Fully-automated deep learning-based flow quantification of 2D CINE phase contrast MRI.

OBJECTIVES: Time-resolved, 2D-phase-contrast MRI (2D-CINE-PC-MRI) enables in vivo blood flow analysis. However, accurate vessel contour delineation (VCD) is required to achieve reliable results. We sought to evaluate manual analysis (MA) compared to the performance of a deep learning (DL) application for fully-automated VCD and flow quantification and corrected semi-automated analysis (corSAA). METHODS: We included 97 consecutive patients (age = 52.9 ± 16 years, 41 female) with 2D-CINE-PC-MRI imaging on 1.5T MRI systems at sinotubular junction (STJ), and 28/97 also received 2D-CINE-PC at main pulmonary artery (PA). A cardiovascular radiologist performed MA (reference) and corSAA (built-in tool) in commercial software for all cardiac time frames (median: 20, total contours per analysis: 2358 STJ, 680 PA). DL-analysis automatically performed VCD, followed by net flow (NF) and peak velocity (PV) quantification. Contours were compared using Dice similarity coefficients (DSC). Discrepant cases (> ± 10 mL or > ± 10 cm/s) were reviewed in detail. RESULTS: DL was successfully applied to 97% (121/125) of the 2D-CINE-PC-MRI series (STJ: 95/97, 98%, PA: 26/28, 93%). Compared to MA, mean DSC were 0.91 ± 0.02 (DL), 0.94 ± 0.02 (corSAA) at STJ, and 0.85 ± 0.08 (DL), 0.93 ± 0.02 (corSAA) at PA; this indicated good to excellent DL-performance. Flow quantification revealed similar NF at STJ (p = 0.48) and PA (p > 0.05) between methods while PV assessment was significantly different (STJ: p < 0.001, PA: p = 0.04). A detailed review showed noisy voxels in MA and corSAA impacted PV results. Overall, DL analysis compared to human assessments was accurate in 113/121 (93.4%) cases. CONCLUSIONS: Fully-automated DL-analysis of 2D-CINE-PC-MRI provided flow quantification at STJ and PA at expert level in > 93% of cases with results being available instantaneously. KEY POINTS: • Deep learning performed flow quantification on clinical 2D-CINE-PC series at the sinotubular junction and pulmonary artery at the expert level in > 93% of cases. • Location detection and contouring of the vessel boundaries were performed fully-automatic with results being available instantaneously compared to human assessments which approximately takes three minutes per location. • The evaluated tool indicates usability in daily practice.

Distribution and antibiotic sensitivity pattern of Mycobacterium tuberculosis isolates from children, enrolled in a tertiary care hospital.

The present study was planned to assess the distribution of tuberculosis in children and evaluate the antimycobacterial sensitivity pattern of Mycobacterium tuberculosis (MTB) isolates from pediatric patients. A total number of 1718 pediatric patients suspected of Mycobacterium tuberculosis were enrolled in the Institute of Child Health and Children's Hospital, Lahore during 2016-17. Out of 1718, only 710 different types of samples were tested for MTB. The samples were processed using bacteriology and GeneXpert along with the chest X-ray and clinical picture of the patients. The sensitivity pattern of Streptomycin, Isoniazid, Rifampicin and Ethambutol (SIRE) was determined using BACTEC MGIT 960. Total patients were divided into four groups including group A (birth to 12 months), B (1 to 5 years), C (6 to 10 years), and D (11 to 15 years). Out of 710, 106 (55 females and 51 males) were declared positive and 604 negative for tuberculosis. Out of 106 positive cases, 89 (83.96%) were sensitive to Rifampicin and 17 (16.04%) were resistant. Only, 04 (3.77%) were resistant to both Rifampicin and Isoniazid and declared as multidrug-resistant (MDR). It was concluded that children of age 11 to 15 years were more prone to MTB and a minimum percentage of MDR isolates was recorded in age group A (birth to 12 months).

Appraisal of anti-mycobacterial potential against MDR-MTB in pediatric patients, cytotoxicity and mutagenicity of Aloe vera and Allium sativum.

