Study on anti-diarrheal activities of Abelmoscous esculentus seeds

The main objective of this study is to analyze anti-diarrheal activities of Abelmoscous esculentus. Phytochemical screening shows that Abelmoscous esculentus contain alkaloid, carbohydrate, saponines, diterpene, phytosterol, proteins and gums. Ethanolic extract of Abelmoscous esculentus as well as n-hexane soluble fraction and chloroform soluble fraction show 81.82% anti-diarrheal activities that is much higher than standard Loperamide (63.64%). Â

LDDNet: a deep learning framework for the diagnosis of infectious lung diseases.

This paper proposes a new deep learning (DL) framework for the analysis of lung diseases, including COVID-19 and pneumonia, from chest CT scans and X-ray (CXR) images. This framework is termed optimized DenseNet201 for lung diseases (LDDNet). The proposed LDDNet was developed using additional layers of 2D global average pooling, dense and dropout layers, and batch normalization to the base DenseNet201 model. There are 1024 Relu-activated dense layers and 256 dense layers using the sigmoid activation method. The hyper-parameters of the model, including the learning rate, batch size, epochs, and dropout rate, were tuned for the model. Next, three datasets of lung diseases were formed from separate open-access sources. One was a CT scan dataset containing 1043 images. Two X-ray datasets comprising images of COVID-19-affected lungs, pneumonia-affected lungs, and healthy lungs exist, with one being an imbalanced dataset with 5935 images and the other being a balanced dataset with 5002 images. The performance of each model was analyzed using the Adam, Nadam, and SGD optimizers. The best results have been obtained for both the CT scan and CXR datasets using the Nadam optimizer. For the CT scan images, LDDNet showed a COVID-19-positive classification accuracy of 99.36%, a 100% precision recall of 98%, and an F1 score of 99%. For the X-ray dataset of 5935 images, LDDNet provides a 99.55% accuracy, 73% recall, 100% precision, and 85% F1 score using the Nadam optimizer in detecting COVID-19-affected patients. For the balanced X-ray dataset, LDDNet provides a 97.07% classification accuracy. For a given set of parameters, the performance results of LDDNet are better than the existing algorithms of ResNet152V2 and XceptionNet

RFLPs of ITS, ITS1 and hsp70 amplicons and sequencing of ITS1 of recent clinical isolates of Kala-azar from India and Bangladesh confirms the association of L. tropica with the disease

Visceral Leishmaniasis or Kala-azar (KA) is a serious health concern in India. In the present study, Restriction Fragment Length Polymorphism (RFLP) of three genetic markers viz., Internal Transcribed Spacer (ITS), ITS1 and heat shock protein 70 (hsp70) have been employed for typing the clinical isolates [n = 15] of KA and post Kala-azar Dermal Leishmaniosis (PKDL) collected from India and Bangladesh in the period of 2006–2010. Experimentally, ITS, ITS1 and hsp70 regions of genomes of all the clinical isolates were separately amplified by PCR and then digested with restriction enzymes: ITS with Alu1, EcoR1 and Msp1, ITS1 with Hae III and Rsa1 and hsp70 with Hae III. The resultant fragments were analyzed by agarose gel electrophoresis and the RFLP profiles of the clinical isolates were compared with that of the WHO reference strains for Leishmania donovani (DD8) and Leishmania tropica (K27), respectively. Also, the ITS1 regions of all the clinical isolates along with the two WHO reference strains were sequenced and a phylogram was constructed to ascertain the extent of similarity or dissimilarity. Interestingly, the RFLP profiles of one of the isolates showed a significant homology with K27 and the phylogram revealed its closeness with the same putting credence to our earlier typing of isolates by RAPD method. This observation also supported an earlier report claiming that both the species are responsible for KA in India and thus, emphasizes urgent need for thorough systematic characterization of the clinical isolates of Indian KA as appropriate treatment regime relies primarily on proper diagnosis

Synthesis and Assessment of Fertility-Regulating Potential of 2-(2″-chloroacetamidobenzyl)-3-(3′-indolyl) Quinoline in Adult Rats as a Male Contraceptive Agent.

