Assessment of total aflatoxin and ochratoxin A in poultry feed ingredients by thin-layer chromatography and enzyme-linked immunosorbent assay.

Objective: This study was conducted to evaluate the prevalence of total aflatoxin (AF) and ochratoxin A (OTA) in poultry feed ingredients under different environmental conditions during the summer and winter seasons, while the hygiene quality of the feed ingredient was assessed through viable fungal count (VFC). Materials and Methods: A total of 288 poultry feed ingredients (n = 96 each) samples were collected from different poultry shops, which were initially analyzed for the presence of AF and OTA through thin layer chromatography (TLC) and then confirmed the contamination concentration through the enzyme-linked immunosorbent assay method. Results: The results of the current study confirmed the incidence of contamination with AF and OTA by TLC and ELISA methods. The contamination level of AF ranged from 26.09 to 50.56 (mean = 41.22 ± 9.45) µg/kg, whereas the contamination level of OTA ranged from 50.13 to 6.21 (mean 42.60 ± 6.21) µg/kg. The contamination level of AF was found to be above the permissible level set by the Food and Drug Administration (20 µg/kg), whereas the contamination level of OTA was below the permissible limits. Moreover, the VFC values were also below the recommended level. The results showed that the association between AF, OTA, and moisture content was significant (p < 0.05). Conclusion: Mycotoxin contamination was significantly (p < 0.05) highest in the winter season. These findings suggested that continuous monitoring regimes might prevent mycotoxin contamination in poultry feed ingredients.

Ultrasensitive Near-Infrared Polarization Photodetectors with Violet Phosphorus/InSe van der Waals Heterostructures.

Near-infrared (NIR) polarization photodetectors with two-dimensional (2D) semiconductors and their van der Waals (vdW) heterostructures have presented great impact for the development of a wide range of technologies, such as in the optoelectronics and communication fields. Nevertheless, the lack of a photogenerated charge carrier at the device's interface leads to a poor charge carrier collection efficiency and a low linear dichroism ratio, hindering the achievement of high-performance optoelectronic devices with multifunctionalities. Herein, we present a type-II violet phosphorus (VP)/InSe vdW heterostructure that is predicted via density functional theory calculation and confirmed by Kelvin probe force microscopy. Benefiting from the type-II band alignment, the VP/InSe vdW heterostructure-based photodetector achieves excellent photodetection performance such as a responsivity (R) of 182.8 A/W, a detectivity (D*) of 7.86 × 1012 Jones, and an external quantum efficiency (EQE) of 11,939% under a 1064 nm photon excitation. Furthermore, the photodetection performance can be enhanced by manipulating the device geometry by inserting a few layers of graphene between the VP and InSe (VP/Gr/InSe). Remarkably, the VP/Gr/InSe vdW heterostructure shows a competitive polarization sensitivity of 2.59 at 1064 nm and can be integrated as an image sensor. This work demonstrates that VP/InSe and VP/Gr/InSe vdW heterostructures will be effective for promising integrated NIR optoelectronics.

Platinum-based targeted chemotherapies and reversal of cisplatin resistance in non-small cell lung cancer (NSCLC).

Lung cancer is the one of the most prevalent cancer in the world. It kills more people from cancer than any other cause and is especially common in underdeveloped nations. With 1.2 million instances, it is also the most prevalent cancer in men worldwide, making about 16.7% of the total cancer burden. Surgery is the main form of curative treatment for early-stage lung cancer. However, the majority of patients had incurable advanced non-small cell lung cancer (NSCLC) recurrence after curative purpose surgery, which is indicative of the aggressiveness of the illness and the dismal outlook. The gold standard of treatment for NSCLC patients includes drug targeting of specific mutated genes drive in development of lung cancer. Furthermore, patients with advanced NSCLC and those with early-stage illness needing adjuvant therapy should use cisplatin as it is the more active platinum drug. So, this review encompasses the non-small cell lung cancer microenvironment, treatment approaches, and use of cisplatin as a first-line regimen for NSCLC, its mechanism of action, cisplatin resistance in NSCLC and also the prevention strategies to revert the drug resistance.

