Exposure to Short- and Medium-Chain Chlorinated Paraffins and the Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study in Eastern China.

Toxicological studies have indicated that exposure to chlorinated paraffins (CPs) may disrupt intracellular glucose and energy metabolism. However, limited information exists regarding the impact of human CP exposure on glucose homeostasis and its potential association with an increased risk of developing gestational diabetes mellitus (GDM). Here, we conducted a prospective study with a nested case-control design to evaluate the link between short- and medium-chain CP (SCCPs and MCCPs) exposures during pregnancy and the risk of GDM. Serum samples from 102 GDM-diagnosed pregnant women and 204 healthy controls were collected in Hangzhou, Eastern China. The median (interquartile range, IQR) concentration of SCCPs was 161 (127, 236) ng/mL in the GDM group compared to 127 (96.9, 176) ng/mL in the non-GDM group (p < 0.01). For MCCPs, the GDM group had a median concentration of 144 (117, 174) ng/mL, while the control group was 114 (78.1, 162) ng/mL (p < 0.01). Compared to the lowest quartile as the reference, the adjusted odds ratios (ORs) of GDM were 7.07 (95% CI: 2.87, 17.40) and 3.34 (95% CI: 1.48, 7.53) in the highest quartile of ∑SCCP and ∑MCCP levels, respectively, with MCCPs demonstrating an inverted U-shaped association with GDM. Weighted quantile sum regression evaluated the joint effects of all CPs on GDM and glucose homeostasis. Among all CP congeners, C13H23Cl5 and C10H16Cl6 were the crucial variables driving the positive association with the GDM risk. Our results demonstrated a significant positive association between CP concentration in maternal serum and GDM risk, and exposure to SCCPs and MCCPs may disturb maternal glucose homeostasis. These findings contribute to a better understanding of the health risks of CP exposure and the role of environmental contaminants in the pathogenesis of GDM.

Color-tunable stable quasi-2D hybrid metal halide perovskites: synthesis, characterization, and optical analysis.

Metal halide perovskites show remarkable optical properties and useful applications in optoelectronic devices. However, the instability of three-dimensional (3D) metal halide perovskites limits their applications, leading to the emergence of more stable two-dimensional (2D) metal halide perovskites. Herein, we present a facile synthesis of the 2D hybrid metal halide perovskite (EDA)(MA)n-1PbnBr3n+1 (EDA: ethylene diammonium, MA: methylammonium), where n = 1-6, and MAPbBr3 perovskite layers using an anti-solvent co-precipitation technique. The synthesized materials exhibited tunable optical properties, and the color emissions of pure EDAPbBr4 and (EDA)(MA)2Pb3Br10 perovskites were successfully tailored by altering halide anion layers. The band gap decreases as the value of n in the (EDA)(MA)n-1PbnBr3n+1 compound increases from 1 to 6. The as-prepared materials were characterized using X-ray diffraction (XRD) technique, Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-Vis), photoluminescence spectroscopy (PL), scanning electron microscopy (SEM), and energy dispersive X-ray analysis (EDX). Finally, the stability of the 2D hybrid metal halide perovskite structures was evaluated under ambient conditions over different periods. Their tunable color emission was investigated and robust fluorescence was observed after 55 days. Thus, this study provides valuable insights into the synthesis and characterization of 2D hybrid metal halide perovskites for tunable color emission, highlighting their potential for use in various optoelectronic applications.

Insight into potent TLR2 inhibitors for the treatment of disease caused by Mycoplasma pneumoniae based on machine learning approaches.

