potential pharmacological targets to prevent long-term oncogenic consequences. Methods:Juvenile BALB/c mice received intranasal challenges with P. aeruginosa on days 0, 5, and 10. Lung tissues were collected at baseline (day 0) and after the establishment of chronic infection (day 21) for all downstream analyses. Lung tissues were analyzed for inflammatory [factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α)], oxidative [nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1)], and DNA damage (γH2AX) markers using Western blotting, quantitative real-time PCR (qPCR), and immunofluorescence microscopy. Cell viability was assessed using MTT assays, and wound healing capacity was evaluated through scratch assays. Oncogenic markers (Myc, Kras) were quantified by qPCR. Results:Chronic P. aeruginosa infection led to persistent upregulation of inflammatory proteins (NF-κB, COX-2, TNF-α) and oxidative stress markers (Nrf2, HO-1) in lung tissues on day 21 compared to day 0. Increased γH2AX expression indicated DNA damage, although no significant DNA fragmentation was detected, suggesting sublethal, localized damage. Functionally, chronic infection resulted in a 35% reduction in cell viability and significantly delayed wound healing (60% closure compared to 90% in controls). Importantly, infected tissues displayed a 2.8-fold increase in Myc and a 2.5-fold increase in Kras mRNA levels, indicating early oncogenic signaling. Conclusions:Chronic P. aeruginosa infection in juvenile mice induces a sustained inflammatory and oxidative response, leading to epithelial cell dysfunction and activation of oncogenic pathways. These findings highlight the need for early therapeutic intervention targeting inflammation and oxidative stress to mitigate malignant transformation risks associated with recurrent pediatric lung infections. Agents modulating NF-κB activity or enhancing antioxidant defenses, such as Nrf2 activators, may represent promising pharmacological strategies. Early intervention and monitoring of chronic lung infections in pediatric populations are essential to mitigate potential oncogenic risks.

Chronic Hepatitis B Virus (HBV) infection remains a formidable global health challenge, driving severe liver complications such as hepatocellular carcinoma (HCC) and pyogenic liver abscesses (PLA). At the core of HBV persistence lies covalently closed circular DNA (cccDNA), a viral reservoir that fuels ongoing infection despite antiviral treatments. This review highlights molecular mechanisms governing cccDNA formation, maintenance, and clearance, spotlighting innovative therapeutic strategies to disrupt this key viral element. We explore cutting-edge approaches, including epigenetic modulation to silence cccDNA, RNA interference (RNAi) for viral RNA degradation, and CRISPR/Cas genome editing to excise cccDNA directly. Additionally, emerging antiviral therapies and immunotherapies, such as therapeutic vaccines and immune checkpoint inhibitors, offer new avenues for enhanced treatment efficacy. Special attention is given to the clinical complexities of managing HBV in patients with co-morbid conditions like HCC and PLA, emphasizing the necessity of a multidisciplinary approach. The interplay between antibacterial and antiviral therapies in PLA-associated HBV cases is critically examined to prevent treatment antagonism, ensuring optimal patient outcomes. Advanced therapeutic strategies, including nucleos(t)ide analogs, interferon therapy, and novel genomic interventions, are explored in both isolated HBV infection and PLA co-infections. Personalized regimens remain pivotal in enhancing therapeutic efficacy and long-term disease control. Current review advocates for a shift toward precision medicine, highlighting the critical need for interdisciplinary collaboration to bridge molecular discoveries with clinical innovations. Ultimately, these advancements promise to revolutionize the management of chronic HBV, paving the way for potential cures and improved patient outcomes.

Background Kidney failure with replacement therapy (KFRT) such as dialysis or transplantation represents a severe stage of chronic kidney disease (CKD) and poses a major global health burden. Although many CKD cases are diagnosed in the earlier stages, the greatest risk occurs when CKD progresses to KFRT. Despite its considerable financial and imposing impact on public health, there is a notable gap in international policies addressing CKD and KFRT. To bridge this gap and help policy makers and health systems effectively tackle the public health challenge of KFRT, a better understanding of the disease burden is essential. Thus, this analysis aims to provide a detailed overview of the global prevalence of KFRT and its associated aetiologies with estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) from 1990 to 2023. Methods This study defined KFRT as individuals on maintenance dialysis for 90 days or more or those who have undergone a kidney transplant, aligning with the Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Renal registries served as the primary data sources. Prevalence and underlying aetiology estimates (type 1 diabetes, type 2 diabetes, hypertension, glomerulonephritis, and other causes) were generated with DisMod-MR 2.1, an epidemiological Bayesian mixed-effects meta-regression modelling tool. Both all-age and age-standardised estimates were reported and accompanied with 95% uncertainty intervals (UIs). Findings In 2023, the number of global cases of KFRT was 4 center dot 59 million (95% UI 4 center dot 17-5 center dot 08) for both sexes and all ages, with an age-standardised prevalence of 50 center dot 7 (46 center dot 1-56 center dot 0) per 100 000 population. Over the past three decades, there has been a steady increase in KFRT prevalence globally. The highest prevalence was found in the GBD high-income regions, while the lowest was observed in sub-Saharan Africa. KFRT prevalence was generally higher in countries classified within the World Bank's high-income and upper-middle-income groups, while lower prevalence was more common in countries within the World Bank's low-income and lower-middle-income groups. Additionally, a pronounced sex disparity was identified, where male dialysis and transplant prevalence estimates were consistently higher than those for females in most countries. Type 2 diabetes and hypertension were among the leading associated aetiologies of KFRT globally. From 1990 to 2023, the all-age and age-standardised prevalence estimates across the ascribed aetiologies increased for KFRT, with the largest increases associated with type 2 diabetes and hypertension. Interpretation KFRT affects approximately 5 million people globally, with high treatment and mortality costs. Our study unveiled considerable geographical variation in KFRT prevalence, which should be seen as indicators of healthcare system opportunities. As the prevalence of the leading aetiologies of KFRT-type 2 diabetes and hypertension-continues to rise, there is a crucial need to prioritise the development and implementation of cost-effective strategies aimed at preventing CKD and its progression to KFRT, particularly in low-resource settings. These preventive efforts must happen in tandem with efforts to expand capacity for dialysis and transplant services. Copyright (c) 2025 The Author(s). Published by Elsevier Ltd.