Silica-Based Superhydrophobic and Superoleophilic Cotton Fabric with Enhanced Self-Cleaning Properties for Oil-Water Separation and Methylene Blue Degradation.

Superhydrophobic textiles with multifunctional characteristics are highly desired and have attracted tremendous research attention. This research employs a simple dip-coating method to obtain a fluorine-free silica-based superhydrophobic and superoleophilic cotton fabric. Pristine cotton fabric is coated with SiO2 nanoparticles and octadecylamine. SiO2 nanoparticles are anchored on the cotton fabric to increase surface roughness, and octadecyl amine lowers the surface energy, turning the hydrophilic cotton fabric into superhydrophobic. The designed cotton fabric exhibits a water contact angle of 159° and a sliding angle of 7°. The prepared cotton fabric is characterized by attenuated total reflectance-fourier transform infrared spectroscopy, X-ray diffraction, atomic force microscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. In addition, the coated fabric reveals excellent features, including mechanical and chemical stability, superhydrophobicity, superoleophilicity, and the self-cleaning ability. SiO2 nanoparticles and octadecylamine-coated cotton fabric demonstrate exceptional oil-water separation and wastewater remediation performance by degrading the methylene blue solution up to 89% under visible light. The oil-water separation ability is tested against five different oils with more than 90% separation efficiency. This strategy has the advantages of low-cost precursors, a simple and scalable coating method, enhanced superhydrophobicity and superoleophilicity, self-cleaning ability, efficient oil-water separation, and exceptional wastewater remediation performance.

Development, optimization and characterization of cisplatin loaded cubosomes for human lung carcinoma.

OBJECTIVES: This study aimed to develop, optimize and evaluate glyceryl monooleate (GMO) based cubosomes as a drug delivery system containing cisplatin for treatment of human lung carcinoma. SIGNIFICANCE: The significance of this research was to successfully incorporate slightly water soluble and potent anticancer drug (cisplatin) into cubosomes, which provide slow and sustained release of drug for longer period of time. METHODS: The delivery system was developed through top-down approach by melting GMO and poloxamer 407 (P407) at 70 °C and then drop-wise addition of warm deionized water (70 °C) containing cisplatin. The formulation then exposed to probe sonicator for about 2 min. A randomized regular two level full factorial design with help of Design Expert was used for optimization of blank cubosomal formulations. Cisplatin loaded cubosomes were then subjected to physico-chemical characterization. RESULTS: The characterization of the formulation revealed that it had a sufficient surface charge of -9.56 ± 1.33 mV, 168.25 ± 5.73 nm particle size, and 60.64 ± 0.11% encapsulation efficiency. The in vitro release of cisplatin from the cubosomes at pH 7.4 was observed to be sustained, with 94.5% of the drug being released in 30 h. In contrast, 99% of cisplatin was released from the drug solution in just 1.5 h. In vitro cytotoxicity assay was conducted on the human lung carcinoma NCI-H226 cell line, the cytotoxicity of cisplatin-loaded cubosomes was relative to that of pure cisplatin solution, while blank (without cisplatin) cubosomes were nontoxic. CONCLUSIONS: The obtained results demonstrated the successful development of cubosomes for sustained delivery of cisplatin.

Cubosomes were prepared, optimized, and evaluated for cisplatin delivery.A randomized regular two level full factorial design was constructed to optimize blank cubosomes.Blank cubosomes consisted of GMO as the lipid and P407 as an emulsifying agent.In vitro release studies demonstrated sustained release of cisplatin from cubosomes at pH 7.4.Cytotoxicity assay on human lung carcinoma cell line NCI-H226 showed similar cytotoxicity between cisplatin-loaded cubosomes and pure cisplatin solution while blank cubosomes exhibited no toxicity.

Direct differentiation of rat skin fibroblasts into cardiomyocytes.

