Exploring the Potent Combination of Quercetin-Boronic Acid, Epalrestat, and Urea Containing Nanoethosomal Keratolytic Gel for the Treatment of Diabetic Neuropathic Pain: In Vitro and In Vivo Studies.

Transdermal penetration of therapeutic moieties from topical dosage forms always remains a challenge due to the presence of permeation impeding keratin which should be addressed. The purpose of the study was to formulate quercetin and 4-formyl phenyl boronic acid (QB complex) used for the preparation of nanoethosomal keratolytic gel (EF3-G). The QB complex was confirmed by Fourier transform infrared spectroscopy while skin permeation, viscosity, and epalrestat entrapment efficiency were used for the optimization of nanoethosomal gel. The keratolytic effect of the proposed nanoethosomal gel with urea (QB + EPL + U) was calculated in rat and snake skin. The spherical shape of nanoethosomes was confirmed by scanning electron microscopy. According to the findings of stability studies, viscosity decreases as temperature increases, proving their thermal stability. The negative charge of optimized EF3 with 0.7 PDI proved narrow particle size distribution with homogeneity. Optimized EF3 showed two folds increase of epalrestat permeation in highly keratinized snake skin as compared to rats' skin after 24 h. Antioxidant behaviors of EF3 (QB) > QB complex > quercetin > ascorbic acid proved reduction of oxidative stress in DPPH reduction analysis. Interestingly, the hot plate and cold allodynia test in the diabetic neuropathic rat model reduced 3-fold pain as compared to the diabetic control group which was further confirmed by in vivo biochemical studies even after the eight week. Conclusively, ureal keratolysis, primary dermal irritation index reduction, and improved loading of epalrestat render the nanoethosomal gel (EF3-G) ideal for the treatment of diabetic neuropathic pain.

Safety of glucose-6 phosphate dehydrogenase deficient donors in living right lobe liver donation.

BACKGROUND: The literature lacks data on World Health Organization (WHO) class II and III deficient liver donors who underwent right hepatectomy during living donor liver transplantation (LDLT). METHODS: In this prospective cohort study, we compared the perioperative outcomes of 15 glucose-6 phosphate dehydrogenase (G6PD) deficient living liver donors with a matched cohort of 39 nondeficient living liver donors undergoing right lobe donation. RESULTS: Out of 15 G6PD deficient donors, four (26.67%) donors had class II, and 11 (73.34%) had class III G6PD deficiency. The mean postoperative trough hemoglobin level was significantly lower in the deficient group than the nondeficient group (9.38 ± 1.59 g/dL vs. 10.27 ± .91 g/dL, p = .046). The mean peak indirect bilirubin level was significantly higher in the deficient group than the nondeficient group (2.22 ± 1.38 mg/dL vs. 1.40 ± .89 mg/dL, p = .047), and a similar trend was observed in total serum bilirubin (3.99 ± 2.57 mg/dL vs. 2.99 ± 1.46 mg/dL, p = .038). Biochemical evidence of hemolysis was found only in three (20%) deficient donors, but none of them needed a blood transfusion. No mortality was observed in either group. All other parameters, including demographics, operative parameters, graft characteristics, and hospital stay were comparable between both groups (p > .05). CONCLUSION: G6PD deficiency with WHO class II and above should not be considered a contraindication for right lobe donation.

Evaluation of in vitro antioxidant capacity and reducing potential of polyherbal Coded capsules Arthitec 1 and Arthitec 2.

Free radicals are partially reduced form of metabolites of Nitrogen and Oxygen. These are highly reactive and potentially toxic compounds which are contributing factors in different chronic disease. The present study was aimed to determine antioxidant capability and reducing ability of coded polyherbal capsules (Arthitec 1 & Arthitec 2). DPPH (2,2'-diphenyl-1-picryl hydrazyl) assay is most commonly used method for gauging antioxidant capability of natural compounds. In this assay DPPH act as stable free radical which react with an antioxidant. For measuring reducing ability suspected antioxidant react with ferric tripyridyltriazine (Fe3± TPTZ) complex and convert ferric into ferrous. Results are evident that both capsule formulations Arthitec 1 & Arthitec 2 have promising antioxidant activity and reducing potential. Antioxidant potential of both coded capsules with varied concentrations (10, 50 and 100 µg/ml) were compared and in both cases scavenging activity and as well as reducing ability raised in a dose dependent manner just like standard Butylated hydroxyanisole (BHA).