The purpose of the studies was to evaluate an in-vitro anti-mycobacterial activity of Aloe vera and Allium sativum against MDR-MTB, their cytotoxicity and mutagenicity. Four extracts of Aloe vera and Allium sativum were prepared by Soxhlet apparatus and their minimum inhibitory concentrations (MIC's) were determined by BACTEC MGIT960 system against multi drug resistant Mycobacterium tuberculosis (MDR-MTB) isolates, collected from pediatric patients. Fractions of Aloe vera and Allium sativum extracts were separated using glass column chromatography, followed by evaluation of cytotoxicity and mutagenicity by tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Ames test, respectively. Out of four extracts, ethanol extracts of Aloe vera and Allium sativum exhibited activity at MIC 5mg/mL to 7mg/mL and 3mg/mL to 5mg/mL, respectively and IC50 by MTT assay for combination of all fractions were 278.3mcg/100µL and 270.8mcg/100µL and in Ames assay M.I of TA98 were 0.14 and 0.07 and M.I of TA100 were 1.14 and 0.44, respectively. Aloe vera and Allium sativum extracts showed anti-mycobacterial activity against MDR-MTB isolates so, MIC of ethanol extracts of each plant and fractions of column chromatography had been checked. The MTT and Ames tests depicted that ethanol extracts of Aloe vera and Allium sativum were non-cytotoxic and non-mutagenic, and can be used in treatment of patients suffering from MDR-MTB.

Hematologic adverse effects and efficacy monitoring in chronic Hepatitis C patients treated with interferon and ribavirin combination therapy.

180 million people are affected by chronic Hepatitis C Virus infection globally and more than 50 million in South East Asia. Combination of Interferon and Ribavirin is the current anti-HCV therapy in practice and is associated with certain hematologic adverse effects. In this concurrent observational study the incidence rate of major hematologic adverse effects and efficacy outcomes of Interferon and Ribavirin combination therapy was evaluated in 288 chronic hepatitis C patients at Lahore General Hospital. Levels of Hb, TLC, and Platelets counts were monitored for hematologic adverse effects monitoring, whereas, ALT, AST and bilirubin levels were monitored for efficacy. PCR was done at week 4, 12 &36 for therapeutic success evaluation. A significant reduction in Hb levels (p<0.05) was observed after week 4, 8 and 12 of therapy. Frequency of anemia increased in both genders with body weight <65kg and platelet count <150,000/mm3. End Treatment Response (ETR) was achieved in 64.5%. Anemia was the major side effect of the combination therapy particularly in the males. Higher ETR was observed in patients who achieved RVR and were <50 years of age.

Preparation of QP4VP-b-LCP liquid crystal block copolymer and its application as a biosensor.

The interface between nematic liquid crystal, 4-cyano-4'-pentylbiphenyl (5CB), and water in a transmission electron microscopy (TEM) grid cell coated with QP4VP-b-LCP (quaternized poly(4-vinylpyridine) (QP4VP) and poly(4-cyanobiphenyl-4'-oxyundecylacrylate) (LCP)) was examined for protein and DNA detection. QP4VP-b-LCP was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Quaternization of P4VP with iodomethane (CH3I) made it a strong cationic polyelectrolyte and allowed QP4VP-b-LCP to form complexes with oppositely charged biological species. Several proteins, such as bovine serum albumin (BSA), hemoglobin (Hb), α chymotrypsinogen-A (ChTg), and lysozyme (LYZ), were tested for nonspecific protein detection. By injecting the protein solutions into the TEM grid cell, the initial homeotropic orientation of the TEM grid cell changed to a planar orientation above their isoelectric points (PIs) due to electrostatic interactions between QP4VP (+charge) and proteins (-charge), which did not occur below the PIs of the tested proteins. Their minimum concentrations at which the homeotropic to planar configurational change (H-P change) occurred were 0.01, 0.02, 0.03, and 0.04 wt.% for BSA, ChTg, Hb, and LYZ, respectively. One of the strong anionic polyelectrolytes, deoxyribonucleic acid (DNA) (due to the phosphate deoxyribose backbone) was also tested. A H-P change was observed with as little as 0.0013 wt.% salmon sperm DNA regardless of the pH of the cell. A H-P change occurred in 5CB and was observed by polarized optical microscopy. This simple and inexpensive setup for nonspecific biomaterial detection provides the basic idea for developing effective selective biosensors by introducing specific binding groups, such as the aptamer and antibody.