Background: The purpose of this study was to investigate the fertility-regulating potential of the compound 2-(2″-chloroacetamidobenzyl)- 3-(3′-indolyl) quinoline in male rats. Study Design: Rats of proven fertility were treated with the compound by oral gavage for 1 to 8 consecutive weeks. Functional fertility, testicular, epididymal and seminal vesicular weight, epididymal sperm count and spermatogenesis were quantitated. Reproductive hormones and some biochemical parameters were measured. Results: Functional fertility was reduced significantly as revealed by a fall in fertility and pregnancy rate. The weight of the reproductive organs was reduced significantly. A reduction of sperm count and number of different types of testicular cells was observed. The treatment with the compound resulted in decline of testosterone and an increase of FSH hormone levels. The compound effectively reduced testicular protein, glycogen and epididymal glyceryl phosphorylcholine. Increase in testicular alkaline phosphatase and cholesterol was also observed. Fertility and other effects were regained gradually after cessation of treatment. Conclusion: The results revealed from the study indicate that the compound has reversible antifertility activity and can be explored as male contraceptive agent

Characterization of the recent clinical isolates of Indian Kala-azar patients by RAPD-PCR method

Leishmaniasis is one of the most important vector borne diseases caused by kinetoplastid protozoa Leishmania sp. Among all forms of Leishmaniasis, Visceral leishmaniasis (VL) or Kala-azar is the severest form of the illness. VL is characterized by fever, hepatosplenomegaly, anaemia, edema, weight loss and invariably fatal if left untreated. Characterization of Leishmania sp. is extremely necessary to understand the epidemiology, taxonomy and population genetics of the parasites which ultimately helps in designing appropriate drug regimen to combat the disease. In this study, we aimed to type the clinical isolates of Leishmania species collected in the period 2006–2010 from patients (n = 9) diagnosed with Kala-azar and post Kala-azar dermal leishmaniasis (PKDL) by RAPD-PCR method using eight selected primers. Genome of the clinical isolates were amplified and electrophoresed in agarose gel. These were compared with the RAPD PCR profiles of WHO reference strains for L. donovani (DD8) and L. tropica (K27) respectively. We calculated the Jaccard’s Similarity Coefficient and found one (study code T5) out of nine isolates as L. tropica while the rest were L. donovani. This pilot study supports the earlier single report claiming that both the species are responsible for Kala-azar in India and it also emphasizes the need for more systematic typing of clinical isolates of Indian Kala-azar

Ligand-Induced Tuning of the Oxidase Activity of μ‑Hydroxidodimanganese(III) Complexes Using 3,5-Di-<i>tert</i>-butylcatechol as the Substrate: Isolation and Characterization of Products Involving an Oxidized Dioxolene Moiety

Oxidase activities of a μ-hydroxidodimanganese­(III) system involving a series of tetradentate capping ligands H₂L^R₁,R₂ with a pair of phenolate arms have been investigated in the presence of 3,5-di-<i>tert</i>-butylcatechol (H₂DBC) as a coligand cum-reductant. The reaction follows two distinctly different paths, decided by the substituent combinations (R₁ and R₂) present in the capping ligand. With the ligands H₂L^{<i>t</i>‑Bu,<i>t</i>‑Bu} and H₂L^{<i>t</i>‑Bu,OMe}, the products obtained are semiquinonato compounds [Mn^III(L^{<i>t</i>‑Bu,<i>t</i>‑Bu})­(DBSQ)]·2CH₃OH (<b>1</b>) and [Mn^III(L^{<i>t</i>‑Bu,OMe})­(DBSQ)]·CH₃OH (<b>2</b>), respectively. In the process, molecular oxygen is reduced by two electrons to generate H₂O₂ in the solution, as confirmed by iodometric detection. With the rest of the ligands, viz., H₂L^Me,Me, H₂L^{<i>t</i>‑Bu,Me}, H₂L^{Me,<i>t</i>‑Bu}, and H₂L^Cl,Cl, the products initially obtained are believed to be highly reactive quinonato compounds [Mn^III(L^R₁,R₂)­(DBQ)]⁺, which undergo a domino reaction with the solvent methanol to generate products of composition [Mn^III(L^R₁,R₂)­(BMOD)] (<b>3</b>–<b>6</b>) involving a nonplanar dioxolene moiety, viz., 3,5-di-<i>tert</i>-butyl-3-methoxy-6-oxocyclohexa-1,4-dienolate (BMOD^–). This novel dioxolene derivative is formed by a Michael-type nucleophilic 1,4-addition reaction of the methoxy group to the coordinated quinone in [Mn^III(L^R₁,R₂)­(DBQ)]⁺. During this reaction, molecular oxygen is reduced by four electrons to generate water. The products have been characterized by single-crystal X-ray diffraction analysis as well as by spectroscopic methods and magnetic measurements. Density functional theory calculations have been made to address the observed influence of the secondary coordination sphere in tuning the two-electron versus four-electron reduction of dioxygen. The semiquinone form of the dioxolene moiety is stabilized in compounds <b>1</b> and <b>2</b> because of extended electron delocalization via participation of the appropriate metal orbital(s)