Appraisal of anti-arthritic and nephroprotective potential of Cuscuta reflexa.

CONTEXT: Cuscuta reflexa Roxb. (Cuscutaceae) has been used traditionally for treating sore knees and kidney problems, but its efficacy has not been scientifically examined in treating arthritis and nephrotoxicity. OBJECTIVE: Present study determines antiarthritic and nephroprotective potential of the aqueous methanolic extract of Cuscuta reflexa (AMECR). MATERIALS AND METHODS: Antiarthritic activity of Cuscuta reflexa in formaldehyde and turpentine oil-induced rat arthritis models was appraised at 200, 400 and 600 mg/kg doses for 10 days and 6 h period, respectively, and in vitro protein denaturation (bovine serum albumin, egg albumin) inhibition was studied at 25-800 µg/mL concentration. The nephroprotective effect involved gentamicin-induced nephrotoxicity in rats at 200, 400 and 600 mg/kg doses. RESULTS: Plant extract at 600 mg/kg significantly reduced paw oedema and joint swelling with maximal inhibition of 71.22% at the 6th hour for turpentine oil and 76.74% on 10th day for formaldehyde. Likewise, in vitro results corroborated significant concentration-dependent increase in percentage protection at 800 µg/mL against both bovine serum albumin (89.30%) and egg albumin (93.51%) denaturation. Similarly, 600 mg/kg dose showed maximum nephroprotection by reducing serum urea (41.400 ± 0.510 mg/dL), uric acid (0.740 ± 0.032 mg/dL), blood urea nitrogen (18.370 ± 0.328), creatinine (3.267 ± 0.076) and minimizing kidney weight gain (0.586 ± 0.005) and histopathological alterations on 8th day. Furthermore, phytochemical and HPLC analysis revealed the presence of important phytoconstituents. DISCUSSION AND CONCLUSIONS: These results suggest that AMECR provides protection against arthritis and nephrotoxicity that might be due to the existence of phytoconstituents, thus supporting folkloric claim.

Diagnostic accuracy of tests for tuberculous pericarditis: A network meta-analysis.

Tuberculous pericarditis (TBP) is a relatively uncommon but potentially fatal extrapulmonary manifestation of tuberculosis. Despite its severity, there is no universally accepted gold standard diagnostic test for TBP currently. The objective of this study is to compare the diagnostic accuracy of the most commonly used tests in terms of specificity, sensitivity, negative predictive value (NPV), and positive predictive value (PPV), and provide a summary of their diagnostic accuracies. A comprehensive literature review was performed using Scopus, MEDLINE, and Cochrane central register of controlled trials, encompassing studies published from start to April 2022. Studies that compared Interferon Gamma Release Assay (IGRA), Xpert MTB/RIF, Adenosine Deaminase levels (ADA), and Smear Microscopy (SM) were included in the analysis. Bayesian random-effects model was used for statistical analysis and mean and standard deviation (SD) with 95% confidence intervals were calculated using the absolute risk (AR) and odds ratio (OR). Rank probability and heterogeneity were determined using risk difference and Cochran Q test, respectively. Sensitivity and specificity were evaluated using true negative, true positive, false positive, and false negative rates. Area under the receiver operating characteristic (AUROC) was calculated for mean and standard error. A total of seven studies comprising 16 arms and 618 patients were included in the analysis. IGRA exhibited the highest mean (SD) sensitivity of 0.934 (0.049), with a high rank probability of 87.5% for being the best diagnostic test, and the AUROC was found to be 94.8 (0.36). On the other hand, SM demonstrated the highest mean (SD) specificity of 0.999 (0.011), with a rank probability of 99.5%, but a leave-one-out analysis excluding SM studies revealed that Xpert MTB/RIF ranked highest for specificity, with a mean (SD) of 0.962 (0.064). The diagnostic tests compared in our study exhibited similar high NPV, while ADA was found to have the lowest PPV among the evaluated methods. Further research, including comparative studies, should be conducted using a standardized cutoff value for both ADA levels and IGRA to mitigate the risk of threshold effect and minimize bias and heterogeneity in data analysis.