Mutagenic and cytotoxic potential of Endosulfan and Lambda-cyhalothrin - in vitro study describing individual and combined effects of pesticides.

Excessive use of pesticides poses increased risks to non target species including humans. In the developing countries, lack of proper awareness about the toxic potential of pesticides makes the farmer more vulnerable to pesticide linked toxicities, which could lead to diverse pathological conditions. The toxic potential of a pesticide could be determined by their ability to induce genetic mutations and cytotoxicity. Hence, determination of genetic mutation and cytotoxicity of each pesticide is unavoidable to legislate health and safety appraisal about pesticides. The objective of current investigation was to determine the genotoxic and cytotoxic potential of Endosulfan (EN) and Lambda-cyhalothrin (LC); individually and in combination. 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay was utilized to determine cytotoxicity, while two mutant histidine dependent Salmonella strains (TA98, TA100) were used to determine the mutagenicity of EN and LC. Moreover, mutagenicity assay was conducted with and without S9 to evaluate the effects of metabolic activation on mutagenicity. Even though a dose dependent increase in the number of revertant colonies was detected with EN against both bacterial strains, a highly significant (p<0.05) increase in the mutagenicity was detected in TA98 with S9. In comparison, data obtained from LC revealed less mutagenic potential than EN. Surprisingly, the non-mutagenic individual-concentrations of EN and LC showed dose dependent mutagenicity when combined. Combination of EN and LC synergistically induced mutagenicity both in TA98 and TA100. MTT assay spotlighted comparable dose dependent cytotoxicity effects of both pesticides. Interestingly, the combination of EN and LC produced increased reversion and cytotoxicity at lower doses as compared to each pesticide, concluding that pesticide exposure even at sub-lethal doses can produce cytotoxicity and genetic mutations, which could lead to carcinogenicity.

Comprehensive Analysis of Curcumin Zinc Oxide Nanoparticles, Synthesis, Characterization, and Cytogenotoxic Profiling.

Curcumin from turmeric (Curcuma longa) has traditionally been used due to its pharmacological properties, such as anticancer, anti-inflammatory, cholesterol-lowering, and antioxidant activities, but has had limitations in use due to low bioavailability. Nanoparticles have protuberant efficacies to diagnose or cure a variety of diseases, including tumors, by fine-tuning their size, structure, and physicochemical characteristics. This study aims to develop a new dosage form of curcumin nanoparticles with zinc oxide to enhance its therapeutic efficacy against cancer and cause no damage to genetics. Curcumin zinc oxide nanoparticles were prepared and characterized by using a Zeta sizer, ultraviolet (UV)-spectrophotometer, scanning electron microscope (SEM), and Fourier transform infrared (FTIR) spectroscopy. Different concentrations range from 40 to 0.078 µg/mL, and these nanoparticles were evaluated for their anticancer activity by colorimetric analysis (MTT assay) on normal (Vero) and cancerous cell lines (MCF-7) and genotoxicity by the comet assay. The spherical-shaped curcumin zinc oxide nanoparticles of 189 nm size were prepared with characteristic functional groups. The selectivity index of curcumin zinc oxide nanoparticles, calculated from IC50 values, is 4.60 > 2.0, showing anticancer potential comparable to tamoxifen. The genetic damage index of the highest concentration (40 µg/mL) of curcumin zinc oxide nanoparticles was 0.08, with a percent fragmentation of 8%. The results suggest that nanoparticles of curcumin zinc oxide produced better anticancer effects and did not cause any significant damage to the DNA. Consequently, further research is required to ensure the development of a safe and quality dosage form of nanoparticles for proper utilization.

Carvacrol-Fabricated Chitosan Nanoparticle Synergistic Potential with Topoisomerase Inhibitors on Breast and Cervical Cancer Cells.

