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Liver and Breast cancer are ranked as the most prevailing cancers that cause high cancer-related mortality. As cancer is a life-threatening disease that affects the human population globally, there is a need to develop novel therapies. Among the available treatment options include radiotherapy, chemotherapy, surgery, and immunotherapy. The most superlative modern method is the use of plant-derived anticancer drugs that target the cancerous cells and inhibit their proliferation. Plant-derived compounds are generally considered safer than synthetic drugs/traditional therapies and could serve as potential novel targets to treat liver and breast cancer to revolutionize cancer treatment. Alkaloids and Polyphenols have been shown to act as anticancer agents through molecular approaches. They disrupt various cellular mechanisms, inhibit the production of cyclins and CDKs to arrest the cell cycle, and activate the DNA repairing mechanism by upregulating p53, p21, and p38 expression. In severe cases, when no repair is possible, they induce apoptosis in liver and breast cancer cells by activating caspase-3, 8, and 9 and increasing the Bax/Bcl-2 ratio. They also deactivate several signaling pathways, such as PI3K/AKT/mTOR, STAT3, NF-kB, Shh, MAPK/ERK, and Wnt/β-catenin pathways, to control cancer cell progression and metastasis. The highlights of this review are the regulation of specific protein expressions that are crucial in cancer, such as in HER2 over-expressing breast cancer cells; alkaloids and polyphenols have been reported to reduce HER2 as well as MMP expression. This study reviewed more than 40 of the plant-based alkaloids and polyphenols with specific molecular targets against liver and breast cancer. Among them, Oxymatrine, Hirsutine, Piperine, Solamargine, and Brucine are currently under clinical trials by qualifying as potent anticancer agents due to lesser side effects. As a lot of research is there on anticancer compounds, there is a desideratum to compile data to move towards clinical trials phase 4 and control the prevalence of liver and breast cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Heavy metal pollution is a global issue. Current study provides evidence on Pb toxicity ameliorative potential and safe nature of Levilactobacillus brevis MZ384011 (S1) and Levilactobacillus brevis MW362779 (S2), isolated from carnivore gut and human milk, respectively. In a 60-days experiment, the rats were distributed into six groups. G-I, G-V and G-VI were kept on normal diet, while GII-IV were fed on lead nitrate (500 mg/kg) supplemented food, throughout experiment. After confirmation of Pb toxicity in GII-IV at 15th day, S1 was orally administered to G-III and G-V while S2 was given to G-IV and G-VI at a dose of 1 × 10 9 CFU/animal/day. On day 60 of experiment, positive control (G-II) displayed significant reduction in body weight, total protein, albumin, globulin, mineral profile, erythrocyte count, hemoglobin, hematocrit and hematological indices and elevation in leukocyte count, alanine aminotransferase, aspartate aminotransferase, bilirubin, uric acid and creatinine along with alterations in hepato-renal architecture. With reference to G-II, the G-III and G-IV displayed significant improvement in all aforementioned parameters, 40-60% reduction in tissue Pb levels (blood, liver, kidney and adipose tissue) and elevation in fecal Pb contents (p = 0.000). The groups V and VI did not show any sign of toxicity. The findings confirm that strains are safe for biological application and can reverse Pb toxicity by facilitating fecal Pb excretion and reducing its systemic dispersal. To best of our information this is the first report on Pb toxicity ameliorative role of Levilactobacillus brevis from human milk, the safest source., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background and Objective: Pain assessment plays a vital role in the management of patients across various healthcare settings. Accurate and reliable pain evaluation tools are essential for effective pain management and improving patient outcomes. The objective of this study was to assess ease of Full Cup Test (FCT) as a pain scale and to compare use of FCT with Visual Analogue Scale (VAS) for pain evaluation., Methods: A cross-sectional study carried out at a tertiary care hospital from December 2021 to July 2022 on individuals with pain at various body locations. Pain severity was evaluated using two pain assessment tools, the FCT and the VAS. The main objectives of the study were to assess correlation and agreement between the FCT and VAS; using Kappa statistics., Results: Of the total 288 subjects, median age was 42.5 years (IQR: 13-78), and median duration of pain was four months (IQR: one day to forty years). Analysis revealed significant positive correlation (r=0.577) between the Full Cup Test (FCT) and the Visual Analog Scale (VAS), indicating a relationship between both pain assessment tools. Significant agreement was also observed between FCT and VAS, with a kappa value of 0.596 (p<0.0001). Results however indicated that illiterate patients found it easier to understand FCT compared to VAS., Conclusion: The Full Cup Test (FCT) emerged as a potentially valuable tool for assessing pain severity in a diverse range of patients. Regardless of age, gender, education level, and ethnicity, FCT demonstrated utility with ease in detecting pain severity., Competing Interests: Conflict of interests: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Lead (Pb) is a substantial contaminant in the environment and a potent toxin for living organisms. Current study describes probiotic characteristics of Pb-biosorbing lactic acid bacteria (LAB), and response surface methodology (RSM) based optimization of physical conditions for maximum Pb biosorption. A total of 18 LAB, isolated from carnivore feces (n = 8) and human breast milk (n = 9), along with one reference strain Lactobacillus acidophilus  ATCC4356 were included in the study. Pb biosorption was strain specific. Eight strains, demonstrating ≥ 70 % lead biosorption, were selected for further testing. The lactobacillus-Pb complex was found to be stable and strains had a negative surface charge. The strains displayed good probiotic properties with the survival rate of 71-90 % in simulated gastric environment, 36-69 % in intestinal condition (1.8 % bile salts) and 55-72 % hydrophobicity. On the basis of excellent probiotic ability, Levilactobacillus brevis  MZ384011 and  Levilactobacillus brevis  MW362779 were selected for optimization of physical conditions of Pb biosorption through RSM. Maximum biosorption was observed at pH 6 in 60 min at a cell density of 1 g/L. L. brevis  MZ384011 and  L. brevis  MW362779 are recommended for experimentation on Pb toxicity amelioration and safety evaluation in  in-vivo  setting., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