A yeast-malic acid crosslinker/polyacrylic acid hydrogel containing doxycycline for the treatment of periodontitis.

Doxycycline (DX) is a drug of choice for the treatment of periodontitis, with the limitation of requiring a high dose, which may be overcome by the preparation of a targeted controlled-release hydrogel containing a newly synthesized yeast-malic acid crosslinker (YMC). YMC was synthesized via thermochemical modification of yeast with malic acid at 100-140 °C and compared with glutaraldehyde-saturated toluene (GST). Swelling capacity, acid and carboxyl content, scanning electron microscopy (SEM) imaging, Brunauer-Emmett-Teller (BET) analysis, viscosity, cross-linking density, DX loading and release behavior at pH 6.5, mucoadhesion, and antimicrobial and periodontal efficacy of the glutaraldehyde hydrogel (HGG) and YMC hydrogel (HGY) were compared. Changes from C-O (1421 cm-1) to C[double bond, length as m-dash]OOR (1702 cm-1) in the infrared spectroscopy, along with changes in the degree of substitution from 0 to 0.39, degree of esterification from 0 to 40 ± 1.5 and COOH content from 129 ± 0.5 to 290 ± 0.5 (meq. per 100 g), were found between yeast to YMC, respectively. The results revealed 1.5 times more dynamic swelling, 0.25-fold decrease in acid content, 2.3-fold increase in carboxyl content, and 1.2- and 2.1-fold increases in cross-linking density and viscosity of HGY as compared to HGG, respectively. The SEM and BET results revealed that HGY had a 2 times greater porous surface than HGG. HGY/DX was 35 ± 2% more effective in controlling periodontitis bacteria, decreased periodontal depth from 4 to 3.2 mm, and gingival index from 3 to 1 as compared to HGG/DX in patients suffering from periodontitis. HGY/DX not only serves as a tool for the controlled release of DX in periodontal pockets but also contributes to the treatment of gingival periodontitis.

Phosphotungstic Acid Clusters Decorated Znln2S4 Nanoflowers as Molecular-Scale S-Scheme Heterojunctions for Simultaneous H2 Evolution and Benzyl Alcohol Upgrading.

Simultaneous utilization of photogenerated electrons and holes to achieve overall redox reactions is attractive but still far from practical application. The emerging step (S)-scheme mechanism has proven to be an ideal approach to inhibit charge recombination and supply photoinduced charges with highest redox potentials. Herein, a hierarchical phosphotungstic acid (H3PW12O40, HPW)@Znln2S4 (ZISW) heterojunction was prepared through one-pot hydrothermal method for simultaneous hydrogen (H2) evolution and benzyl alcohol upgrading. The fabricated HPW-based heterojunctions indicated much enhanced visible-light absorption, promoted photogenerated charge transfer and inhibited charge recombination, owing to hierarchical architecture based on visible-light responsive Znln2S4 microspheres, and S-scheme charge transfer pathway. The S-scheme mechanism was further verified by free-radical trapping electron spin resonance (ESR) spectra. Moreover, the wettability of composite heterojunction was improved by the modification of hydrophilic HPW, contributing to gaining active hydrogen (H+) from water sustainably. The optimal ZISW-30 heterojunction photocatalyst indicated an enhanced hydrogen evolution rate of 27.59 mmol g-1 h-1 in benzyl alcohol (10 vol. %) solution under full-spectrum irradiation, along with highest benzaldehyde production rate is 8.32 mmol g-1 h-1. This work provides a promising guideline for incorporating HPW into S-scheme heterojunctions to achieve efficient overall redox reactions.

Chitosan-coated halloysite nanotube magnetic microspheres for carcinogenic colorectal hemorrhage and liver laceration in albino rats.