Breast and cervical cancers are the most common heterogeneous malignancies in women. Chemotherapy with conventional drug delivery systems having several limitations along with development of multidrug resistance compelled us to seek out targeted therapeutics. Nanoparticles are suitable substitutes to circumvent multidrug resistance for the targeted treatment of cancer. The current study was aimed to investigate the anticancer effect of carvacrol-loaded chitosan nanoparticles with topoisomerase inhibitors. The average size of carvacrol-loaded chitosan nanoparticles was found to be 80 nm with 24.7 mV ζ-potential, and maximum absorbance was observed at 275 nm. Among all drug combinations, the carvacrol nanoparticles with the doxorubicin combination group exerted greater dose-dependent growth inhibition of both MCF-7 and HeLa cells as compared to single carvacrol nanoparticles and doxorubicin. Combination index values of carvacrol nanoparticles and the doxorubicin combination group showed a strong synergistic effect as they were found to be between 0.2 and 0.4, 0.31 for MCF-7 and 0.34 for HeLa cells. The carvacrol nanoparticles in combination with doxorubicin on MCF-7 cells reduced the dose 16.32-fold for carvacrol nanoparticles and 4.09-fold for doxorubicin at 6.23 µg/mL IC50, while on HeLa cells, this combination reduced the dose 13.18-fold for carvacrol nanoparticles and 3.83-fold for doxorubicin at 9.33 µg/mL IC50. As the dose reduction values were greater than 1, they indicated favorable dose reduction. It was concluded that the combination of carvacrol-loaded chitosan nanoparticles with topoisomerase inhibitors may represent an innovative and promising strategy to improve the efficacy, resistance, and targeted delivery of chemotherapeutics in cancer.

Synergistic antibacterial activity of carvacrol loaded chitosan nanoparticles with Topoisomerase inhibitors and genotoxicity evaluation.

The increasing prevalence of antibiotic resistant bacteria is a significant healthcare crisis with substantial socioeconomic impact on global community. The development of new antibiotics is both costly and time-consuming prompting the exploration of alternative solutions such as nanotechnology which represents opportunities for targeted drug delivery and reduced MIC. However, concerns have arisen regarding genotoxic effects of nanoparticles on human health necessitating an evaluation of nanoparticle induced DNA damage. This study aimed to investigate the antibacterial potential of already prepared, characterized chitosan nanoparticles loaded with carvacrol and their potential synergism with Topoisomerase II inhibitors against S. aureus, E. coli and S. typhi using agar well diffusion, microdilution and checkerboard method. Genotoxicity was assessed through comet assay. Results showed that both alone and drug combinations of varying concentrations exhibited greater zones of inhibition at higher concentrations. Carvacrol nanoparticles combined with ciprofloxacin and doxorubicin significantly reduced MIC compared to the drugs used alone. The MIC50 values for ciprofloxacin were 35.8 µg/ml, 48.74 µg/ml, 35.57 µg/ml while doxorubicin showed MIC50 values of 20.79 µg/ml, 34.35 µg/ml, 25.32 µg/ml against S. aureus, E. coli and S. typhi respectively. The FICI of ciprofloxacin and doxorubicin with carvacrol nanoparticles found ≤ 0.5 Such as 0.44, 0.44,0.48 for ciprofloxacin and 0.45, 0.45, 0.46 for doxorubicin against S. aureus, E. coli and S. typhi respectively revealed the synergistic effect. The analysis of comet assay output images showed alteration of DNA at high concentrations. Our results suggested that carvacrol nanoparticles in combination with Topoisomerase inhibitors may prevent and control the emergence of resistant bacteria with reduced dose.

Chemical insights into the synthetic chemistry of five-membered saturated heterocycles-a transition metal-catalyzed approach.

Drug design and delivery is primarily based on the hunt for new potent drug candidates and novel synthetic techniques. Recently, saturated heterocycles have gained enormous attention in medicinal chemistry as evidenced by the medicinal drugs listed in the FDA Orange Book. Therefore, the demand for novel saturated heterocyclic syntheses has increased tremendously. Transition metal (TM)-catalyzed reactions have remained the prime priority in heterocyclic syntheses for the last three decades. Nowadays, TM catalysis is well adorned by combining it with other techniques such as bio- and/or enzyme-catalyzed reactions, organocatalysis, or using two different metals in a single catalysis. This review highlights the recent developments of the transition metal-catalyzed synthesis of five-membered saturated heterocycles.

Isolation of alkaloidal and glycosidal fractions from leaves of Trigonella foenum-graecum L. cv. Desi indigenous to Pakistan for antiprostaglandin evaluation as substitute of nonsteroidal anti-inflammatory drugs.