Myocardial infarction (MI) is one of the major cardiovascular diseases caused by diminished supply of nutrients and oxygen to the heart due to obstruction of the coronary artery. Different treatment options are available for cardiac diseases, however, they do not completely repair the damage. Therefore, reprogramming terminally differentiated fibroblasts using transcription factors is a promising strategy to differentiate them into cardiac like cells in vitro and to increase functional cardiomyocytes and reduce fibrotic scar in vivo. In this study, skin fibroblasts were selected for reprogramming because they serve as a convenient source for the autologous cell therapy. Fibroblasts were isolated from skin of rat pups, propagated, and directly reprogrammed towards cardiac lineage. For reprogramming, two different approaches were adopted, i.e., cells were transfected with: (1) combination of cardiac transcription factors; GATA4, MEF2c, Nkx2.5 (GMN), and (2) combination of cardiac transcription factors; GATA4, MEF2c, Nkx2.5, and iPSC factors; Oct4, Klf4, Sox2 and cMyc (GMNO). After 72 h of transfection, cells were analyzed for the expression of cardiac markers at the mRNA and protein levels. For in vivo study, rat MI models were developed by ligating the left anterior descending coronary artery and the reprogrammed cells were transplanted in the infarcted heart. qPCR results showed that the reprogrammed cells exhibited significant upregulation of cardiac genes. Immunocytochemistry analysis further confirmed cardiomyogenic differentiation of the reprogrammed cells. For the assessment of cardiac function, animals were analyzed via echocardiography after 2 and 4 weeks of cell transplantation. Echocardiographic results showed that the hearts transplanted with the reprogrammed cells improved ejection fraction, fractional shortening, left ventricular internal systolic and diastolic dimensions, and end systolic and diastolic volumes. After 4 weeks of cell transplantation, heart tissues were harvested and processed for histology. The histological analysis showed that the reprogrammed cells improved wall thickness of left ventricle and reduced fibrosis significantly as compared to the control. It is concluded from the study that novel combination of cardiac transcription factors directly reprogrammed skin fibroblasts and differentiated them into cardiomyocytes. These differentiated cells showed cardiomyogenic characters in vitro, and reduced fibrosis and improved cardiac function in vivo. Furthermore, direct reprogramming of fibroblasts transfected with cardiac transcription factors showed better regeneration of the injured myocardium and improved cardiac function as compared to the indirect approach in which combination of cardiac and iPSC factors were used. The study after further optimization could be used as a better strategy for cell-based therapeutic approaches for cardiovascular diseases.

Hegemony of inflammation in atherosclerosis and coronary artery disease.

Inflammation drives coronary artery disease and atherosclerosis implications. Lipoprotein entry, retention, and oxidative modification cause endothelial damage, triggering innate and adaptive immune responses. Recruited immune cells orchestrate the early atherosclerotic lesions by releasing proinflammatory cytokines, expediting the foam cell formation, intraplaque haemorrhage, secretion of matrix-degrading enzymes, and lesion progression, eventually promoting coronary artery syndrome via various inflammatory cascades. In addition, soluble mediators disrupt the dynamic anti- and prothrombotic balance maintained by endothelial cells and pave the way for coronary artery disease such as angina pectoris. Recent studies have established a relationship between elevated levels of inflammatory markers, including C-reactive protein (CRP), interleukins (IL-6, IL-1ß), and tumour necrosis factor-alpha (TNF-α) with the severity of CAD and the possibility of future cardiovascular events. High-sensitivity C-reactive protein (hs-CRP) is a marker for assessing systemic inflammation and predicting the risk of developing CAD based on its peak plasma levels. Hence, understanding cross-talk interactions of inflammation, atherogenesis, and CAD is highly warranted to recalculate the risk factors that activate and propagate arterial lesions and devise therapeutic strategies accordingly. Cholesterol-inflammation lowering agents (statins), monoclonal antibodies targeting IL-1 and IL-6 (canakinumab and tocilizumab), disease-modifying antirheumatic drugs (methotrexate), sodium-glucose transport protein-2 (SGLT2) inhibitors, colchicine and xanthene oxidase inhibitor (allopurinol) have shown promising results in reducing inflammation, regressing atherogenic plaque and modifying the course of CAD. Here, we review the complex interplay between inflammatory, endothelial, smooth muscle and foam cells. Moreover, the putative role of inflammation in atherosclerotic CAD, underlying mechanisms and potential therapeutic implications are also discussed herein.

A dual-mode fluorescence and colorimetric sensing platform for efficient detection of ofloxacin in aquatic products using iron alkoxide nanozyme.

