Liver cirrhosis is a complication usually due to the consequence of persistent chronic liver disease. It is associated with different mechanisms, including hypoalbuminemia, impaired amino acid turnover, and micronutrient deficiencies. Consequently, cirrhotic patients can develop progressive complications like ascites, hepatic encephalopathy, and hepatocellular carcinoma. The liver is a vital organ that regulates the different metabolic pathways and transportation of trace elements. Zn is an indispensable micronutrient trace element involved in its crucial functions in cellular metabolic activity. Zn mediates its action by binding to a wide range of proteins; therefore, it imparts numerous biological effects, including cellular division, differentiation, and growth. It is also involved in critical processes for the biosynthesis of structural proteins and regulation of transcription factors and acts as a co-factor for the various enzymatic processes. As the liver is a significant regulator of Zn metabolism, its abnormalities lead to Zn deficiency, which has consequences on cellular, endocrine, immune, sensory, and skin dysfunctions. Conversely, Zn deficiency may modify the functions of hepatocytes and immune responses (acute phase protein production) in inflammatory liver diseases. This review has concisely stated the evolving indication of the critical role of Zn in biological processes and complications associated with liver cirrhosis pathogenesis due to Zn deficiency.

Plasmid-mediated colistin resistance (Col-R) conferred by mcr genes endangers the last therapeutic option for multifarious β-lactamase-producing bacteria. The current study aimed to explore the mcr gene molecular epidemiology in extensively drug-resistant (XDR) bacteria. Col-R gram-negative bacterial strains were screened using a minimum inhibitory concentration (MIC) breakpoint ≥4 µg/mL. Resistant isolates were examined for mcr variants, extended-spectrum β-lactamase, AmpC, and carbapenemase genes using polymerase chain reaction (PCR). The MIC breakpoints for mcr-positive strains were determined using broth microdilution and E-test strips. Overall, 19/718 (2.6%) gram-negative rods (GNRs) harboring mcr were identified, particularly in pus (p = 0.01) and tracheal secretions (p = 0.03). Molecular epidemiology data confirmed 18/19 (95%) mcr-1 and 1/19 (5%) mcr-2 genes. Integron detection revealed 15/17 (88%) Int-1 and 2/17 (12%) Int-2. Common co-expressing drug-resistant β-lactamase genes included 8/16 (50%) bla_CTM-1, 3/16 (19%) bla_CTM-15, 3/3 (100%) bla_CMY-2, 2/8 (25%) bla_NDM-1, and 2/8 (25%) bla_NDM-5. The MIC₅₀ and MIC₉₀ values (µg/mL) were as follows: Escherichia coli, 12 and 24; Klebsiella pneumoniae, 12 and 32; Acinetobacter baumannii, 8 and 12; and Pseudomonas aeruginosa, 32 and 64, respectively. Treatment of XDR strains has become challenging owing to the co-expression of mcr-1, mcr-2, multifarious β-lactamase genes, and integrons.

Background: The therapeutic management of carbapenem-resistant Acinetobacter baumannii (CR-AB) represents a serious challenge to the public health sector because these pathogens are resistant to a wide range of antibiotics, resulting in limited treatment options. The present study was planned to investigate the clonal spread of CR-AB in a clinical setting. Methodology: A total of 174 A. baumannii clinical isolates were collected from a tertiary care hospitals in Lahore, Pakistan. The isolates were confirmed by VITEK 2 compact system and molecular identification of recA and bla_OXA-51. Antimicrobial profile and the screening of carbapenem-resistant genes were carried out using VITEK 2 system and PCR, respectively. The molecular typing of the isolates was performed according to the Pasteur scheme. Results: Of the 174 A. baumannii isolates collected, the majority were isolated from sputum samples (46.5%) and in the intensive care unit (ICU, 75%). Among these, 113/174 (64.9%) were identified as CR-AB, and 49.5% and 24.7% harbored bla_OXA-23 and bla_NDM-1, respectively. A total of 11 (9.7%) isolates co-harbored bla_OXA-51, bla_NDM-1, and bla_OXA-23. Interestingly, 46.9% of the CR-AB belonged to sequence type 2 (ST2; CC1), whereas 15.9% belonged to ST1 (CC1). All of the CR-AB isolates showed extensive resistance to clinically relevant antibiotics, except colistin. Conclusion: The study concluded CR-AB ST2 clone harboring bla_OXA-23 and bla_NDM-1 are widely distributed in Pakistan’s clinical settings, which could result in increased mortality. Strict compliance with the National Action Plan on Antimicrobial Resistance is necessary to reduce the impacts of these strains.

Macrophages are one of the first innate defense barriers and play an indispensable role in communication between innate and adaptive immune responses, leading to restricted Mycobacterium tuberculosis (Mtb) infection. The macrophages can undergo programmed cell death (apoptosis), which is a crucial step to limit the intracellular growth of bacilli by liberating them into extracellular milieu in the form of apoptotic bodies. These bodies can be taken up by the macrophages for the further degradation of bacilli or by the dendritic cells, thereby leading to the activation of T lymphocytes. However, Mtb has the ability to interplay with complex signaling networks to subvert macrophage apoptosis. Here, we describe the intelligent strategies of Mtb inhibition of macrophages apoptosis. This review provides a platform for the future study of unrevealed Mtb anti-apoptotic mechanisms and the design of therapeutic interventions.

The novel dual PI3K/mTOR inhibitor NVP-BGT226 displays cytotoxic activity in both normoxic and hypoxic hepatocarcinoma cells The novel dual PI3K/mTOR inhibitor NVP-BGT226 displays cytotoxic activity in both normoxic and hypoxic hepatocarcinoma cells

Parkinson's disease (PD) remains one of the most formidable challenges in central nervous system (CNS) drug delivery due to the restrictive blood–brain barrier (BBB) and limited efficacy of current dopaminergic therapies. Lipid-based nanocarriers, including liposomes, cubosomes, and nanostructured lipid carriers, have emerged as versatile nose-to-brain platforms offering rapid CNS access, dual encapsulation of synthetic and plant-derived neuroprotective agents, and tunable release kinetics. This review bridges nanoscale material design (e.g., lipid crystallinity, phase transitions, hybridization with plant exosomes) with intranasal transport pathways and therapeutic outcomes in PD. We highlight multifunctional innovations such as stimuli-responsive lipid systems, exosome–cubosome hybrids, and AI-guided formulation modeling coupled with microfluidic manufacturing. By linking mechanistic insights with translational hurdles—including safety and regulatory challenges—we provide a forward-looking roadmap for next-generation nanotherapies poised to redefine PD management and accelerate clinical translation.