Mycoplasma pneumoniae (MP) is one of the most common pathogens that causes acute respiratory tract infections. Children experiencing MP infection often suffer severe complications, lung injury, and even death. Previous studies have demonstrated that Toll-like receptor 2 (TLR2) is a potential therapeutic target for treating the MP-induced inflammatory response. However, the screening of natural compounds has received more attention for the treatment of bacterial infections to reduce the likelihood of bacterial resistance. Herein, we screened compounds by combining molecular docking and machine learning approaches to find potential lead compounds for treating MP infection. First, all compounds were docked with the TLR2 receptor protein to screen for potential candidates. To predict drug bioactivity, a machine learning model (random forest) was trained for TLR2 inhibitors to obtain the predictive model. The model achieved significant squared correlation coefficient (R2) values for the training set (0.85) and validation set (0.84) of compounds. The developed machine learning model was then used to predict the pIC50 values of the top 50 candidates from the Traditional Chinese compounds and Discovery Diversity sets of compounds. As a result, these compounds are capable of inhibiting the inflammatory response induced by MP. However, prior to bringing these compounds to market, it is necessary to verify these results with additional biological testing, including preclinical and clinical studies. Moreover, the present study provides a theoretical basis for the use of natural compounds as potential candidates to treat pneumonia caused by MP.

Herbal Formulation Comprised of Methanol Extracts of Tribulus terristris L. and Zingiber officinale Roscoe Has Antihypertensive Effects.

People prefer to use medicinal plants rather than chemical compounds because they are low cost and have fewer adverse events. Zingiber officinale Roscoe is a natural dietary rhizome with anti-oxidative, anti-inflammatory and anti-carcinogenic properties. Tribulus terrestris L. has been used for the treatment of impotence, to enhance sexual drive and performance and for its diuretic and uricosuric effects. The aim of this study was to evaluate the combined effect of 2 extracts, Tribulus terristris and Zingiber officinale (TZ) for antioxidant, enzyme modulation, liver function, kidney function, blood profile and anti-hypertensive effects, which may pave the way for possible therapeutic applications. Antioxidant potential was measured with the 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical method antioxidant assay (DPPH) and kojic acid was used as the standard drug for tyrosine inhibition assay. The effect of TZ on biochemical parameters of the liver (alanine transferase [ALT], alkaline phosphatase [ALP], aspartate aminotransferase [AST], total serum protein, total serum albumin, serum bilirubin), kidney (blood urea and creatinine) and hematology (hemoglobin, red blood cells [RBC], platelets, thin-layer chromatography, neutrophils, eosinophils, lymphocytes, monocytes, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration) of Wister rats were studied by administering 100, 250 and 500 mg/kg-1 body weight TZ dose orally for 28 days. Antihypertensive effects were measured by the invasive method. The results showed that the scavenging percentage of TZ was 78.5 to 80.4, with an IC50 value of 1166.7 µg/ ml and tyrosinase inhibition was 72% compared with 93% for kojic acid. Different doses (100, 250 and 500 mg/kg) did not show an increase in serum biomarkers of liver and renal parameters. A significant increase in hemoglobin, erythrocytes, hematocrit, white blood cells (WBC) and lymphocytes with no significant increase/decrease in platelet count was observed but blood pressure was significantly decreased. Therefore, we concluded that TZ is safe and can be used in the treatment of hypertension.

Exploring the Therapeutic Properties of Alga-Based Silver Nanoparticles: Anticancer, Antibacterial, and Free Radical Scavenging Capabilities.

