Therapeutic potential of popular fermented dairy products and its benefits on human health.

In the current arena of time, the transformation of society has improved the standard of living in terms of lifestyle and their nutritional demands and requirements. The microorganisms under controlled conditions and the enzymatic transformation of dietary components are the processes that resulted in fermented foods and beverages. Fermented dairy products with high nutritional value are "the pearls of the dairy industry." During fermentation, fermented dairy products produce bioactive compounds and metabolites derived from bacteria. Research indicates the beneficial effects of probiotics found in dairy products on human health is making lightning-fast headway these days. The utilization of lactic acid bacteria as probiotics for the prevention or treatment of disease has been a driving force behind the discovery of novel potential probiotics found in naturally fermented milk. Probiotics such as lactic acid bacteria and bifidobacteria found in fermented dairy products have a variety of health benefits, including innate immune enhancement, diarrhea treatment, inflammatory bowel disease, diabetes, Tuberculosis, and obesity, relieving irritable bowel disease symptoms, preventing cancer, improving lactose tolerance, lowering cholesterol, enhancing antioxidant activity, and antimicrobial activity against pathogens. This review aims to evaluate the therapeutic efficacy and nutritional and microbiological properties of popular fermented dairy products and their health benefits.

In-situ Gels for Brain Delivery: Breaching the Barriers.

The blood-brain barrier (BBB) regulates blood and chemical exchange in the central nervous system. It is made up of brain parenchyma capillary endothelial cells. It separates the interstitial cerebrospinal fluid from the circulation and limits brain drug entry. Peptides, antibodies, and even tiny hydrophilic biomolecules cannot flow across the BBB due to their semi-permeability. It protects the brain from poisons, chemicals, and pathogens, and blood cells penetrate brain tissue. BBB-facilitated carrier molecules allow selective permeability of nutrients such as D-glucose, L-lactic acid, L-phenylalanine, L-arginine, and hormones, especially steroid hormones. Brain barriers prevent drug molecules from entering, making medication delivery difficult. Drugs can reach specific brain regions through the nasal cavity, making it a preferred route. The in-situ gels are mucoadhesive, which extends their stay in the nasal cavity, allows them to penetrate deep and makes them a dependable way of transporting numerous medications, including peptides and proteins, straight into the central nervous system. This approach holds great potential for neurological therapy as they deliver drugs directly to the central nervous system, with less interference and better drug release control. The brain affects daily life by processing sensory stimuli, controlling movement and behaviour, and sustaining mental, emotional, and cognitive functioning. Unlike systemic routes, the nasal mucosa is extensively vascularized and directly contacts olfactory sensory neurons. Compared to the systemic circulation, this improves brain bioavailability of medications. Drugs can be delivered to the brain using in-situ gel formulations safely and efficiently, with a greater therapeutic impact than with traditional techniques.

Vaccines in Breast Cancer: Challenges and Breakthroughs.

Breast cancer is a problem for women's health globally. Early detection techniques come in a variety of forms ranging from local to systemic and from non-invasive to invasive. The treatment of cancer has always been challenging despite the availability of a wide range of therapeutics. This is either due to the variable behaviour and heterogeneity of the proliferating cells and/or the individual's response towards the treatment applied. However, advancements in cancer biology and scientific technology have changed the course of the cancer treatment approach. This current review briefly encompasses the diagnostics, the latest and most recent breakthrough strategies and challenges, and the limitations in fighting breast cancer, emphasising the development of breast cancer vaccines. It also includes the filed/granted patents referring to the same aspects.

Synthesis and Mechanistic Insights of the Formation of 3-Hydroxyquinolin-2-ones including Viridicatin from 2-Chloro-N,3-diaryloxirane-2-carboxamides under Acid-Catalyzed Rearrangements.

N-Benzyl-2-chloro-N,3-diaryloxirane-2-carboxamides, easily obtained from aromatic aldehydes and anilides of dichloroacetic acid under Darzens condensation conditions, proved to be excellent starting compounds for the synthesis of 3-hydroxyindolin-2-ones, cyclohepto[b]pyrrole-2,3-diones, and 1-azaspiro[4.5]deca-3,6,9-triene-2-ones via the C(sp2)-C(sp2) bond formation in the first case and C(sp2)-C(sp3) bond formation in the second and third cases. Under optimized reaction conditions, 3-hydroxyindolin-2-ones are obtained in a one-pot process, which involves the treatment of N-benzyl-2-chloro-N,3-diaryloxirane-2-carboxamides with CF3CO2H or AcOH/H2SO4. In the case of intramolecular cyclization, the detailed reaction channels depend strongly on the substituents present in the anilide component and in the aromatic ring of the aldehyde component of N-benzyl-2-chloro-N,3-diaryloxirane-2-carboxamides, as well as the temperature and duration of the reaction. A combined experimental and DFT mechanistic study of the formation of 1-benzyl-3-hydroxy-4-arylquinolin-2(1H)-ones showed that there are three competing reaction channels: (a) ring-closure via the ipso site, (b) ring-closure via the 1,2-Cl shift, and (c) ring-closure via the ortho site. Such mechanistic insights enabled an effective one-pot gram-scale synthesis of viridicatin from benzaldehyde and 2,2-dichloro-N-(4-methoxybenzyl)-N-phenylacetamide.