ETHNOPHARMACOLOGICAL RELEVANCE: Trigonella foenum graecum (fenugreek) has been in use for a long time as a traditional medicine and natural food additive. The reported gastro-protective property makes it unique among other herbs. Seeds and leaves have been shown to exert significant antiatherogenic, antidiabetic, antianorexic, antioxidant, anticarcinogenic, antihyperlipidemic, galactogogue and anti-inflammatory effects in several animal and human models. But its use as a substitute for ulcerative nonsteroidal anti-inflammatory drugs needs to be confirmed. AIM OF THE STUDY: Nonsteroidal anti-inflammatory drugs (NSAIDs) are in common use in treating inflammation associated with a variety of ailments, fever and pain such as menstrual cramps, back pain, arthritic pain and headaches. Their toxicity profile includes the risk of severe gastro-intestinal adverse events like increased bleeding tendency, ulceration, perforation, etc. Conventional NSAIDs have also been reported to reduce the glomerular filtration rate (GFR) by affecting afferent arterioles in nephrons. Exacerbated potassium levels were noted in patients using NSAIDs concomitantly with antihypertensive drugs belonging to the angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) classes. In this context, the need of the hour is to discover and isolate new compounds from the reported medicinal plants for evaluation of antiprostaglandin potential and safety profile in terms of the hepato-renal system. These compounds may be used as substitutes for NSAIDs in the future management of inflammation and pain with therapeutic equivalency and organ safety. In this scenario, the present study aimed to assess the antiprostaglandin potential of alkaloidal and glycosidal fractions from the leaves of Trigonella foenum-graecum L. cv. Desi variety, indigenous to Pakistan, in albino mice along with safety profile. The herb has been used as folk medicine since ancient times for treating inflammation and pain. MATERIAL AND METHODS: Alkaloidal and glycosidal fractions were separated from a methanol extract of leaves of the fenugreek Desi variety. After separation of fractions, their subsiding effects on carrageenan-induced inflammation, air pouch exudate prostaglandin-E2 levels, Brewer's yeast induced pyrexia and acetic acid induced abdominal constrictions were assessed in adult male albino mice. The safety profile of fractions was assessed by measuring their effects on mice sera hepato-renal biomarkers. RESULT: Alkaloidal fraction of T. foenum Desi variety was found to be significantly effective in reducing inflammation, air pouch exudate PGE2 levels, fever (≤37 °C) and pain by inhibiting writhes (up to 96.58%) Gradual inhibition of paw edema was observed 1-6 h post-dose, with maximum reduction percentages of 62.82% and 62.57% for 100 mg and 200 mg, respectively. Both fractions did not disturb the normal physiology of the hepato-renal system by showing normal biomarker values. CONCLUSION: In summary, the results demonstrate the potent antiprostaglandin potential of the alkaloidal fraction of gastroprotective fenugreek "Desi" leaves with hepato-renal system safety and hence justify its use as a substitute for ulcerative nonsteroidal anti-inflammatory drugs.

Soluble laticifer proteins from Calotropis procera as an effective candidates for antimicrobial therapeutics.

Calotropis procera is a latex-producing plant with plenty of pharmacologically active compounds. The principal motivation behind this study was to separate and characterize laticifer proteins to check their antimicrobial potential. Laticifer proteins were separated by gel filtration chromatography (GFC) and investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The SDS-PAGE assay detected proteins of molecular weights of 10 to 30 kDa but most of them were in the range of 25 to 30 kDa. The soluble laticifer proteins (SLPs) were tested against Gram-positive bacteria i.e., Streptococcus pyogenes and Staphylococcus aureus whereas Escherichia coli and Pseudomonas aeruginosa were tested as Gram-negative bacteria, we determined a profound anti-bacterial activity of these proteins. In addition, SLPs were also investigated against Candida albicans via the agar disc diffusion method which also showed significant anti-fungal activity. SLP exhibited antibacterial activity against P. aeruginosa, E. coli, and S. aureus with a minimum inhibitory concentration (MIC) of 2.5 mg/mL for each, while MIC was found at 0.625 mg/mL for S. pyogenes and 1.25 mg/mL for C. albicans. Moreover, enzymatic activity evaluation of SLP showed the proteolytic nature of these proteins, and this proteolytic activity was greatly enhanced after reduction which might be due to the presence of cysteine residues in the protein structure. The activity of the SLPs obtained from the latex of C. procera can be associated with the involvement of enzymes either proteases or, protease inhibitors and/or peptides.