A patch of positively charged residues regulates the efficacy of clinical DR5 antibodies in solid tumors.

Receptor clustering is the first and critical step to activate apoptosis by death receptor-5 (DR5). The recent discovery of the autoinhibitory DR5 ectodomain has challenged the long-standing view of its mechanistic activation by the natural ligand Apo2L. Because the autoinhibitory residues have remained unknown, here we characterize a crucial patch of positively charged residues (PPCR) in the highly variable domain of DR5. The PPCR electrostatically separates DR5 receptors to autoinhibit their clustering in the absence of ligand and antibody binding. Mutational substitution and antibody-mediated PPCR interference resulted in increased apoptotic cytotoxic function. A dually specific antibody that enables sustained tampering with PPCR function exceptionally enhanced DR5 clustering and apoptotic activation and distinctively improved the survival of animals bearing aggressive metastatic and recurrent tumors, whereas clinically tested DR5 antibodies without PPCR blockade function were largely ineffective. Our study provides mechanistic insights into DR5 activation and a therapeutic analytical design for potential clinical success

Nonoxido Vanadium(IV) Compounds Involving Dithiocarbazate-Based Tridentate ONS Ligands: Synthesis, Electronic and Molecular Structure, Spectroscopic and Redox Properties

A new series of nonoxido vanadium­(IV) compounds [VL₂] (L = L¹–L³) (<b>1</b>–<b>3</b>) have been synthesized using dithiocarbazate-based tridentate Schiff-base ligands H₂L¹–H₂L³, containing an appended phenol ring with a <i>tert</i>-butyl substitution at the 2-position. The compounds are characterized by X-ray diffraction analysis (<b>1</b>, <b>3</b>), IR, UV-vis, EPR spectroscopy, and electrochemical methods. These are nonoxido V^IV complexes that reveal a rare distorted trigonal prismatic arrangement around the “bare” vanadium centers. Concerning the ligand isomerism, the structure of <b>1</b> and <b>3</b> can be described as intermediate between <i>mer</i> and <i>sym-fac</i> isomers. DFT methods were used to predict the geometry, <b>g</b> and ⁵¹V <b>A</b> tensors, electronic structure, and electronic absorption spectrum of compounds <b>1</b>–<b>3</b>. Hyperfine coupling constants measured in the EPR spectra can be reproduced satisfactorily at the level of theory PBE0/VTZ, whereas the wavelength and intensity of the absorptions in the UV-vis spectra at the level CAM-B3LYP/gen, where “gen” is a general basis set obtained using 6-31+g­(d) for S and 6-31g for all the other elements. The results suggest that the electronic structure of <b>1</b>–<b>3</b> can be described in terms of a mixing among V-<i>d</i>_<i>xy</i>, V-<i>d</i>_<i>xz</i>, and V-<i>d</i>_<i>yz</i> orbitals in the singly occupied molecular orbital (SOMO), which causes a significant lowering of the absolute value of the ⁵¹V hyperfine coupling constant along the <i>x</i>-axis. The cyclic voltammograms of these compounds in dichloroethane solution display three one-electron processes, two in the cathodic and one in the anodic potential range. Process A (<i>E</i>_1/2 = +1.06 V) is due to the quasi-reversible V­(IV/V) oxidation while process B at <i>E</i>_1/2 = −0.085 V is due to the quasi-reversible V­(IV/III) reduction, and the third one (process C) at a more negative potential <i>E</i>_1/2 = −1.66 V is due to a ligand centered reduction, all potentials being measured vs Ag/AgCl reference