The current study was designed to evaluate the antioxidant, anticancer and antimicrobial activities of silver nanoparticles (AgNPs) biosynthesized by Spirulina platensis extract. The biosynthesized silver nanoparticles were characterized using Fourier transform infrared (FT-IR) analysis, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD) analysis. The antioxidant activity of the biosynthesized AgNPs were determined via DPPH radical scavenging assay while its anticancer activity was determined using the MTT assay. The antimicrobial activity of the biosynthesized AgNPs were analyzed by disc diffusion method. Spirulina platensis acts as a reducing and capping agent. The efficacy of silver nanoparticles (AgNPs) in inhibiting the growth of Gram-negative bacteria, specifically Acetobacter, Klebsiella, Proteus vulgaris, and Pseudomonas aeruginosa, was assessed by the utilisation of the diffusion method. The study aimed to evaluate the efficacy of biosynthesized silver nanoparticles (AgNPs) against many strains of Pseudomonas aeruginosa bacteria. The findings of the study revealed that when administered in doses of 50 µl, 75 µl, and 100 µl, the largest observed zone of inhibition corresponded to measurements of 10.5 mm, 14 mm, and 16 mm, respectively. A zone of inhibition with dimensions of 8 mm, 10.5 mm, and 12 mm was detected during testing against Acetobacter at concentrations of 50 µl, 75 µl, and 100 µl, respectively. The findings also indicate that there is a positive correlation between the concentration of AgNP and the DPPH scavenging ability of silver nanoparticles. The percentage of inhibition observed at concentrations of 500 µg/ml, 400 µg/ml, 300 µg/ml, 200 µg/ml, and 100 µg/ml were recorded as 80±1.98, 61±1.98, 52±1.5, 42±1.99, and 36±1.97, respectively. In addition, it was observed that the silver nanoparticles exhibited the greatest antioxidant activity at a concentration of 500 g/ml, with a measured value of 80.89±1.99. The IC-50 values, representing the inhibitory concentration required to achieve 50 % inhibition, were found to be 8.16, 19.15, 30.14, 41.13, and 63.11 at inhibition levels of 36±1.97, 42±1.99, 52±1.5, 61±1.98, and 80±1.98, respectively.

Advancing Brain Tumor Classification through Fine-Tuned Vision Transformers: A Comparative Study of Pre-Trained Models.

This paper presents a comprehensive study on the classification of brain tumor images using five pre-trained vision transformer (ViT) models, namely R50-ViT-l16, ViT-l16, ViT-l32, ViT-b16, and ViT-b32, employing a fine-tuning approach. The objective of this study is to advance the state-of-the-art in brain tumor classification by harnessing the power of these advanced models. The dataset utilized for experimentation consists of a total of 4855 images in the training set and 857 images in the testing set, encompassing four distinct tumor classes. The performance evaluation of each model is conducted through an extensive analysis encompassing precision, recall, F1-score, accuracy, and confusion matrix metrics. Among the models assessed, ViT-b32 demonstrates exceptional performance, achieving a high accuracy of 98.24% in accurately classifying brain tumor images. Notably, the obtained results outperform existing methodologies, showcasing the efficacy of the proposed approach. The contributions of this research extend beyond conventional methods, as it not only employs cutting-edge ViT models but also surpasses the performance of existing approaches for brain tumor image classification. This study not only demonstrates the potential of ViT models in medical image analysis but also provides a benchmark for future research in the field of brain tumor classification.

Enhanced Intestinal Permeability of Cefixime by Self-Emulsifying Drug Delivery System: In-Vitro and Ex-Vivo Characterization.

BACKGROUND: Cefixime (CFX) belongs to a group of third-generation cephalosporin antibiotics with low water solubility and low intestinal permeability, which ultimately leads to significantly low bioavailability. AIM: This study aimed to increase solubility, improve drug release, and intestinal permeability of CFX by loading into SEDDS. METHODS: Suitable excipients were selected based on drug solubility, percent transmittance, and emulsification efficiency. Pseudo-ternary phase diagram was fabricated for the identification of effective self-emulsification region. The best probably optimized formulations were further assessed for encumbered drug contents, emulsification time, cloud point measurement, robustness to dilution, mean droplet size, zeta potential, polydispersity index (PDI), and thermodynamic and chemical stability. Moreover, in vitro drug release studies and ex vivo permeation studies were carried out and apparent drug permeability Papp of different formulations was compared with the marketed brands of CFX. RESULTS: Amongst the four tested SEDDS formulations, F-2 formulation exhibited the highest drug loading of 96.32%, emulsification time of 40.37 ± 3 s, mean droplet size of 19.01 ± 1.12 nm, and demonstrated improved long-term thermodynamic and chemical stability when stored at 4 °C. Release studies revealed a drug release of 97.32 ± 4.82% within 60 min in simulated gastric fluid. Similarly, 97.12 ± 5.02% release of CFX was observed in simulated intestinal fluid within 120 min; however, 85.13 ± 3.23% release of CFX was observed from the marketed product. Ex vivo permeation studies displayed a 2.7-fold increase apparent permeability compared to the marketed product in 5 h. CONCLUSION: Owing to the significantly improved drug solubility, in vitro release and better antibacterial activity, it can be assumed that CFX-loaded SEDDS might lead to an increased bioavailability and antibacterial activity, possibly leading to improved therapeutic effectiveness.