Functional Studies of Cytogenotoxic Potential of Laticifer Proteins of Calotropis procera against Viral Disease.

Plant products are widely used for health and disease management. However, besides their therapeutic effects, some plants also have potential toxic activity. Calotropis procera is a well-known laticifer plant having pharmacologically active proteins playing a therapeutically significant role in curing diseases like inflammatory disorders, respiratory diseases, infectious diseases, and cancers. The present study was aimed to investigate the antiviral activity and toxicity profile of the soluble laticifer proteins (SLPs) obtained from C. procera. Different doses of rubber free latex (RFL) and soluble laticifer protein (ranging from 0.019 to 10 mg/mL) were tested. RFL and SLPs were found to be active in a dose-dependent manner against NDV (Newcastle disease virus) in chicken embryos. Embryotoxicity, cytotoxicity, genotoxicity, and mutagenicity of RFL and SLP were examined on chicken embryos, BHK-21 cell lines, human lymphocytes, and Salmonella typhimurium, respectively. It was revealed that RFL and SLP possess embryotoxic, cytotoxic, genotoxic, and mutagenic activity at higher doses (i.e., 1.25-10 mg/mL), while low doses were found to be safe. It was also observed that SLP showed a rather safer profile as compared to RFL. This might be due to the filtration of some small molecular weight compounds at the time of purification of SLPs through a dialyzing membrane. We suggest that SLPs could be used therapeutically against viral disorders but the dose should be critically monitored.

Insights into the Prognostic Role of Serum Interleukin-6 and Hematobiochemical Alterations in Cattle during Recent Outbreaks of Lumpy Skin Disease in Lodhran District, Pakistan.

Lumpy skin disease (LSD) is a highly infectious disease of cattle caused by a virus of the Poxviridae family, genus Capripoxvirus. The present study was designed to determine the prognostic ability of serum IL-6 in LSD using a binary logistic regression model at baseline sampling. A 17-day cohort study was conducted on a recent outbreak of LSD among cattle in the Lodhran District of Punjab, Pakistan. Infected cattle were divided into two categories based on their clinical status on day 17 as recovered (n = 33) or unrecovered (n = 17). Nodular lesions and scab specimens (n = 50) were used for the isolation of the lumpy skin disease virus and were confirmed by PCR. In recovered animals, hematological results showed marked leukocytosis, eosinophilia, lymphocytosis, neutrophilia, and monocytopenia. However, marked erythrocytosis, leukopenia, and thrombocytopenia were observed in the unrecovered animals at the final sampling point of the study. Serum levels of total protein, albumin, and glucose were significantly higher in the recovered animals. Meanwhile, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatinine phosphokinase, total bilirubin, and direct bilirubin were found considerably higher in the unrecovered group. Receiver-operating characteristic curve analysis for serum IL-6 at baseline predicts the extended clinical conditions at the cut-off value of 85.16 pg/mL (55% specificity, 94% sensitivity, area under the curve 0.8039, respectively). In conclusion, the disease-induced hematological and biochemical alterations were significantly ameliorated in the recovered animals. In addition, the study revealed that serum IL-6 can be used as a valid marker for predicting the clinical worsening of LSD in cattle.

Pharmacological effect of Argyrolobium roseum (Camb.) Jaub & Spach extracts against lead-induced toxicity in rats.