Robust proportional overlapping analysis for feature selection in binary classification within functional genomic experiments.

In this paper, a novel feature selection method called Robust Proportional Overlapping Score (RPOS), for microarray gene expression datasets has been proposed, by utilizing the robust measure of dispersion, i.e., Median Absolute Deviation (MAD). This method robustly identifies the most discriminative genes by considering the overlapping scores of the gene expression values for binary class problems. Genes with a high degree of overlap between classes are discarded and the ones that discriminate between the classes are selected. The results of the proposed method are compared with five state-of-the-art gene selection methods based on classification error, Brier score, and sensitivity, by considering eleven gene expression datasets. Classification of observations for different sets of selected genes by the proposed method is carried out by three different classifiers, i.e., random forest, k-nearest neighbors (k-NN), and support vector machine (SVM). Box-plots and stability scores of the results are also shown in this paper. The results reveal that in most of the cases the proposed method outperforms the other methods.

Ranolazine-functionalized CuO NPs: efficient homogeneous and heterogeneous catalysts for reduction of 4-nitrophenol.

In the present study copper oxide nanoparticles (CuO NPs) were synthesized using a hydrothermal method with ranolazine as a shape-directing agent. Ranolazine-functionalized CuO NPs were characterized by various analytical techniques such as scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD). The SEM pattern confirmed the morphology of ranolazine-functionalized CuO NPs with well-defined rice-like structures. FTIR spectroscopy confirmed the interaction between CuO NPs and ranolazine. The XRD analysis indicated that the structure of ranolazine-functionalized CuO NPs was monoclinic crystalline and the size ranged between 9 and 18 nm with an average particle size of 12 nm. The smaller size range of CuO NPs gave a large surface area that enhanced the efficiency of these catalysts employed for the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) in the H 2 O system. In homogeneous catalysis, results showed that 50 µL of CuO NPs was required in the presence of NaBH4 for 99% reduction of 4-NP in 240 s. On the other hand, for heterogeneous catalysis, 0.5 mg of CuO NPs was used in the presence of NaBH4 for 99% catalytic reduction of 4-NP to 4-AP in 320 s. The rate of reaction for homogeneous catalysis and heterogeneous catalysis was determined from the plots of In(Ct /C0) of 4-NP versus time (s), which showed good linearity with values of 1.3 × 10 -2 and 8.8 × 10 -3 s -1 . respectively. The high-quality catalytic efficiency, good reusability, nontoxic nature, and low cost are favorable properties of the synthesized CuO NPs for use as efficient catalysts for reduction of 4-AP to 4-NP in both homogeneous and heterogeneous media.

Regulatory genes identification within functional genomics experiments for tissue classification into binary classes via machine learning techniques.

OBJECTIVE: The aim of this study is to filter out the most informative genes that mainly regulate the target tissue class, increase classification accuracy, reduce the curse of dimensionality, and discard redundant and irrelevant genes. METHOD: This paper presented the idea of gene selection using bagging sub-forest (BSF). The proposed method provided genes importance grounded on the idea specified in the standard random forest algorithm. The new method is compared with three state-of-the art methods, i.e., Wilcoxon, masked painter and proportional overlapped score (POS). These methods were applied on 5 data sets, i.e. Colon, Lymph node breast cancer, Leukaemia, Serrated colorectal carcinomas, and Breast Cancer. Comparison was done by selecting top 20 genes by applying the gene selection methods and applying random forest (RF) and support vector machine (SVM) classifiers to assess their predictive performance on the datasets with selected genes. Classification accuracy, Brier score, and sensitivity have been used as performance measures. RESULTS: The proposed method gave better results than the other methods using both random forest and SVM classifiers on all the datasets among all the feature selection methods. CONCLUSIONS: The proposed method showed improved performance in terms of classification accuracy, Brier score and sensitivity, and hence, could be used as a novel method for gene selection to classify tissue samples into their correct classes.

Ranolazine-Functionalized Copper Nanoparticles as a Colorimetric Sensor for Trace Level Detection of As3.

This study involves environmentally friendly synthesis of copper nanoparticles in aqueous medium without inert gas protection, using ranolazine as a capping material. UV-Visible (UV-Vis) spectrometry showed that ranolazine-derived copper nanoparticles (Rano-Cu NPs) demonstrate a localized surface plasmon resonance (LSPR) band at 573 nm with brick-red color under optimized parameters, including pH, reaction time, and concentrations of copper salt, hydrazine hydrate, and ranolazine. The coating of ranolazine on the surface of Cu NPs was studied via Fourier transform infrared (FTIR) spectroscopy. Scanning electron microscopy (SEM) revealed that Rano-Cu NPs consist of spherical particles. X-ray diffraction (XRD) verified that Rano-Cu NPs are crystalline in nature. Atomic force microscopy (AFM) showed that the average size of Rano-Cu NPs was 40 ± 2 nm in the range of 22⁻95 nm. Rano-Cu NPs proved to be highly sensitive as a selective colorimetric sensor for As3+ via color change from brick red to dark green, in the linear range of 3.0 × 10-7 to 8.3 × 10-6 M, with an R² value of 0.9979. The developed sensor is simple, cost effective, highly sensitive, and extremely selective for As3+ detection, showing a low detection limit (LDL) of 1.6 × 10-8 M. The developed sensor was effectively tested for detection of As3+ in some water samples.