Short- and medium-chain chlorinated paraffins in agricultural and industrial soils from Shanghai, China: surface and vertical distribution, penetration behavior, and health risk assessment.

The widespread contamination of chlorinated paraffins (CPs) of the soil environment has raised global concern due to their highly persistent and toxic properties. However, little information is available regarding these industrial toxicants' spatial-vertical distribution and penetration potentials. In this study, short- and medium-chain chlorinated paraffins (SCCPs and MCCPs, respectively) were analyzed in pooled surface and core soils (0-45 cm) samples collected from agricultural and industrial areas in Shanghai. ∑SCCP concentrations in agricultural and industrial surface soils ranged from 52.6 to 237.6 and 98.3 to 977.1 ng/g dry weight (dw), respectively. ∑MCCP levels were comparatively higher and ranged from 417.2 to 1690.8 and 370.9 to 10,712.7 ng/g dw in agricultural and industrial soils, respectively. C10Cl5-10 SCCPs and C14-15Cl5-7 MCCPs were the predominant homologues in all samples. Analysis of the soil vertical profiles revealed that MCCP concentrations decreased significantly with depth (P < 0.01). SCCPs more efficiently penetrated into the soils than MCCPs because of their higher water solubility and less octanol-water partition coefficient (Kow) values. A preliminary risk assessment suggested no potential health risks caused by non-dietary exposure. The daily exposure doses of CPs via ingestion were significantly (P < 0.01) higher for children (5.41 ± 2.11 × 10-3 and 1.68 ± 1.03 × 10-2 µg kg-1 day-1) and adults (2.56 ± 0.99 × 10-4 and 7.94 ± 4.87 × 10-4 µg kg-1 day-1) than dermal permeation exposure. Furthermore, CPs at current levels posed low ecological risks (0.1 ≤ RQ < 1) according to the risk quotient model. This study enhanced our understanding of the fates and behaviors of CPs in the terrestrial environment.

Polymeric Nanogel for Oral Delivery of the Chemotherapeutic Agent: Fabrication and Evaluation Alongside Toxicological Studies and Histopathological Examination.

Nanogel has attracted considerable attention as one of the most versatile drug delivery systems, especially for site-specific and/or time-controlled delivery of the chemotherapeutic agent. The main objective of this study was to prepare the polymeric nanogel characterized by Fourier transform infrared spectroscopy, x-ray diffraction, thermogravimetric analysis, differential scanning, and oral acute toxicity. Free radical polymerization was done for the fabrication of polymeric nanogel. Fourier transform infrared spectroscopy was used to confirm the successful free radical polymerization. Various techniques such as x-ray diffraction, differential scanning calorimetric, and thermogravimetric analysis measurement were used to investigate the thermal behavior and crystallinity of developed nanogel. Parameters such as swelling, drug loading, and in vitro drug release is enhanced as polymers and monomers concentrations increase while these parameters decrease in case of increasing crosslinker concentration. The oral biocompatibility results of developed nanogel exhibited no toxicity in rabbits. Histopathological changes were observed between empty and loaded group. The nanosized gel offers a specific surface area which increases the stability of loaded drug (oxaliplatin) and bioavailability of the drug (oxaliplatin) as compared to the conventional drug delivery systems.

Etiological study of short stature in children and role of insulin like growth factor-1 and insulin like growth factor binding protein-3 as screening markers for growth hormone deficiency.