Argyrolobium roseum (Camb.) Jaub & Spach (Papilionaceae) is a medicinal plant, cultivated in northern areas of Pakistan. The consumption of trace minerals (lead) is very toxic to the vital organs of the body, therefore the overcome of these minerals is very necessary. In this regard, this study aimed to assess the potential pharmacological effect of aqueous and ethanolic extract of Argyrolobium roseum (Camb.) Jaub & Spach against pb-induced oxidative stress, histological changes in Pb-induced rats' liver and kidney, and anti-inflammatory effect. The metal concentrations in liver and kidney homogenates were measured through atomic absorption spectrophotometer. The antioxidant activity was measured through DPPH and FRAP assay. Pb concentrations were significantly higher in liver and kidney homogenates after injection of Pb acetate was given intraperitoneally (45.2 ± 6.8 and 58.8 ± 7.9, respectively; p < .0001). The level of Pb in liver and kidney homogenates was significantly reduced by aqueous and ethanolic extracts of Argyrolobium roseum (Camb.) Jaub & Spach. The Pb + Aq-600 mg/kg-treated rats exhibited a protective effect on hepatocytes cells against Pb-induced liver injury and restored the cells of the kidney. Pb + Aq-600 mg/kg showed higher antioxidant activity as compared to other treated groups. The highest decreased MDA level was found in liver and kidney homogenate of Pb + Aq-600 mg/kg rats (11.2 ± 1.51 nmol/mg; p < .001) and GSH and CAT levels tended to normal after treatment of Pb + Aq-600 mg/kg in rats. The ALAD, ALT, AST, and ALP level were enhanced and tended to be normal after the Aq-400 and Aq-600 mg/kg treatment in Pb-exposed rats. The result showed that 600 mg/kg Aq + Pb exhibited significant (p < .001) anti-inflammatory activity. The findings of this study concluded that treatment of the aqueous extract of Argyrolobium roseum (Camb.) Jaub & Spach reduces the renal and hepatic damage in Pb-induced rats and it also decreases oxidative stress via improving antioxidant components.

An insight into recent developments of copper, silver and gold carbon dots: cancer diagnostics and treatment.

Cancer is one of the most fatal diseases globally, however, advancement in the field of nanoscience specifically novel nanomaterials with nano-targeting of cancer cell lines has revolutionized cancer diagnosis and therapy and has thus attracted the attention of researchers of related fields. Carbon Dots (CDs)-C-based nanomaterials-have emerged as highly favorable candidates for simultaneous bioimaging and therapy during cancer nano-theranostics due to their exclusive innate FL and theranostic characteristics exhibited in different preclinical results. Recently, different transition metal-doped CDs have enhanced the effectiveness of CDs manifold in biomedical applications with minimum toxicity. The use of group-11 (Cu, Ag and Au) with CDs in this direction have recently gained the attention of researchers because of their encouraging results. This review summarizes the current developments of group-11 (Cu, Ag and Au) CDs for early diagnosis and therapy of cancer including their nanocomposites, nanohybrids and heterostructures etc. All The manuscript highlights imaging applications (FL, photoacoustic, MRI etc.) and therapeutic applications (phototherapy, photodynamic, multimodal etc.) of Cu-, Ag- and Au-doped CDs reported as nanotheranostic agents for cancer treatment. Sources of CDs and metals alogwith applications to give a comparative analysis have been given in the tabulated form at the end of manuscript. Further, future prospects and challenges have also been discussed.

Attitude and Acceptance towards COVID-19 Booster Doses among Literacy Advantaged Population in Pakistan: A Cross-Sectional Study.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has affected billions of lives and is expected to impose a significant burden on the economy worldwide. Vaccination is the only way to prevent the infection. However, convincing people to get themselves vaccinated is challenging in developing countries such as Pakistan. Therefore, a cross-sectional questionnaire-based study was conducted (n = 982 participants) all over Pakistan to evaluate the perception, knowledge, attitude, and acceptance of the general public towards the SARS-CoV-2 vaccine, in general, and a booster dose of SARS-CoV-2, in particular. The highest number of participants were from the province of Punjab (84.5%), followed by Islamabad (3.8%), Sindh (3.7%), Khyber Pakhtunkhwa (2.7%), Baluchistan (2.6%), Gilgit Baltistan (1.4%), and Azad Jammu and Kashmir (1.4%). A total of 915 participants were vaccinated against COVID-19, out of which 62.2% received one booster dose, followed by double booster doses (25.5%) and single vaccine shots (12.3%). The highest number of vaccinated participants were from Punjab (85.8%), followed by Islamabad (3.9%), Sindh (2.8%); Khyber Pakhtunkhwa (2.6%); Baluchistan (2.3%); Gilgit-Baltistan (1.3%); and Azad, Jammu, and Kashmir (1.2%). Among the vaccinated individuals, 71.4% were unemployed, 27.4% were employed (653), and 1.2% were retired from service. However, no significant association was observed among genders and educational levels in regard to acceptance of the booster vaccine. The outcomes of the study revealed that the increased acceptance of booster doses of the SARS-CoV-2 vaccines among the public was associated with the intent of personal and family protection. Moreover, individuals with low socioeconomic status and pregnant females showed the least acceptance towards the vaccine inoculation. The study also revealed a decline trend of accepting SARS-CoV-2 vaccine among children.