Trace detection of ofloxacin (OFL) with high sensitivity, reliability, and visual clarity is challenging. To address this, a novel dual-modal aptasensor with fluorescence-colorimetric capabilities was designed that exploit the target-induced release of 3,3',5,5'-tetramethylbenzidine (TMB) molecules from aptamer-gated mesoporous silica nanoparticles (MSNs), the oxidase-like activity of iron alkoxide (IA) nanozyme, and the fluorescence attributes of core-shell upconversion nanoparticles. Therefore, the study reports a dual mode detection, with a fluorescence detection range for OFL spanning from 0.1 µg/kg to 1000 µg/kg (and a detection limit of 0.048 µg/kg). Additionally, the colorimetric method offered a linear detection range of 0.3 µg/kg to 1000 µg/kg, with a detection limit of 0.165 µg/kg. The proposed biosensor had been successfully applied to the determination of OFL content in real samples with satisfactory recoveries (78.24-96.14 %).

Exploring the Interplay of the CRISPR-CAS System with Antibiotic Resistance in Staphylococcus aureus: A Poultry Meat Study from Lahore, Pakistan.

Staphylococcus aureus is one of the major pathogens responsible for causing food poisoning worldwide. The emergence of antibiotic resistance in this bacterium is influenced by various factors. Among them, bacterial acquired defense systems described as clustered regularly interspaced short palindromic repeats (CRISPR)-cas system might be involved in antibiotic resistance development in bacteria. The current study was designed to assess the prevalence of S. aureus and its antibiotic resistance profile and identify the relationship of the CRISPR-cas system with antimicrobial resistance, followed by phylogenetic analysis. Total samples (n = 188) of poultry meat were collected from the poultry bird market of Lahore, Punjab, Pakistan. We used both phenotypic (antibiotic disc diffusion) and genotypic methods (PCR) to identify multi-drug resistant (MDR) strains of S. aureus. Additionally, the role of the CRISPR-Cas system in the isolated MDR S. aureus was also assessed. In addition, real-time quantitative PCR (qRT-PCR) was used to evaluate the association of the CRISPR-cas system with antimicrobial resistance. All of the S. aureus isolates showed 100% resistance against erythromycin, 97.5% were resistant to tetracycline, and 75% were resistant to methicillin. Eleven isolates were MDR in the current study. The CRISPR system was found in all MDR isolates, and fifteen spacers were identified within the CRISPR locus. Furthermore, MDR S. aureus isolates and the standard strain showed higher expression levels of CRISPR-associated genes. The correlation of said system with MDR isolates points to foreign gene acquisition by horizontal transfer. Current knowledge could be utilized to tackle antibiotic-resistant bacteria, mainly S. aureus.

Serious Adverse Events of Inclisiran in Patients With Hypercholesterolemia, a Meta-Analysis of ORION Trials.

BACKGROUND: Several studies have been conducted over the years to find an effective and safe therapeutic agent to treat hypercholesterolemia. Inclisiran is a novel drug being studied for its efficacy and safety in reducing low-density lipoprotein cholesterol levels in patients to reduce the risk of cardiovascular diseases. No previous study was done to review the trials for the serious adverse events of this drug. The primary objective of this research is to investigate the incidence of serious adverse events of this drug. DESIGN: A systematic review and meta-analysis of clinical trials is performed. METHODS: A systematic search of PubMed, Embase, and ClinicalTrials.gov, from their inception till July 3, 2023, was performed for ORION trials, studying the efficacy and safety of inclisiran. The random-effects model was used in the meta-analysis to provide a pooled proportion of serious adverse events. The risk of bias in each study was assessed by the Cochrane Risk of Bias Tool. RESULTS: From 319 studies searched from the databases, only 8 relevant articles remained after a detailed evaluation. These studies, having a total of 4981 patients, were involved in the analysis, with a pooled estimate showing a nonsignificant incidence of serious adverse events. Each adverse event was studied individually, and product issues and endocrine disorders had the highest odds ratio among them. All included studies were classified as moderate quality. CONCLUSION: Following systematic review and meta-analysis, we found no significant differences in any serious adverse events following the administration of inclisiran. However, larger ongoing trials will provide additional data to evaluate the safety profile of this agent.