Synthesis of 3-Hydroxy-4-arylquinolin-2-ones Including Viridicatol via a Darzens Condensation/Friedel-Crafts Alkylation Strategy.

The new efficient synthesis of biologically important 3-hydroxy-4-arylquinolin-2-ones through the Darzens condensation (epoxidation) of dichloroacetanilides with aromatic aldehydes followed by one-pot dechlorative epoxide-arene cyclization is described. This methodology has been utilized for the synthesis of naturally occurring viridicatol, a fungal metabolite isolated from the penicillium species.

Prevalence of Giardia intestinalis and Hymenolepis nana in Afghan refugee population of Mianwali district, Pakistan.

BACKGROUND: Present study aimed to investigate prevalence of Giardia intestinalis and Hymenolepis nana in Afghan refugees visiting Central Health Unit (CHU), Kot Chandana (Mianwali, Northern Punjab) during two years period (February 2007 to December 2009). METHODS: A total of 687 stool samples were collected from different age groups of both genders. Samples were processed under sterile conditions after gross examination. Microscopic examination was done on same day along with eggs (H. nana), cyst and trophozoites (G. intestinalis) detection after staining. RESULTS: The prevalence of G. intestinalis was significantly higher (x2=59.54, p<0.001) than that of H. nana. Females were found more likely to be infected as compared to males (OR: 1.40, 95% CI=1.03-1.92). Prevalence of both parasites decreased with age and highest prevalence was observed in young individuals belonging to 1-15 years of age group (41.8% and 48.7% respectively for H. nana and G. intestinalis, p<0.001). Abdominal distress (OR: 1.13, 95%CI=0.83-1.53), vomiting (OR: 1.13, 95%CI=1.13-1.81) and rectal prolapse (OR: 4.26, 95%CI=1.38-13.16) were the gastro-intestinal clinical symptoms observed in G. intestinalis. Whereas, bloody diarrhea (OR: 1.56, 95%CI=1.00-2.43) and rectal prolapse (OR: 5.79, 95%CI=1.87-17.91) were associated with H. nana infections. CONCLUSIONS: Intestinal parasitic infections are common among Afghan refugees and serious preventive measures should be implemented to promote the safety and healthy lifestyle of these people.

4-Thiazolidinones: the advances continue .

The diversity in the biological response of 4-thiazolidinones has attracted the attention of many researchers to explore this framework for its potential. It is, therefore, of prime importance that the study of this topic and the development of new synthetic strategies should be based on the most recent knowledge, emerging from the latest research. This review is an endeavor to highlight the progress in the chemistry and biological activity of the 4-thiazolidinones, predominantly after 2006. The last section of the review encompasses the various patents granted on 4-thiazolidinone analogs/derivatives with World Intellectual Proprietary Organization (WIPO) and United State Patent Trademark Office (USPTO), particularly in the duration of the year 2000 to the year 2012.

Patterns of argyrophilic nucleolar organiser regions in pleural and peritoneal effusions.

OBJECTIVE: To evaluate AgNOR size and dispersion as alternate methods to AgNOR counts in order to differentiate malignant from non-malignant effusions. DESIGN: Comparative study. PLACE AND DURATION OF STUDY: Department of Pathology, Postgraduate Medical Institute, Lahore, from January 2003 to June 2004. MATERIALS AND METHODS: A total of 240 samples of pleural and peritoneal effusions were centrifuged, deposits smeared on slides and stained with H and E and AgNOR stain. The diagnosis of malignancy or otherwise was made on H and E staining. AgNOR counts, variation in size and dispersion of AgNOR dots in smears were graded and compared in malignant and non-malignant effusions. RESULTS: Mean AgNOR counts of 11.47+/-3.60 and 11.04+/-3.89 in malignant pleural and peritoneal effusions, respectively, were significantly (p<0.0001) greater as compared with counts of 3.36+/-0.69 and 3.35+/-0.66 in non-malignant effusions. AgNOR size and dispersion were of higher grade in significantly greater proportion of malignant as compared with non-malignant effusions (p<0.0001). CONCLUSION: Typing of AgNOR size and dispersion was found to be an easy and reproducible alternative to traditional AgNOR counts for differentiating malignant from non-malignant effusions. These parameters should be correlated with already established but expensive techniques of AgNOR area and size imaging by electron microscopy and flow cytometry, as an economical alternative.