Biosynthesis and characterization of zinc oxide nanoparticles using Nigella sativa against coccidiosis in commercial poultry.

Coccidiosis causes huge economic losses worldwide. Current study evaluated the effect of biosynthesized Zinc oxide nanoparticles (ZnONPs) using Nigella sativa, on Eimeria tenella infected broilers. Scanning electron microscopy showed spherical ZnONPs with 50-100 nm diameter, Fourier transforms infrared spectroscopy revealed the functional groups involved in the reduction of zinc acetate dihydrate to ZnONPs, UV-vis spectroscopy showed a peak at 354 nm, and Zeta potential exhibited stability at - 30 mV. A total of 150, a day-old broiler chicks were divided into 5 equal groups. Control negative: uninfected and untreated; Control positive: Infected and untreated; 3rd, 4th and 5th group were infected orally with 5 × 104 sporulated oocysts of Eimeria tenella and treated with 60 mg/kg ZnONPs, 1% Nigella sativa seeds and amprolium 125 ppm, respectively. ZnONPs significantly (p < 0.05) improved the growth performance in the infected birds and decreased the oocyst shedding and anti-coccidial index. A significant (p < 0.05) decrease in the level of aspartate transferase and alanine transferase, whereas, a significantly higher amount of antioxidants like catalase and superoxide dismutase in ZnONPs treated group was observed. Pro-inflammatory cytokines like IL-2 and TNF-α were significantly decreased by ZnONPs (p < 0.05). In conclusion, biogenic ZnONPs with Nigella sativa might have enhanced anticoccidial, antioxidant, and anti-inflammatory effects with improved growth performance.

Fluorinated triazoles as privileged potential candidates in drug development-focusing on their biological and pharmaceutical properties.

Fluorinated heterocycles have attracted extensive attention not only in organic synthesis but also in pharmaceutical and medicinal sciences due to their enhanced biological activities than their non-fluorinated counterparts. Triazole is a simple five-membered heterocycle with three nitrogen atoms found in both natural and synthetic molecules that impart a broad spectrum of biological properties including but not limited to anticancer, antiproliferative, inhibitory, antiviral, antibacterial, antifungal, antiallergic, and antioxidant properties. In addition, incorporation of fluorine into triazole and its derivatives has been reported to enhance their pharmacological activity, making them promising drug candidates. This mini-review explores the current developments of backbone-fluorinated triazoles and functionalized fluorinated triazoles with established biological activities and pharmacological properties.

Simvastatin Nanoparticles Loaded Polymeric Film as a Potential Strategy for Diabetic Wound Healing: In Vitro and In Vivo Evaluation.

INTRODUCTION: The pleiotropic effects of statins are recently explored for wound healing through angiogenesis and lymph-angiogenesis that could be of great importance in diabetic wounds. AIMS: The aim of the present study is to fabricate nanofilm embedded with simvastatin-loaded chitosan nanoparticles (CS-SIM-NPs) and to explore the efficacy of SIM in diabetic wound healing. METHODS: The NPs, prepared via ionic gelation, were 173 nm ± 2.645 in size with a zeta potential of -0.299 ± 0.009 and PDI 0.051 ± 0.088 with excellent encapsulation efficiency (99.97%). The optimized formulation (CS: TPP, 1:1) that exhibited the highest drug release (91.64%) was incorporated into the polymeric nanofilm (HPMC, Sodium alginate, PVA), followed by in vitro characterization. The optimized nanofilm was applied to the wound created on the back of diabetes-induced (with alloxan injection 120 mg/kg) albino rats. RESULTS: The results showed a significant (p < 0.05) improvement in the wound healing process compared to the diabetes-induced non-treated group. The results highlighted the importance of nanofilms loaded with SIM-NPs in diabetic wound healing through angiogenesis promotion at the wound site. CONCLUSION: Thus, CS-SIM-NPs loaded polymeric nanofilms could be an emerging diabetic wound healing agent in the industry of nanomedicines.