OBJECTIVE: To determine aetiological factors in children with short stature, and to evaluate the role of insulin like growth factor-1 and insulin like growth factor binding protein-3 as screening markers for growth hormone deficiency. METHODS: The cross-sectional study was conducted at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from August 2020 to July 2021, and comprised children with short stature. Evaluation protocol included complete history and examination, baseline laboratory investigations, X-ray for bone age and karyotyping. Growth hormone status was assessed using growth hormone stimulation tests, and serum insulin like growth factor-1 and insulin like growth factor binding protein-3 levels were also assessed. Data was analysed using SPSS 25. RESULTS: Of the 649 children, 422(65.9%) were boys and 227(34.9%) were girls. The overall median age was 11 years (interquartile range: 11 years). Of the total, 116(17.9%) children had growth hormone deficiency. Familial short stature was present in 130(20%) children and constitutional delay in growth and puberty in 104(16.1%). There was no significant difference in levels of serum insulin like growth factor-1 and insulin like growth factor binding protein-3 in children who had growth hormone deficiency and those who had other causes of short stature (p>0.05). CONCLUSIONS: Physiological variants of short stature were found to be more common in the population followed by growth hormone deficiency. Serum insulin like growth factor-1 and insulin like growth factor binding protein-3 levels alone should not be used to screen children with short stature for growth hormone deficiency.

Association of Pro-Inflammatory Cytokines with Vitamin D in Hashimoto's Thyroid Autoimmune Disease.

Background and objectives: Hashimoto's thyroiditis is an important autoimmune thyroid condition. It is characterized by lymphocytic congestion of the thyroid gland followed by progressive deterioration and fibrous substitution of the thyroid in the parenchymal structure. This study has provided insight into the variations of blood pro-inflammatory cytokine levels in patients with Hashimoto's disease and the key role of vitamin D levels among selected patients. Materials and Methods: A total of 144 participants including healthy controls and patients were studied in the current study in which 118 were female and 26 were male. The thyroid profile was evaluated in patients with Hashimoto's thyroiditis and healthy controls. Results: The mean ± SD Free T4 in the patients was recorded as 14.0 ± 4.9 pg/mL, and TSH was 7.6 ± 2.5 IU/L, whereas the median ± IQR thyroglobulin antibodies (anti-TG) were 285 ± 142. Thyroid peroxidase antibodies (anti-TPO) were 160 ± 63.5, whereas in the healthy controls, the mean ± SD Free T4 was recorded as 17.2 ± 2.1 pg/mL, and TSH was 2.1 ± 1.4 IU/L, whereas the median ± IQR anti-TGs were 56.30 ± 46.06, and anti-TPO was 5.6 ± 5.12. The assessment of pro-inflammatory cytokines (pg/mL) and total Vitamin D levels (nmol/L) in patients with Hashimoto's thyroiditis was recorded with values IL-1B 6.2 ± 0.8, IL-6 9.4 ± 0.4, IL-8 7.5 ± 0.5, IL-10 4.3 ± 0.1, IL-12 3.8 ± 0.5, TNF-α 7.6 ± 1.1, and total vitamin D 21.89 ± 3.5, whereas in healthy controls the mean ± SD IL-1B was 0.6 ± 0.1, IL-6 2.6 ± 0.5, IL-8 3.0 ± 1.2, IL-10 3.3 ± 1.3, IL-12 3.4 ± 0.4, TNF-α 1.4 ± 0.3 and total vitamin D was 42.26 ± 5.5. Conclusions: It was found that individuals with Hashimoto's thyroiditis had raised serum levels of IL-1B, IL-6, IL-8, IL-10, IL-12, and TNF-α as compared to the healthy controls, whereas the total vitamin D levels were remarkably low as compared to health controls. Serum TSH, anti-TG, and anti-TPO levels were typically lower in controls and much higher in individuals with Hashimoto's thyroiditis. The current study's findings might aid in future studies and in the diagnosis and management of autoimmune thyroid disease.

Pharmacoepidemiological evaluation of off label and unlicensed prescription in pediatric intensive care units at tertiary care hospitals of Peshawar, Pakistan.