Carcinogenic colorectal hemorrhage can cause severe blood loss and longitudinal ulcer, which ultimately become fatal if left untreated. The present study was aimed to formulate targeted release gemcitabine (GC)-containing magnetic microspheres (MM) of halloysite nanotubes (MHMG), chitosan (MCMG), and their combination (MHCMG). The preparation of MM by magnetism was confirmed by vibrating sample magnetometry (VSM), the molecular arrangement of NH2, alumina, and silica groups was studied by X-ray diffraction (XRD) and energy-dispersive spectroscopy (EDS), the hollow spherical nature of the proposed MM was observed by scanning electron microscopy (SEM), functional groups were characterized by Fourier transform infrared (FTIR) spectroscopy and thermochemical modification was studied by thermogravimetric analysis (TGA). In vitro thrombus formation showed a decreasing trend of hemostatic time for MMs in the order of MHMG3 < MCMG3 < MHCMG7, which was confirmed by whole blood clotting kinetics. Interestingly, rat tail amputation and liver laceration showed 3 folds increased clotting efficiency of optimized MHCMG7 compared to that of control. In vivo histopathological studies and cell viability assays confirmed the regeneration of epithelial cells. The negligible systemic toxicity of MHCMG7, more than 90% entrapment of GC and high % release in alkaline medium made the proposed MM an excellent candidate for the control of hemorrhage in colorectal cancer. Conclusively, the healing of muscularis and improved recovery of the colon from granulomas ultimately improved the therapeutic effects of GC-containing MMs. The combination of both HNT and CTS microspheres made them more targeted.

Repurposing of Strychnine as the Potential Inhibitors of Aldo-keto Reductase Family 1 Members B1 and B10: Computational Modeling and Pharmacokinetic Analysis.

AKR1B1 and AKR1B10 are important members of aldo-keto reductase family which plays a significant role in cancer progression by modulating cellular metabolism. These enzymes are involved in various metabolic processes, including the synthesis and metabolism of hormones, detoxification of reactive aldehydes, and the reduction of various endogenous and exogenous compounds. This study aimed to explore the potential of strychnine as an anticancer agent by targeting AKR1B1 and AKR1B10 via drug repurposing approach. To assess the drug-like properties of strychnine, a physiologically based pharmacokinetic (PKPB) model and High Throughput Pharmacokinetics (HTPK) approach were employed. The obtained results fell within the expected range for drug molecules, confirming its suitability for further investigation. Additionally, density functional theory (DFT) studies were conducted to gain insight into the electronic properties contributing to the drug molecule's reactivity. Building upon the promising DFT results, molecular docking analysis using the AutoDock tool was performed to examine the binding interactions between strychnine and the proposed targets, AKR1B1 and AKR1B10. Findings from the molecular docking studies suggested a higher probability of strychnine acting as an inhibitor of AKR1B1 and AKR1B10 with docking scores of - 30.84 and - 29.36 kJ/mol respectively. To validate the stability of the protein-ligand complex, Molecular Dynamic Simulation (MDS) studies were conducted, revealing the formation of a stable complex between the enzymes and strychnine. This comprehensive approach sheds light on the potential effectiveness of strychnine as a treatment for breast, lung, liver, and pancreatic cancers, as well as related malignancies. The novel insights gained from the physiologically based pharmacokinetic modeling, density functional theory, molecular docking, and molecular dynamics simulations collectively support the prospect of strychnine as a promising molecule for anticancer therapy. Further investigations are warranted to validate these findings and explore the therapeutic potential of strychnine in preclinical and clinical settings.

Boosting of Magnetic, Ferroelectric, Energy Storage Efficiency, and Piezoelectric Properties of Zn Intercalated SrBi4Ti4O15-Based Ceramics.