Neuroprotective Effects of N-methyl-(2S, 4R)-trans-4-hydroxy-L-proline (NMP) against Amyloid-ß-Induced Alzheimer's Disease Mouse Model.

Alzheimer's disease (AD), is a progressive neurodegenerative disorder that involves the deposition of ß-amyloid plaques and the clinical symptoms of confusion, memory loss, and cognitive dysfunction. Despite enormous progress in the field, no curative treatment is available. Therefore, the current study was designed to determine the neuroprotective effects of N-methyl-(2S, 4R)-Trans-4-hydroxy-L-proline (NMP) obtained from Sideroxylon obtusifolium, a Brazilian folk medicine with anti-inflammatory and anti-oxidative properties. Here, for the first time, we explored the neuroprotective role of NMP in the Aß1-42-injected mouse model of AD. After acclimatization, a single intracerebroventricular injection of Aß1-42 (5 µL/5 min/mouse) in C57BL/6N mice induced significant amyloidogenesis, reactive gliosis, oxidative stress, neuroinflammation, and synaptic and memory deficits. However, an intraperitoneal injection of NMP at a dose of (50 mg/kg/day) for three consecutive weeks remarkably decreased beta secretase1 (BACE-1) and Aß, activated the astrocyte and microglia expression level as well as downstream inflammatory mediators such as pNF-ĸB, TNF-α, and IL-1ß. NPM also strongly attenuated oxidative stress, as evaluated by the expression level of NRF2/HO-1, and synaptic failure, by improving the level of both the presynaptic (SNAP-25 and SYN) and postsynaptic (PSD-95 and SNAP-23) regions of the synapses in the cortexes and hippocampi of the Aß1-42-injected mice, contributing to cognitive improvement in AD and improving the behavioral deficits displayed in the Morris water maze and Y-maze. Overall, our data suggest that NMP provides potent multifactorial effects, including the inhibition of amyloid plaques, oxidative stress, neuroinflammation, and cognitive deficits.

Revolutionizing Diabetes Diagnosis: Machine Learning Techniques Unleashed.

The intricate and multifaceted nature of diabetes disrupts the body's crucial glucose processing mechanism, which serves as a fundamental energy source for the cells. This research aims to predict the occurrence of diabetes in individuals by harnessing the power of machine learning algorithms, utilizing the PIMA diabetes dataset. The selected algorithms employed in this study encompass Decision Tree, K-Nearest Neighbor, Random Forest, Logistic Regression, and Support Vector Machine. To execute the experiments, two software tools, namely Waikato Environment for Knowledge Analysis (WEKA) version 3.8.1 and Python version 3.10, were utilized. To evaluate the performance of the algorithms, several metrics were employed, including true positive rate, false positive rate, precision, recall, F-measure, Matthew's correlation coefficient, receiver operating characteristic area, and precision-recall curves area. Furthermore, various errors such as Mean Absolute Error, Root Mean Squared Error, Relative Absolute Error, and Root Relative Squared Error were examined to assess the accuracy of the models. Upon conducting the experiments, it was observed that Logistic Regression outperformed the other techniques, exhibiting the highest precision of 81 percent using Python and 80.43 percent using WEKA. These findings shed light on the efficacy of machine learning in predicting diabetes and highlight the potential of Logistic Regression as a valuable tool in this domain.

Applicability of Titanium-Based Catalysts in the Photocatalytic Degradation of 2,3,7,8-Tetrachlorodibenzofuran.