Population of pediatric intensive care units are at high risk of receiving off label and unlicensed drug use. Little is known about the characteristics and prevalence of unlicensed and off label prescriptions in pediatric intensive care units (PICUs) at tertiary care settings of Pakistan. Case notes of 420 children were reviewed for unlicensed and off label prescriptions during the one year. Medication profiles were assessed using Micromedex. Logistic regression was applied to calculate the odds-ratios for predictors of unlicensed and off label prescriptions. of the total prescriptions, 29.8% prescriptions were unlicensed from FDA and 42.27% prescriptions were off labelled. Dose (32.79%) was the most common reason for off label prescriptions followed by the indication (26.13%) and indication-dose (13.98%). Multivariate regression analysis revealed no significant association between the unlicensed prescriptions with their predictors. In reference to corresponding category, prescribed medications less than 5 (OR 0.280, 95%CL 0.137-0.570) were significantly less likely to receive off label prescriptions as compared to patients received 6 or more medications. Substantial numbers of children are exposed to unlicensed and off label prescriptions. Standards of drug quality, safety and efficacy should apply equally in adults and in pediatrics under ethical perspective. Suitable clinical interventions must be established by drug manufactures and government agencies for improved pediatric pharmacotherapy.

A novel method development and validation for determination of 2,4,6-Trinitrotoluene and its metabolites on LC-MS/MS.

LC-MS/MS has recently emerged as the best practice for simultaneous analysis of 2, 4, 6 Trinitrotoluene (TNT) and its metabolites. We have developed and validated an LC-MS/MS method for simultaneous quantification of 2, 4, 6 Trinitrotoluene (TNT) and its metabolites 4-ADNT, 2-ADNT, 2,4-DNT, and 2,6-DNT in urine samples. These four metabolites were acid hydrolyzed using 1 mL of urine followed by extraction using n-Hexane and ethyl acetate as an extracting solvent. Separation was achieved by centrifugation, and the supernatant was dried under nitrogen, reconstituted with water and acetonitrile, and then filtered. Chromatographic separation was achieved on Agilent Poroshel 120 EC-C18 column (2.1 mm × 75 mm × 2.7 µm) utilizing two mobile phases 0.1% formic acid in water and 0.1% formic acid in acetonitrile in gradient flow. The validated AMR of TNT and its metabolites was 7.8-1000 ng/mL. The method showed an excellent correlation (>0.99) for TNT and its metabolites. Accuracy and within/between day precision of TNT and its metabolites were within ±15%. The integrity of diluted samples was maintained for each dilution factor. The method was found stable after storage and freeze-thaw cycle. The presented method can be used for TNT screening in occupationally exposed ordnance factory workers.

Fundamentals of Hysteresis in Perovskite Solar Cells: From Structure-Property Relationship to Neoteric Breakthroughs.

Perovskite solar cells (PSC) have shown a rapid increase in efficiency than other photovoltaic technology. Despite its success in terms of efficiency, this technology is inundated with numerous challenges hindering the progress towards commercial viability. The crucial one is the anomalous hysteresis observed in the photocurrent density-voltage (J-V) response in PSC. The hysteresis phenomenon in the solar cell presents a challenge for determining the accurate power conversion efficiency of the device. A detailed investigation of the fundamental origin of hysteresis behavior in the device and its associated mechanisms is highly crucial. Though numerous theories have been proposed to explain the causes of hysteresis, its origin includes slow transient capacitive current, trapping, and de-trapping process, ion migrations, and ferroelectric polarization. The remaining issues and future research required toward the understanding of hysteresis in PSC device is also discussed.

Co-Combination of Pregabalin and Withaniacoagulans-Extract-Loaded Topical Gel Alleviates Allodynia and Hyperalgesia in the Chronic Sciatic Nerve Constriction Injury for Neuropathic Pain in Animal Model.