The markedly low oral bioavailability of domperidone (anti-emetic drug) is associated with rapid first-pass metabolism in the intestine and liver. To counteract such affects, there is a need to devise a strategy to enhance absorption and subsequently bioavailability. Thus, the current study was aimed at synthesizing phytosomes consisting of phosphatidylcholine and piperine (a P-glycoprotein inhibitor). Phytosomes were prepared by salting-out method. The developed phytosomes were extensively characterized for size, zeta potential, polydispersity index, entrapment efficiency (EE %), infra-red spectroscopy, X-ray diffraction , in vitro drug release, ex vivo permeation, in vivo pharmacokinetic and toxicity. The engineered formulations of phytosomes with piperine exhibited a significant improvement in oral bioavailability of domperidone (79.5%) in comparison with the pure drug suspension under the same conditions. Pharmacokinetic parameters such as maximal plasma concentration (C max ) and the plasma concentration (estimated from area under the curve; AUC) of domperidone have been greatly increased relative to drug alone. The improved drug absorption was attributed to inhibition of P-glycoprotein transporter. The findings of current research work suggest that the optimized phytosomes based drug delivery containing phytochemicals as bioenhancers have the potential to improve bioavailability of poorly bioavailable drugs that are substrate to P-glycoprotein.

Diabetes being a chronic metabolic disorder have attracted the attention of medicinal chemists and biologists. The introduction of new and potential drug candidates for the cure and treatment of diabetes has become a major concern due to its increased prevelance worldwide. In the current study, twenty-seven azachalcone derivatives 3-29 were synthesized and evaluated for their antihyperglycemic activities by inhibiting α-amylase and α-glucosidase enzymes. Five compounds 3 (IC 50  = 23.08 ± 0.03 µM), (IC 50  = 26.08 ± 0.43 µM), 5 (IC 50  = 24.57 ± 0.07 µM), (IC 50  = 27.57 ± 0.07 µM), 6 (IC 50  = 24.94 ± 0.12 µM), (IC 50  = 27.13 ± 0.08 µM), 16 (IC 50  = 27.57 ± 0.07 µM), (IC 50  = 29.13 ± 0.18 µM), and 28 (IC 50  = 26.94 ± 0.12 µM) (IC 50  = 27.99 ± 0.09 µM) demonstrated good inhibitory activities against α-amylase and α-glucosidase enzymes, respectively. Acarbose was used as the standard in this study. Structure-activity relationship was established by considering the parent skeleton and different substitutions on aryl ring. The compounds were also subjected for kinetic studies to study their mechanism of action and they showed competitive mode of inhibition against both enzymes. The molecular docking studies have supported the results and showed that these compounds have been involved in various binding interactions within the active site of enzyme., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ranunculus muricatus L. is a spiny fruit buttercup that is used in various traditional medicinal systems. In the current investigation of R. muricatus , the new chalcone 4-benzyloxylonchocarpin ( 1 ), the new anthraquinone muracatanes A ( 2 ), the new-to-nature anthraquinone muracatanes B ( 3 ), and the new naphthalene analog muracatanes C ( 4 ) were isolated, in addition to the three previously reported compounds, 4-methoxylonchocarpin ( 5 ), β-sitosterol ( 6 ), and β-sitosterol β-D-glucopyranoside ( 7 ). Their structures were elucidated using 1D ( 1 H and 13 C) and 2D (COSY, HSQC, and HMBC) NMR spectroscopy and HR-ESI-MS. Chalcone 1 showed potent acetylcholinesterase inhibitory effects with K i of 5.39 µM and K i' of 3.54 µM, but none of the isolated compounds showed inhibitory activity towards butyrylcholinesterase. Anthraquinone 3 illustrated α-glucosidase inhibitory effects with IC 50 -values of 164.46 ± 83.04 µM. Compound 5 displayed moderate cytotoxic activity towards ovarian carcinoma (A2780, IC 50 = 25.4 µM), colorectal adenocarcinoma (HT29, IC 50 = 20.2 µM), breast cancer (MCF7, IC 50 = 23.7 µM), and thyroid carcinoma (SW1736, IC 50 = 26.2 µM) while it was inactive towards pharynx carcinoma (FaDu: IC 50 > 30 µM).