An appropriate amount of Zn-ions are incorporated into the high Curie temperature bismuth layer-structure ferroelectric material to fabricate Sr0.2Na0.4Pr0.4Bi4Ti4O15:xwt%ZnO; (SNPBT:xZn), with x = 0, 0.10, 0.15, and 0.20 ceramic series to investigate the magnetic, ferroelectric, and energy storage efficiency and piezoelectric properties. Pure SNPBT and SNPBT:xZn ceramics have maintained their structure even after the intercalation of Zn-ions at the lattice sites of SNPBT. The addition of ZnO in SNPBT has improved the multifunctional properties of the material at x = 0.15. At room temperature, SNPBT:0.15Zn has shown a high relative density of 96%, exhibited weak ferromagnetic behavior along with a low saturation magnetization (Ms) of 0.028 emu/g with a low coercive field of 306 Oe, a high remnant polarization (Pr) of 9.04 µC/cm2, a recoverable energy density (Wrec) of ~0.5 J/cm3, an energy conversion efficiency (η) of ~41%, a high piezoelectric co-efficient (d33) of 21 pC/N, and an impedance of 1.98 × 107 Ω, which are much improved as compared to pure SBT or pure SNPBT ceramics. Dielectric Constant (ɛr) versus temperature plots present the sharp peak for SNPBT:0.15Zn ceramic at a Curie temperature (TC) ~ 605 °C, confirming the strong ferroelectric nature of the ceramic. Moreover, SNPBT:0.15Zn ceramic has shown strong, piezoelectric, thermally stable behavior, which remains at 76% (16 pC/N) of its initial value even after annealing at 500 °C. The achieved results clearly indicate that SNPBT:0.15Zn ceramic is a promising candidate for future wide-temperature pulse power applications and high-temperature piezoelectric devices.

Chitosan/halloysite nanotubes microcomposites: A double header approach for sustained release of ciprofloxacin and its hemostatic effects.

Clotting time of lower gastro intestinal bleeding (LGIB) can be reduced by using simple, cost-effective, and naturally occurring halloysite nanotubes (HNTs). The present study aimed to decrease the clotting time by the application of chitosan (CHT) and its microcomposites (MCs) prepared by suspension emulsification technique with HNTs (CHT/HNTs MC). Physicochemical properties, X-Ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and percentage release of ciprofloxacin from CHT/HNTs MCs was evaluated. In-vitro procoagulant activity of CHT, HNTs and their complexes CHT/HNTs MCs was performed on rabbit blood which was confirmed by a rat tail amputation. Direct relation of HNTs was observed for the whole-blood clotting kinetics i.e., 2% HNTs showed a maximum 66.0% increase in the clotting ability as compared with pure CHT. Interestingly, rat-tail amputation studies showed comparative results of CHT, HNTs, and CHT/HNTs MCs. A total of 75% permeation of ciprofloxacin of CHT/HNTs MCs on rat intestinal membrane was observed within 3 h, confirming their SR behavior. Furthermore, improved hemostatic and clotting properties were CHT/HNTs MC1 > CHT/HNTs MC2 > CHT/HNTs MC3 > CHT > HNTs, respectively. Thus, it provided the control of bleeding disorders in LGIB with any antibacterial agents, particularly ciprofloxacin.

Comparison of Ultrasonic Dissection and Suture Ligation for Mesoappendix in Laparoscopic Appendectomy.

Objective To compare the use of ultrasonic dissector and suture ligation for mesoappendix in laparoscopic appendectomy in terms of mean operative time and per-operative bleed. Methodology This was a randomized controlled trial conducted at Surgical Unit II, Holy Family Hospital over a period of six months. All patients with the diagnosis of acute appendicitis who presented in the emergency department of Holy Family Hospital on the call days of Surgical Unit II undergoing laparoscopic appendectomy were included in the study. After taking informed consent about the respective procedure, patients were allocated to two groups using computer-generated random numbers. Group A was operated using harmonic scalpel and in Group B suture ligation was done. Total time required to ligate the mesoappendix or to cauterize it using the harmonic scalpel was measured in minutes. Data was entered and analyzed in SPSS version 21.0 (IBM Corp., Armonk, NY). Results A total of 110 patients were enrolled in the study according to the inclusion criteria of the study. Patients were randomly divided into two equal groups. Patients in Group A were operated using harmonic scalpel whereas patients in Group B were operated by suture ligation for dealing the mesoappendix in laparoscopic appendectomy. Mean operative time to ligate the mesoappendix for Group A patients was 1.56 (SD = 0.68) minutes while that of Group B was 21.07 (SD = 2.84) minutes. There was no per-operative bleeding in case of Group A while its incidence was 24% of patients in Group B. Results were statistically significant. Conclusion The conclusion of the study is that the use of harmonic scalpel was better than suture ligation for ligating the mesoappendix in laparoscopic appendectomy in terms of mean operative time and per operative bleed, hence it's preferable over the later in laparoscopic appendectomy.