The current study reports the fabrication of co-combination gel using Pregabalin and Withania coagulans fruit extract to validate its effectiveness for neuropathic pain in chronic constriction injury (CCI) rat models. Three topical gels were prepared using Carbopol 934 through a pseudo-ternary phase diagram incorporating the Pregabalin (2.5%), Withania coagulans extract (2%), and co-combination of both Pregabalin (2.5%) and Withania coagulans extract (2%). Gels were characterized. FTIR showed a successful polymeric network of the gel without any interaction. The drug distribution at the molecular level was confirmed by XRD. The AFM images topographically indicated the rough surface of gels with a size range from 0.25 to 330 nm. DSC showed the disappearance of sharp peaks of the drug and extract, showing successful incorporation into the polymeric network of gels. The in vitro drug release of co-combination gel was 73% over 48 h. The mechanism of drug release by combination gel was Higuchi+ fickian with values of n (0.282) and R2 (0.947). An in vivo study for pain assessment via four methods: (i) heat hyperalgesia, (ii) cold allodynia, (iii) mechano-hyperalgesia, and (iv) dynamic mechano-allodynia, confirmed that topical treatment with co-combination gel reduced the pain significantly as indicated by the p value: R1 (p < 0.001), R2 (p < 0.001), R3 (p < 0.015), and R4 (p < 0.0344). The significance order was R2 (****) > R1 (***) > R3 (**) > R4 (*) > R5 (ns).

Integrated System Pharmacology Approaches to Elucidate Multi-Target Mechanism of Solanum surattense against Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant liver tumors with high mortality. Chronic hepatitis B and C viruses, aflatoxins, and alcohol are among the most common causes of hepatocellular carcinoma. The limited reported data and multiple spectra of pathophysiological mechanisms of HCC make it a challenging task and a serious economic burden in health care management. Solanum surattense (S. surattense) is the herbal plant used in many regions of Asia to treat many disorders including various types of cancer. Previous in vitro studies revealed the medicinal importance of S. surattense against hepatocellular carcinoma. However, the exact molecular mechanism of S. surattense against HCC still remains unclear. In vitro and in silico experiments were performed to find the molecular mechanism of S. surattense against HCC. In this study, the network pharmacology approach was used, through which multi-targeted mechanisms of S. surattense were explored against HCC. Active ingredients and potential targets of S. surattense found in HCC were figured out. Furthermore, the molecular docking technique was employed for the validation of the successful activity of bioactive constituents against potential genes of HCC. The present study investigated the active "constituent-target-pathway" networks and determined the tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), mammalian target of rapamycin (mTOR), Bcl-2-like protein 1(BCL2L1), estrogen receptor (ER), GTPase HRas, hypoxia-inducible factor 1-alpha (HIF1-α), Harvey Rat sarcoma virus, also known as transforming protein p21 (HRAS), and AKT Serine/Threonine Kinase 1 (AKT1), and found that the genes were influenced by active ingredients of S. surattense. In vitro analysis was also performed to check the anti-cancerous activity of S. surattense on human liver cells. The result showed that S. surattense appeared to act on HCC via modulating different molecular functions, many biological processes, and potential targets implicated in 11 different pathways. Furthermore, molecular docking was employed to validate the successful activity of the active compounds against potential targets. The results showed that quercetin was successfully docked to inhibit the potential targets of HCC. This study indicates that active constituents of S. surattense and their therapeutic targets are responsible for their pharmacological activities and possible molecular mechanisms for treating HCC. Lastly, it is concluded that active compounds of S. surattense act on potential genes along with their influencing pathways to give a network analysis in system pharmacology, which has a vital role in the development and utilization of drugs. The current study lays a framework for further experimental research and widens the clinical usage of S. surattense.

Extraction of Bioactive Compounds for Antioxidant, Antimicrobial, and Antidiabetic Applications.

