Extensively drug-resistant tuberculosis (XDR-TB) remains a critical global health threat, largely due to the toxicity, prolonged treatment durations, and severe dysbiosis associated with conventional broad-spectrum antibiotic regimens. To address this, we evaluated the in vitro and in vivo efficacy of CRISPR-Cas therapeutics targeting key XDR-TB resistance mutations, deploying distinct modalities including double-strand break (DSB) nucleases (Cas9, Cas12a) for targeted bacterial killing and base editors (CBE/ABE) for resistance allele correction, delivered via lipid nanoparticles (LNPs) or engineered bacteriophages (BxP-1). In vitro, DSB-targeting Cas9 and Cas12a achieved high bactericidal activity against rpoB (S450L) and katG (S315T) mutants, yielding 99.2% and 98.5% kill rates, respectively, while multiplexed Cas9 targeting both loci achieved near-complete clearance (99.9% kill). Conversely, base editors targeting gyrA (D94G) and rrs (A1401G) resensitized resistant strains without direct killing, successfully restoring moxifloxacin and amikacin MICs to 0.25 μg/mL and 1.0 μg/mL. In vivo, the multiplexed rpoB + katG Cas9 therapy demonstrated the highest efficacy with a 3.5 ± 0.2 Δ log₁₀ CFU reduction in lung burden, outperforming the standard XDR-TB small-molecule regimen (3.1 ± 0.3 Δ log₁₀ CFU), with single target DSB and base-editing therapies also yielding substantial reductions (1.4–2.8 Δ log₁₀ CFU). Crucially, all CRISPR-Cas modalities exhibited exceptional microbiome preservation, with Microbiome Sparing Indices ranging from 0.92 to 0.98, compared to a significantly depleted index of 0.45 for the standard antibiotic regimen. Ultimately, these findings demonstrate that CRISPR-Cas therapeutics, particularly multiplexed DSB approaches and targeted base editors, provide highly effective, mutation-specific clearance and resensitization of XDR-TB, representing a promising next-generation paradigm for treating drug-resistant tuberculosis with minimized host collateral damage.
Dysglycemia may alter host susceptibility to urinary infection, while the diagnostic performance of urinalysis varies across clinical populations. This manuscript describes the pattern of glycemic-group labels, urine-culture results, and selected urinalysis findings in a supplied summary of 100 records reportedly involving adults with suspected urinary tract infection. The summary recorded 52 culture-positive results (52.0%). Culture positivity ranged from 43.2% in the no-known diabetes/below-threshold group to 62.5% in the diabetes-range screen-positive group, which contained only eight records. In the comparison based on previously diagnosed diabetes, culture positivity was 56.7% among records with known diabetes and 50.0% among records without known diabetes (crude odds ratio 1.31, 95% CI 0.55-3.09; p=0.541). Pyuria of at least 10 white blood cells per high-power field was recorded in 53.0% of records, leukocyte esterase was non-negative in 64.0%, nitrite was positive in 37.0%, and urine glucose was trace or higher in 21.0%.
Introduction: Surgical removal of impacted mandibular third molars is commonly associated with significant postoperative pain, which can affect patient recovery and comfort. Local administration of dexamethasone may reduce inflammation and pain, improving postoperative outcomes without additional invasive interventions. Material and Methods: A randomized clinical trial (NCT07538375) was conducted at the Department of Oral and Maxillofacial Surgery, 28 Military Dental Centre, Lahore, Pakistan, from October 2025 to March 2026. A total of 144 patients aged 20–40 years were randomly assigned into two groups (n = 72). Group A received an inferior alveolar nerve block with 2% lignocaine and epinephrine, while Group B received the same block plus 1 ml (8 mg) dexamethasone locally at the surgical site. Pain intensity was measured using VAS at baseline, 24, 48, 72 hours, and day seven. Analgesic consumption was recorded, and data were analyzed with SPSS version 23. Results: The preoperative parameters did not change significantly (p > 0.05) between the two groups, with an average subject age of 38.47 ± 9.86. The group that received dexamethasone required fewer total analgesics within the first 24 hours after surgery (p < 0.001) and had significantly reduced pain levels at 24, 48, 72, and 7 days postoperatively (p < 0.001). The total amount of analgesic medicine utilized at any other time point did not differ significantly (p > 0.05). Conclusions: Administering dexamethasone during the intraoperative phase is an efficient way to manage postoperative pain without the need for invasive treatments.