Polychlorinated dibenzofurans (PCDFs) are persistent toxic compounds that are ubiquitous in the environment. Nanocomposites of titanium(IV) oxide-vanadium(III) oxide (Ti3V2O7) and titanium(IV) oxide-silicon dioxide (Ti2Si7O30) were prepared and spectroscopically analyzed as potential decontaminants for dioxin-like materials. The analysis confirmed a homogeneous morphology with nanoscale particle size. The Ti-Si sample was found to have a high surface area compared to the Ti-V composite. Vanadium(III) oxide (V2O5) and silicon dioxide (SiO2) were chosen as materials for the formation of heterogeneous compounds with titanium(IV) oxide (TiO2) because they possess a suitable band alignment with TiO2, thus forming effective photocatalysts. This study evaluated the photodegradation of 2,3,7,8-tetrachlorodibenzo-furan (TCDF) in the presence of Ti-Si and Ti-V oxide composites, which was tested using high- (254 nm) and midenergy (302 nm) UV irradiation sources. While Ti-Si showed success in the photodegradation of 2,3,7,8-TCDF dissolved in a (1:1) methanol-tetrahydrofuran (MeOH-THF) solution, the Ti-V composite proved to be a powerful material in adsorbing TCDF with a high capacity immediately upon mixing. Ti-Si oxide was found to decompose TCDF under the two irradiation sources with 98-99% degradation occurring after 70 min. The use of 254 nm as an irradiation source in the presence of Ti-Si was 4.3 times faster than the analogue reaction irradiated without a catalyst. Byproducts of the degradation were evaluated using gas chromatography-mass spectrometry (GC-MS), resulting in a lower chlorinated congener and less toxicity, as the main degradation product.

Alveolar Type 2 Epithelial Cell Organoids: Focus on Culture Methods.

Lung diseases rank third in terms of mortality and represent a significant economic burden globally. Scientists have been conducting research to better understand respiratory diseases and find treatments for them. An ideal in vitro model must mimic the in vivo organ structure, physiology, and pathology. Organoids are self-organizing, three-dimensional (3D) structures originating from adult stem cells, embryonic lung bud progenitors, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). These 3D organoid cultures may provide a platform for exploring tissue development, the regulatory mechanisms related to the repair of lung epithelia, pathophysiological and immunomodulatory responses to different respiratory conditions, and screening compounds for new drugs. To create 3D lung organoids in vitro, both co-culture and feeder-free methods have been used. However, there exists substantial heterogeneity in the organoid culture methods, including the sources of AT2 cells, media composition, and feeder cell origins. This article highlights the currently available methods for growing AT2 organoids and prospective improvements to improve the available culture techniques/conditions. Further, we discuss various applications, particularly those aimed at modeling human distal lung diseases and cell therapy.

Patterns of Common Dermatological Conditions among Children and Adolescents in Pakistan.

Background and Objectives: Dermatological disorders are highly prevalent among children in Pakistan. The present cross-sectional study aims to identify the spectrum of dermatological conditions among children and adolescents in Pakistan. Materials and Methods: A total of 582 patients (50.9% males; 49.1% females) were included in the study based on their age (5.7 ± 4.1 years), dermatological condition, and epidemiology. The youngest patient was aged ten days, whereas the eldest was seventeen. Age criteria were further stratified into three categories: infants and toddlers (≤5 years), children (≥5 to <12 years), and adolescents (≥12 to <18 years). Amongst them, the majority was from Punjab (81.6%), while the other regions included were Azad Jammu and Kashmir (14.4%), Islamabad (3.3%), and Khyber Pakhtunkhwa (0.7%). Results: Scabies was the highest reported skin condition with 281 (45.55%) patients, followed by 114 (19.6%) with eczema, 60 (10.3%) with dermatitis, 33 (5.7%) with tinea capitis, 17 (2.9%) with tinea corporis, 16 (2.7%) with impetigo, and 15 (2.6%) with folliculitis. Other conditions include urticaria, burns, infections, pediculosis, tinea inguinalis, tinea faciei, nappy rashes, alopecia, warts, tinea incognito, tinea cruris, and acne vulgaris. The chi-squared test showed a high prevalence of tinea corporis and acne among adolescents (12-17 years), whereas eczema, dermatitis, and impetigo were more prevalent among infants and toddlers. Conclusions: Pets or livestock and poor hygiene were found to be highly reported risk factors for many dermatological conditions like scabies and fungal infections. Dermatological conditions are common in younger individuals, but unfortunately, many children do not receive the desired medical assistance.

Development and characterization of letrozole-encapsulated polymeric beads for sustained release.