This study was designed to check the potential of secondary metabolites of the selected plants; Citrullus colocynthis, Solanum nigrum, Solanum surattense, Calotropis procera, Agave americana, and Anagallis arvensis for antioxidant, antibacterial, antifungal, and antidiabetic agents. Plant material was soaked in ethanol/methanol to get the crude extract, which was further partitioned via solvent extraction technique. GCMS and FTIR analytical techniques were applied to check the compounds responsible for causing antioxidant, antimicrobial, and antidiabetic activities. It was concluded that about 80% of studied extracts/fractions were active against α-amylase, ranging from 43 to 96%. The highest activity (96.63%) was exhibited by butanol fractions of A. arvensis while the least response (43.65%) was shown by the aqueous fraction of C. colocynthis and the methanol fraction of fruit of S. surattense. The highest antioxidant activity was shown by the ethyl acetate fraction of Anagallis arvensis (78.1%), while aqueous as well as n-hexane fractions are the least active throughout the assay. Results showed that all tested plants can be an excellent source of natural products with potential antimicrobial, antioxidant, and antidiabetic potential. The biological response of these species is depicted as a good therapeutic agent, and, in the future, it can be encapsulated for drug discovery.

Assessment of National External Quality Assurance Programme of Pakistan as a tool for improving quality of lab results among participating laboratories.

OBJECTIVE: To assess the impact of the National External Quality Assessment Programme of Pakistan NEQAPP in improving the quality of laboratory results among the participating laboratories. METHODS: The cross-sectional observational study was conducted from July to December 2020 at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, in association with the National Quality Assurance Programme of Pakistan. A survey questionnaire was developed and sent to the participating laboratories via email. Frequencies of their responses were calculated and data was analysed using SPSS 21. RESULTS: Of the 150 laboratories approached, 145(96.6%) responded. Among them, 140 (96.6%) laboratories were satisfied by the information provided on the programme's portal, 123(84.8%s) were pleased with the responsiveness of the programme manager, 140(96.6%) reported quality of services had improved after participation in the programme, 129(89%) indicated that the clinician's confidence had enhanced, and 122(84%) said the participation in the programme had improved the credibility of their respective of laboratories. CONCLUSIONS: The National External Quality Assessment Programme of Pakistan was found to have significantly contributed in improving the quality of laboratory results among the participating laboratories.

A case of congenital methaemoglobinaemia with secondary polycythemia.

Haemoglobin contains iron in a ferrous form. When the iron is oxidized, it is called Methaemoglobin (MetHb). MetHb leads to tissue hypoxia, cyanosis, and secondary polycythemia. Methaemoglobinaemia is acquired or congenital. In this case, a 22-years-old male patient presented with cyanosis, headache, and lack of concentration. Cyanosis was present since birth. His previous investigations showed polycythemia. He was misdiagnosed on multiple occasions and was undergoing venesections for polycythemia. On evaluation at a private clinic, an Oxygen saturation gap was noted between the results of the pulse oximeter and arterial blood gas analyzer. This raised suspicion on the presence of MetHb. He was referred to Armed Forces Institute of Pathology, Rawalpindi for further workup.The sample obtained for MetHb was chocolate brown in colour. Analysis was done via co-oximetry. A high level of MetHb (45.6%) was obtained. All other radiological and haematological investigations were in the normal range. On the basis of history, clinical presentation, and investigations, he was diagnosed as a case of congenital methaemoglobinaemia with secondary polycythemia.

Establishing biotinidase reference interval: A foundation stone for newborn screening of biotinidase deficiency in Pakistan.

OBJECTIVE: To determine the reference interval of biotinidase activity in healthy neonates. METHODS: The cross-sectional study was conducted at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from May to November 2019, and comprised blood samples collected from healthy neonates aged 2-6 days. The samples were collected on filter paper and analysed on genetic screening processor based on dissociation-enhanced lanthanide flouroimmunoassay. Data was analysed using SPSS 21. RESULTS: Of the 120 dried blood spot specimens, 81(67.5%) were from male babies and 39(32.5%) from female babies. Reference interval for biotinidase activity, based on 2.5th and 97.5th percentiles, was from 3.0 to 11.0 nmol/ml/min. CONCLUSIONS: Screening of newborns for biotinidase deficiency is crucial to prevent irreversible neurological damage.