Among all available antimicrobials, antibiotics hold a prime position in the treatment of infectious diseases. However, the emergence of antimicrobial resistance (AMR) has posed a serious threat to the effectiveness of antibiotics, resulting in increased morbidity, mortality, and escalation in healthcare costs causing a global health crisis. The overuse and misuse of antibiotics in global healthcare setups have accelerated the development and spread of AMR, leading to the emergence of multidrug-resistant (MDR) pathogens, which further limits treatment options. This creates a critical need to explore alternative approaches to combat bacterial infections. Phytochemicals have gained attention as a potential source of alternative medicine to address the challenge of AMR. Phytochemicals are structurally and functionally diverse and have multitarget antimicrobial effects, disrupting essential cellular activities. Given the promising results of plant-based antimicrobials, coupled with the slow discovery of novel antibiotics, it has become highly imperative to explore the vast repository of phytocompounds to overcome the looming catastrophe of AMR. This review summarizes the emergence of AMR towards existing antibiotics and potent phytochemicals having antimicrobial activities, along with a comprehensive overview of 123 Himalayan medicinal plants reported to possess antimicrobial phytocompounds, thus compiling the existing information that will help researchers in the exploration of phytochemicals to combat AMR.

CD8⁺ T cells play basic roles in the immune system in a tumor microenvironment (TME) to fight cancer. Several reports have suggested signs of the involvement of tumor protein p53 (TP53) in a complex immune system network. Moreover, our previous research indicated that TP53 orchestrates the polarization and infiltration of macrophages into the TME. In the present study, the clinical function of TP53 status (wild/mutant) in CD8⁺ T cell infiltration was assessed using more than 10,000 The Cancer Genome Atlas (TCGA) samples from 30 cancer types through Tumor Immune Estimation (TIMER). Our investigation revealed that CD8⁺ T cell infiltration was higher in head and neck squamous cell carcinoma (HNSC) and uterine corpus endometrial carcinoma (UCEC) patients with wild-type TP53 than in those with mutant TP53. Wild-type TP53 conferred a good prognosis for HNSC and UCEC (P<0.05). In contrast, CD8⁺ T cell infiltration in lung adenocarcinoma (LUAD) patients with wild-type TP53 was much lower than in those with mutant TP53. Notably, clinical outcomes for LUAD with wild-type TP53 were poor (P<0.05). This study was the first to provide insights into the novel association of TP53 with CD8⁺ T cells infiltration in the TME in patients with HNSC, LUAD, and UCEC. Therefore, TP53 status acts as a prognostic marker, and this can be used as a basis to further study the effect of targeting TP53 in these patients. Furthermore, our study found that TP53 status was a reliable predictive factor and therapeutic target in patients with HNSC and UCEC.

Background: CDKN2A (p16^INK4a^) is integral to the regulation of the RB–E2F cell-cycle checkpoint and is widely acknowledged as a surrogate marker for high-risk human papillomavirus (HPV)-related cervical neoplasia. Nevertheless, its diagnostic and prognostic significance in uterine corpus endometrial carcinoma (UCEC), a predominantly HPV-independent malignancy, remains inadequately characterized. This study utilized an integrated multi-omics approach to examine CDKN2A dysregulation in cervical squamous cell carcinoma (CESC) and UCEC. Methods: Pan-cancer and tumor–normal differential expression analyses were performed using TIMER2.0 and GEPIA2 (TCGA/GTEx). Clinicopathological correlations were assessed with UALCAN. Protein expression patterns were analyzed using immunohistochemistry data from the Human Protein Atlas (HPA). Prognostic significance and immune-infiltration associations were evaluated using TCGA survival data and TIMER modules. Independent transcriptomic validation and diagnostic classification performance were assessed using GEO datasets GSE9750 (CESC) and GSE63678 (UCEC), including ROC-AUC analysis with cross-validation. Results: Integrated analyses revealed elevated CDKN2A expression in both CESC and UCEC across multiple transcriptomic cohorts, with pronounced tumor-specific protein expression on immunohistochemistry. TCGA-only tumor–normal RNA comparisons were non-significant, likely due to limited normal sample representation. In independent GEO cohorts, CDKN2A exhibited excellent tumor–normal discrimination in CESC (AUC = 0.982) and moderate discrimination in UCEC (AUC = 0.761). Survival analysis indicated tumor-specific patterns, with limited prognostic stratification in CESC and context-dependent associations in UCEC. Immune-infiltration analysis suggested tumor-type-specific interactions between CDKN2A expression and immune cell subsets. Conclusions: CDKN2A exhibits strong diagnostic performance in HPV-associated cervical cancer and moderate, cohort-dependent discriminatory ability in endometrial carcinoma. These findings reinforce its established diagnostic role in CESC and propose adjunctive utility in UCEC, underscoring the importance of tumor-contextual interpretation of CDKN2A expression in gynecologic malignancies.