Although ebastine (EBT) can impede histamine-induced skin allergic reaction and persuade long acting selective H1 receptor antagonistic effects but its poor water solubility circumscribed its clinical application. The main objective of this research work was to improve the aqueous solubility and oral bioavailability of EBT by preparing EBT-loaded bilosomes (EBT-PC-SDC-BS). A thin film hydration method was used to prepare ebastine loaded bilosomes. The prepared-formulations were optimized considering size, morphology and entrapment efficiency. The SEM images revealed regular and spherical shape of bilosomes. Average size of the prepared EBT-PC-SDC-BS was 665.8 nm and zeta potential was around-32.9 mV with 89.05 % average entrapment efficiency (EE).Importantly, the solubility of EBT in water was amplified up to 17.9 μg/ml compared to pure drug (2 μg/mL) reflecting a highest solubility increase of 751 %. In vitro drug release results of prepared EBT-PC-SDC-BS exhibited improved release behavior. Finally, it is established from the results that the EBT-PC-SDC-BS could function as a favorable nano-carrier system to improve the solubility as well as dissolution of EBT.

Objective: To determine the frequency of isolation of coagulase-negative staphylococci and their resistance to methicillin over a period of time., Methods: The descriptive cross-sectional study was carried out at Army Medical College, Rawalpindi, from June 2009 to May 2012, and comprised clinical samples mostly from patients admitted to the intensive care unit. They were inoculated onto appropriate culture media depending upon the specimen. After 24-hour incubation at 35°C, coagulase-negative staphylococci were identified on the basis of colony morphology, gram staining, a positive catalase and a negative tube coagulase test.Methicillin resistance among the isolated staphylococci was determined using a 30µg Cefoxitin disc as per the Clinical and Laboratory Standards Institute protocol. Number of coagulase-negative staphylococci for each year and their methicillin resistance rates were calculated. A comparison was made with methicillin resistant staphylococcus aureus) isolated during the same period., Results: Of the total 1331 specimens studies over three years, 581(43.65%) were coagulase-negative staphylococci. The rate of coagulase-negative staphylococci and methicillin resistance was higher each year; 110(26.6%) in May 2009-Jun 2010, 134(36.5%) in 2011, and 337(61%) in 2012. Methicillin resistance rates also increased from 25(22.7%) to 46(34.3%) and then to 201(59.6%) in 2012.Maximum isolated specimens came from blood 311(53.5%), followed by pus/swabs 204(35.1%)., Conclusions: The frequency of isolation of coagulase-negative staphylococci and its methicillin resistance among hospitalised patients is on the rise.

Fungi are considered good producers of industrially valuable enzymes with higher enzymatic activities. Among these cellulases are group of extracellular enzymes commonly employed in many industries for the hydrolysis of cellulolytic material. Aspergillus fumigatus produced exoglucanase having high enzymatic activity (83 U/gds) during the solid-state fermentation of wheat straw under optimum physical and nutritional conditions. Maximum production was obtained after 72 h of fermentation, at 55 °C temperature, pH 5.5, 80 % moisture level, and 2 mL fungal inoculum. Production was further increased by the addition of fructose (0.3 %) as additional carbon source, peptone (0.4 %) as nitrogen source, Tween-80 (0.3 %) as surfactant, and ammonium sulfate (0.2 %) in media. Exoglucanase was 2.30-folds purified by adding 40 % ammonium sulfate with volumetric activity 95.4 U/gds and specific activity 14.74 U/mg. Further, it was 5.18-folds purified by gel filtration chromatography with volumetric activity 115.2 U/gds and specific activity 33.10 U/mg. Purified exoglucanase has maximum activity at 55 °C and pH 4.8 using 1 % Avicel aqueous solution as substrate. The K(m) and V(max) were 4.34 mM and 7.29 μM/min, respectively. Calcium, magnesium, and zinc ions have positive effect on exoglucanase activity.