Challenges of continuation of live liver donor programme during COVID-19 pandemic in Pakistan: outcomes and lessons learned.

BACKGROUND: COVID-19 pandemic has globally affected healthcare including the transplantation programmes. MATERIALS AND METHODS: We retrospectively studied the impact of COVID-19 on live liver donor (LLD) programme at liver transplant centre in Gambat, Pakistan. Standard operative procedures (SOPs) including COVID-19 nasopharyngeal swab PCR, CT scans, personal protective equipment use, 6-feet distancing were developed for LLD and transplant team to mitigate COVID-19 exposure. We compared the complications, healthcare utilisation (hospital stay, readmission) and mortality between two LLD cohorts-before and during COVID-19 pandemic from March 2019 to December 2020. RESULTS: During study period 300 LLD surgeries were performed. There was an increase in rate of LLDs from 132 (44%) in pre-COVID to 168 (56%) during COVID-19 era. Average numbers of transplants per month performed during pre-COVID and during COVID-19 era were 10.1 and 14, respectively. No donor has developed COVID-19 infection during hospitalisation. Rate of all LLD complications (32 (21.47%) and 49 (29.16%), p=0.43), uneventful discharges (120/168 (71.4%) and 88/132 (66.6%), p<0.05), mean hospital stay (6±2 days and 5±2 days, p=0.17) and readmission (5 (4%) and 3 (1.8%), p=0.43) were similar during the pre-COVID and COVID-19 era. No donor mortality was observed during study period. CONCLUSION: With the implementation of mindful SOPs, rate of LLD increased without any case of COVID-19 infection. Our SOPs were helpful in continuation of LLD programme in a developing country during COVID-19 pandemic.

Integration of entomopathogenic fungi and eco-friendly insecticides for management of red palm weevil, Rhynchophorus ferrugineus (Olivier).

Red palm weevil (Rhynchophorus ferrugineus) is a voracious pest of date palm worldwide. Pakistan ranks sixth in date palm production globally. Losses to date palm plantations in Pakistan sometimes surpass 10%-20%. Most of the traditional management strategies used by farmers have been found insignificant to combat this voracious pest. The entomopathogenic fungi, Beauveria bassiana [QA-3(L) and QA-3(H)] and insecticides, Nitenpyram (Active 10% SL) [NIT (L) and NIT (H)] were applied to larval (2nd, 4th, and 6th), pupal and adult stages of R. ferrugienus. Integration or alone application of fungi with insecticides at different concentration under laboratory conditions. Combined application was depicted additive and synergistic interactions. Contrarily, highest cumulative mortality (100%) was recorded in 2nd instar larvae as compared to later instar larvae at combined application. The maximum pupal and adult mortality remained 89% and 66% respectively after treatment with [QA-3 (H) + NIT (L)]. The combination of B. bassiana at higher concentration whereas Nitenpyram at lower dose was found more lethal to larvae, pupae and adults of R. ferrugineus. This signifies the need of combining B. bassiana and bio-rational insecticides that can reduce the cost of management with least harm to environment and natural enemies.

Two new antioxidant bergenin derivatives from the stem of Rivea hypocrateriformis.

Two new bergenin derivatives, named rivebergenin A and B (1, and 2), together with two known compounds, bergenin (3) and norbergenin (4) were isolated from the stem of Rivea hypocrateriformis (Desr.) Choisy. The structures of the new compound have been assigned from (1)H and (13)C NMR spectra, DEPT, and by 2D COSY, HMQC, and HMBC experiments. Compounds 1-4 showed the strong antioxidant activity.