The study aimed to prepare and characterize biodegradable sustained-release beads of letrozole (LTZ) for treating cancerous disease. The ionotropic gelation method was used for the preparation and calcium chloride (CaCl2) was used as a gelating agent, while chitosan (CTS) and sodium alginate (NaAlg) as biodegradable polymeric matrices in the blend hydrogel beads. The beads were characterized for their size, surface morphology, drug entrapment efficiency, drug-polymer interaction and crystallinity using different analytic techniques, including optical microscopy, Scanning Electron Microscopy (SEM), UV-spectroscopy, Fourier-transform Infrared Spectroscopy (FTIR), Thermo gravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC) and X-ray Diffraction Analysis (XRD) respectively. In vitro swelling studies were also applied to observe the response of these polymeric networks against different pH (at 1.2, 6.8 and 7.4 pH). The results from TGA and DSC exhibited that the components in the formulation possess better thermal stability. The XRD of polymeric networks displays a minor crystalline and significant amorphous nature. The SEM micrographs revealed that polymeric networks have uneven surfaces and grooves. Better swelling and in vitro outcomes were achieved at a high pH (6.8,7.4), which endorsed the pH-responsive characteristics of the prepared beads. Hence, beads based on chitosan and sodium alginate were successfully synthesized and can be used for the controlled release of letrozole.

Unveiling Oxidative Stress-Induced Genotoxicity and Its Alleviation through Selenium and Vitamin E Therapy in Naturally Infected Cattle with Lumpy Skin Disease.

Lumpy skin disease (LSD) is a contagious infection of cattle caused by a virus of the Poxviridae family, genus Capripoxvirus. In Pakistan, recent outbreaks have resulted in significant nationwide mortality and economic losses. A 20-day prospective cohort study was performed on sixty infected cattle with the aim to evaluate LSD-induced oxidative stress's genotoxic role and to determine the ameliorative effect of antioxidant therapy using principal component analysis (PCA) and a multivariable ordinal logistic regression model. LSDV was identified from scab samples and nodular lesions using RPO30-specific gene primers. The infected cattle were divided into control and treated groups. The animals were observed initially and finally on day 20 to evaluate the homeostatic, oxidative, and genotoxic changes. The animals in the treated group were administered a combination of selenium (Se) and vitamin E at the standard dose rate for five consecutive days. A substantial (p < 0.05) improvement in the hematological indices was observed in the treated group. The treated group also showed a significant (p < 0.05) reduction in levels of serum nitric oxide (NO) and malondialdehyde (MDA) post-therapy. The PCA at the final sampling data of the treated group showed that Principal Component (PC1 eigenvalue 1.429) was influenced by superoxide dismutase (SOD; 0.3632), catalase (CAT; 0.2906), and glutathione (GSH; 0.0816) and PC2 (eigenvalue 1.200) was influenced by CAT (0.4362), MDA (0.2056), and NO (0.0693). A significant correlation between serum NO (76%) and MDA levels (80%) was observed with genetic damage index (GDI) scores. The ordinal logistic regression model regarding the use of antioxidant therapy revealed 73.95-times (95%CI; 17.36-314.96) improvement in the GDI in treated animals. The multivariable ordinal logistic regression showed that each unit increase in NO and MDA resulted in a 13% increase in genotoxicity in infected individuals. In conclusion, our study revealed that LSD-induced oxidative stress and lipid peroxidation product causes genotoxicity in affected animals. Furthermore, the combined Se and vitamin E therapy significantly alleviated oxidative stress and genotoxicity in LSD-affected cattle.

Dual activity of indolin-2-ones containing an arylidene motif: DNA and BSA interaction.

Applying a multistep approach, novel indolin-2-ones (IND) that possess an arylidene motif have been synthesized. Eight compounds were chosen for different biological tests (antimicrobial and cytotoxicity). IND containing 2-thienyl (4h) fragment have been found to exhibit good antimicrobial activity against B. cereus. Molecules that have 3-aminophenyl (4d) or 2-pyridyl (4g) groups have shown the best antifungal activities against all tested fungi. These compounds have also been noticed as promising pharmaceuticals against MCF-7 cancer cell lines. Experimental outcomes from the investigation of the interaction of 4d with DNA implied its moderate binding to DNA (KSV = 1.35 × 104 and 3.05 × 104 M-1 for EB and Hoechst binder, respectively). However, considerably stronger binding of 4d to BSA has been evidenced (Ka = 6.1 × 106 M-1). In summary, IND that contains m-aminobenzylidene fragment (4d) exhibits a good dual biological activity making it a promising candidate for further investigation in the drug discovery sector.