Background: Primary dysmenorrhea is a common cause of menstrual pain among women of reproductive age and is primarily associated with increased prostaglandin-mediated uterine contractions. Erigeron canadensis L. has traditionally been used in homeopathic practice for painful menstruation, but clinical evidence and information regarding its possible molecular targets remain limited. This pilot study aimed to explore the potential interaction between E. canadensis phytoconstituents and cyclooxygenase-2 (COX-2) using molecular docking and to evaluate changes in pain intensity following administration of E. canadensis mother tincture in women with primary dysmenorrhea. Methods: The study comprised two components: an in silico molecular docking study and a prospective clinical pilot study. Phytoconstituents of E. canadensis were docked against COX-2 using the Schrödinger Glide platform, and docking scores were evaluated. The clinical component was conducted at Yenepoya Homoeopathic Medical College & Hospital from May to July 2026. Thirteen women aged 18–35 years with clinically diagnosed primary dysmenorrhea, a Visual Analogue Scale (VAS) pain score ≥4, and symptom characteristics corresponding to E. canadensis were enrolled consecutively. Participants received E. canadensis mother tincture (Q) during episodes of menstrual pain and were followed for two consecutive days. Pain intensity was assessed using the VAS at baseline, first follow-up, and second follow-up. Changes in VAS scores were analysed using the Friedman test, followed by Bonferroni-adjusted Wilcoxon signed-rank tests when appropriate. Kendall's coefficient of concordance (W) was used to estimate effect size. Results: Seven E. canadensis phytoconstituents showed favorable predicted interactions with COX-2, with reported docking scores ranging from 120.123 to 127.746. In the clinical study, the median VAS score decreased from 8.0 (IQR 6.5–8.0) at baseline to 4.0 (IQR 2.0–6.0) at the first follow-up and 0.0 (IQR 0.0–4.5) at the second follow-up. The Friedman test demonstrated a statistically significant difference in VAS scores across the three assessment points (χ²(2) = 12.19, P = 0.002), with a Kendall's W of 0.469, indicating a moderate effect. Conclusion: In this small, uncontrolled pilot study, administration of E. canadensis mother tincture was associated with a significant reduction in menstrual pain over the two-day follow-up period. Molecular docking identified favorable predicted interactions between selected E. canadensis phytoconstituents and COX-2, providing a hypothesis regarding a possible pharmacological pathway. However, docking predictions cannot establish biological activity, and the uncontrolled clinical design precludes causal inference. Larger controlled clinical studies, together with experimental validation of the predicted molecular interactions, are warranted.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β aggregation, tau hyperphosphorylation, oxidative stress, and chronic neuroinflammation. Current pharmacotherapies provide only symptomatic relief and are often associated with adverse effects, necessitating safer multi-target therapeutic strategies. This study aimed to investigate the anti-Alzheimer potential of Ocimum sanctum phytocompounds using an integrated in-silico approach involving molecular docking, ADMET profiling, toxicity prediction, and network pharmacology. Fourteen ligands, including ten phytochemicals and four standard drugs, were evaluated using SwissADME, pkCSM, and StopTox. Network pharmacology identified 64 overlapping targets between phytocompounds and AD-associated genes, with SRC, PTGS2, ESR1, MAPK3, and GSK3B emerging as key hub proteins. Molecular docking analysis revealed strong binding affinities of several phytoconstituents toward these targets. Ursolic acid demonstrated the highest multi-target potential, particularly against PTGS2 (−10.8 kcal/mol) and SRC (−9.8 kcal/mol), outperforming reference drugs in certain interactions. ADMET predictions indicated favorable pharmacokinetic properties for most compounds, with acceptable absorption and blood–brain barrier permeability, while toxicity profiling suggested a generally safe therapeutic window for selected candidates. Collectively, the findings highlight O. sanctum phytochemicals, especially ursolic acid, as promising multi-target modulators against AD pathology, warranting further in vitro and in vivo validation.