The gold-standard approach for diagnosing and confirming Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) infection is reverse transcription-polymerase chain reaction (RT-PCR). This method, however, is inefficient in detecting previous or dormant viral infections. The presence of antigen-specific antibodies is the fingerprint and cardinal sign for diagnosis and determination of exposure to infectious agents including Corona virus disease-2019 (COVID-19). This cross-sectional study examined the presence of SARS-CoV-2 spike-specific immunoglobulin G (IgG) among asymptomatic blood donors in Makkah region. A total of 4368 asymptomatic blood donors were enrolled. They were screened for spike-specific IgG using ELISA and COVID-19 RNA by real-time PCR. COVID-19 IgG was detected among 2248 subjects (51.5%) while COVID-19-RNA was detected among 473 (10.8%) subjects. The IgG frequency was significantly higher among males and non-Saudi residents (p < 0.001 each) with no significant variation in IgG positivity among blood donors with different blood groups. In addition, COVID-19 RNA frequency was significantly higher among donors below 40-years old (p = 0.047, χ² = 3.95), and non-Saudi residents (p = 0.001, χ² = 304.5). The COVID-19 IgG levels were significantly higher among the RNA-positive donors (p = 001), and non-Saudi residents (p = 0.041), with no variations with age or blood group (p > 0.05). This study reveals a very high prevalence of COVID-19 IgG and RNA among asymptomatic blood donors in Makkah, Saudi Arabia indicating a high exposure rate of the general population to COVID-19; particularly foreign residents. It sheds light on the spread on COVID-19 among apparently healthy individuals at the beginning of the pandemic and could help in designing various control measures to minimize viral spread.

Annexin A2 (ANXA2) is involved in cell-surface fibrinolysis and has been associated with hepatocellular carcinoma (HCC). We examined ANXA2 expression in HCC and its associations with survival and immune–hemostatic gene expression. ANXA2 transcript expression was assessed in The Cancer Genome Atlas liver cancer cohort (TCGA-LIHC) and an independent HCC dataset (GSE25097). Public protein datasets were used to examine ANXA2 abundance. We analyzed clinicopathological associations, overall survival, tumor–normal tissue discrimination, and correlations with selected immune, coagulation, fibrinolytic, and inflammatory genes. ANXA2 expression was higher in HCC than in non-tumor liver tissue in the transcriptomic analyses and was elevated in the protein analyses. Higher ANXA2 expression was associated with poorer overall survival after adjustment for age, sex, and pathological stage (hazard ratio, 1.26; 95% confidence interval, 1.07–1.49; p = 0.006). Within TCGA-LIHC, ANXA2 expression discriminated tumor from normal tissue (area under the curve, 0.895; 95% confidence interval, 0.852–0.933); this performance was not independently validated. ANXA2 expression also correlated with selected fibrinolytic, inflammatory, and immune-related genes. GSE25097 supported the differential-expression finding. ANXA2 is overexpressed in HCC and is associated with poorer survival and an immune–hemostatic transcriptional pattern. The correlations do not establish that ANXA2 regulates these processes.