Wnt signaling pathway inhibitor promotes mesenchymal stem cells differentiation into cardiac progenitor cells in vitro and improves cardiomyopathy in vivo.

BACKGROUND: Cardiovascular diseases particularly myocardial infarction (MI) are the leading cause of mortality and morbidity around the globe. As cardiac tissue possesses very limited regeneration potential, therefore use of a potent small molecule, inhibitor Wnt production-4 (IWP-4) for stem cell differentiation into cardiomyocytes could be a promising approach for cardiac regeneration. Wnt pathway inhibitors may help stem cells in their fate determination towards cardiomyogenic lineage and provide better homing and survival of cells in vivo. Mesenchymal stem cells (MSCs) derived from the human umbilical cord have the potential to regenerate cardiac tissue, as they are easy to isolate and possess multilineage differentiation capability. IWP-4 may promote the differentiation of MSCs into the cardiac lineage. AIM: To evaluate the cardiac differentiation ability of IWP-4 and its subsequent in vivo effects. METHODS: Umbilical cord tissue of human origin was utilized to isolate the MSCs which were characterized by their morphology, immunophenotyping of surface markers specific to MSCs, as well as by tri-lineage differentiation capability. Cytotoxicity analysis was performed to identify the optimal concentration of IWP-4. MSCs were treated with 5 µM IWP-4 at two different time intervals. Differentiation of MSCs into cardiomyocytes was evaluated at DNA and protein levels. The MI rat model was developed. IWP-4 treated as well as untreated MSCs were implanted in the MI model, then the cardiac function was analyzed via echocardiography. MSCs were labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) dye for tracking, while the regeneration of infarcted myocardium was examined by histology and immunohistochemistry. RESULTS: MSCs were isolated and characterized. Cytotoxicity analysis showed that IWP-4 was non-cytotoxic at 5 µM concentration. Cardiac specific gene and protein expression analyses exhibited more remarkable results in fourteen days treated group that was eventually selected for in vivo transplantation. Cardiac function was restored in the IWP-4 treated group in comparison to the MI group. Immunohistochemical analysis confirmed the homing of pre-differentiated MSCs that were labeled with DiI cell labeling dye. Histological analysis confirmed the significant reduction in fibrotic area, and improved left ventricular wall thickness in IWP-4 treated MSC group. CONCLUSION: Treatment of MSCs with IWP-4 inhibits Wnt pathway and promotes cardiac differentiation. These pre-conditioned MSCs transplanted in vivo improved cardiac function by cell homing, survival, and differentiation at the infarcted region, increased left ventricular wall thickness, and reduced infarct size.

RP-HPLC method to assay ethinylestradiol and drospirenone with 3D chromatograph model in fixed dose in rat plasma for pharmacokinetic study analysis.

For the simultaneous measurement of Ethinylestradiol (EE) and Drospirenone (DP) in fixed-dose combination hormones tablets, a reverse-phase high-performance liquid chromatographic (RP-HPLC) method was developed. A specific, precise and accurate RP-HPLC method was developed and validated to analyse the drugs in rat plasma. The fluorescence detection for EE was made at λ= 200-310 nm and Ultraviolet-visible (UV/Vis) detection for DP was made at 270 nm. The typical EE and DP retention times were 4.19 and 5.30 minutes, respectively. The limit of detection (LOD) and limit of detection (LOQ) for EE were 0.121 and 0.282µg/mL and LOD and LOQ for DP were 2.23 and 7.697µg/mL respectively. The regression coefficient (r2) of EE and DP were 0.9937 and 0.9913 respectively. Precision's relative standard deviation (RSD) was less than 5%. The analyte recoveries of both drugs stayed within 95% of each other. All other validation parameters adhered to ICH standards. Throughout the analytical process, the analyte was stable. The advantages of the method developed include stability under different conditions and a low limit of quantification that was in micrograms. Its applicability was confirmed by the analysis of EE and DP levels in plasma samples in a designed pharmacokinetic study in rats after oral administration.