Exploring binding mode assessment of novel kaempferol, resveratrol, and quercetin derivatives with PPAR-α as potent drug candidates against cancer.

Peroxisome proliferator-activated receptors (PPAR)-α, a ligand-activated transcription factor stands out to be a valuable protein target against cancer. Given that ligand binding is the crucial process for the activation of PPAR-α, fibrate class of synthetic compounds serves as potent agonist for the receptor. However, their serious side effects limit the long-term application in cancer. This emphasizes the dire need to identify new candidates that would exert desired activation by abrogating the adverse effects caused by synthetic agonists. Natural dietary products serve as an important source of drug discovery. Hence, the present study encompasses the investigation of the role of natural plant phenolic compounds: kaempferol, resveratrol, and quercetin and their 8708 derivatives by the means of computational pipeline comprising molecular docking and molecular dynamic (MD) simulation techniques. Docking calculations shortlisted potential candidates, namely 6-cinnamylchrysin (6-CC), resveratrol potassium-4-sulfate (RPS) and 6-[2-(3,4-Dihydroxyphenyl)-5-hydroxy-4-oxochromen-7-yl]oxyhexyl nitrate (DHOON), and derivatives of kaempferol, resveratrol, and quercetin, respectively. 6-CC, RPS, and DHOON manifested better affinities of - 32.83 kcal/mol (Ala333, Lys358, His440), - 27.22 kcal/mol (Tyr314, Met355), and - 30.18 kcal/mol (Ser280, Tyr314, Ala333), respectively, and were found to act as good stimulants for PPAR-α. Among these three compounds, 6-CC caused relatively least deviations and fluctuations analyzed through MD simulation which judiciously held responsible to attain most favorable interaction with PPAR-α. Followed by the binding free energy (ΔG) calculations using MM-GBSA confirmed the key role of 6-CC toward PPAR-α. The compound 6-CC also achieved high drug-likeness and pharmacokinetic properties. Thus, these findings stipulate new drug leads for PPAR-α receptor which abets a way to develop new anti-cancer drugs.

Lagerstroemia speciosa (L.) Pers., ethanolic leaves extract attenuates dapsone-induced liver inflammation in rats.

Drug-induced liver injury is a common cause of acute liver failure. Dapsone is increasingly used in combination with rifampicin for the treatment of leprosy and also for several dermatological disorders. Clinically, abnormal liver function and focal bile duct destruction were reported after dapsone therapy. Lagerstroemia speciosa Pers., commonly known as Banaba has been traditionally used to treat various ailments including diabetes and obesity due to its antioxidant and anti-inflammatory efficacies. This study investigated the hepatoprotective effect of ethanolic banaba leaves extract (EBLE) against dapsone-induced hepatotoxicity in rats. Dapsone (30 mg/kg, i.p.) was administered twice daily for 30 days. In separate groups, rats were post-treated orally with EBLE (250 and 500 mg/kg) and silymarin (100 mg/kg) once daily for 30 days after dapsone administration. The marker enzymes of hepatotoxicity, oxidative stress markers, inflammatory markers and histopathology of liver were done. HPTLC analysis confirmed the presence of 12.87 µg of corosolic acid per mg of EBLE. Dapsone administration-induced significant (p < 0.001) elevation of marker enzymes of hepatotoxicity in serum. This treatment also increased lipid peroxidation (p < 0.001) and pro-inflammatory markers (tumor necrosis factor-alpha, transforming growth factor-beta, and nuclear factor kappa-B) expressions (p < 0.001) and decreased antioxidants (p < 0.001) such superoxide dismutase, catalase and glutathione in the liver tissue. All these abnormalities were significantly (p < 0.001) mitigated after EBLE (500 mg/kg) and silymarin post-treatments. The results of this study suggest that silymarin and EBLE can be used for dapsone-induced hepatotoxicity.

Ethanolic Extract of Lagerstroemia Speciosa (L.) Pers., Induces Apoptosis and Cell Cycle Arrest in HepG2 Cells.

Lagerstroemia speciosa (L.) Pers., (Lythraceae) also called Banaba is a native plant of southeast Asia and is widely used in traditional medicinal system. Herbal tea from banaba leaves are used to reduce weight and diabetes. We investigated the cytotoxic potentials of ethanolic banaba leaves extract (EBLE) against human hepatocellular carcinoma (HepG2) cell line. Lagerstroemia speciosa leaves were extracted and obtained from M/s. Quimico Herbal Extract Manufacturer, Bengaluru, India, and it contains 20% corosolic acid. Cells were treated with 50, 100, and 150 µg/ml of EBLE for 24 h, and cytotoxicity was evaluated by MTT assay. Apoptosis-related morphology was investigated by DAPI nuclear staining. Protein and gene expressions of p-Akt, FOXO1, p53, MDM2, p21, p27, CDK4, cyclin D1, and E1 were evaluated through Western blotting and qPCR. EBLE treatments caused significant, concentration-dependent cytotoxicity. DAPI staining and flow cytometry studies showed chromatin condensation, increased apoptotic cell population and cell cycle arrest at subG0/G1 phase upon EBLE treatments respectively. Furthermore, EBLE treatments significantly increased the expressions of p53, p21, p27, FOXO1, while p-Akt, MDM2, CDK4, cyclin D1, and E1 expressions were downregulated. These findings suggested that EBLE induces G1-phase of cell cycle arrest and apoptosis in HepG2 cells. EBLE may serve as a therapeutic agent against hepatocellular carcinoma.

Lagerstroemia speciosa (L.) Pers. triggers oxidative stress mediated apoptosis via intrinsic mitochondrial pathway in HepG2 cells.

Hepatocellular carcinoma is the second leading cause of cancer-related mortality worldwide. Lagerstroemia speciosa Pers. (Lythraceae) commonly known as Banaba has been used in different forms in traditional medicinal systems for treating various diseases which include diabetes and obesity. In this study, we investigated the cytotoxic potential of ethanolic Banaba leaf extract (EBLE) in HepG2 cells. The phytochemical analysis of EBLE was performed by HPTLC. HepG2 cells were treated with EBLE at 25, 50, 100, and 150 µg/mL concentrations, and cytotoxicity was evaluated by MTT assay. Oxidative stress was assessed by the evaluation of lipid peroxidation, superoxide dismutase, and reduced glutathione. Apoptosis-related morphology was investigated by acridine orange and ethidium bromide (AO/EB) dual staining. Mitochondrial membrane potential (ΔΨm) was evaluated by JC-1 staining. Apoptosis-related marker genes were evaluated by qPCR. HPTLC analysis confirmed the presence of corosolic acid (12.87 µg/mg), berberine (3.19 µg/mg), and gallic acid (2.94 µg/mg) in EBLE. EBLE treatments caused significant and concentration-dependent cytotoxicity and oxidative stress in HepG2 cells. Dual staining with AO/EB confirmed membrane distortion and nuclear chromatin condensation upon EBLE treatments. JC-I staining revealed the loss of ΔΨm. Furthermore, at a molecular level, EBLE treatments interfere with Bax/Bcl-2 homeostasis and induced the pro-apoptotic marker genes such as cytochrome c, Apaf-1, and caspases 9 and 3. EBLE treatments caused cytotoxicity in HepG2 cells, and this could be due to the induction of oxidative stress and apoptosis via the intrinsic or mitochondrial pathway.

The Structure of the Holo-Acyl Carrier Protein of Leishmania major Displays a Remarkably Different Phosphopantetheinyl Transferase Binding Interface.

The genome of Leishmania major encodes a type II fatty acid biosynthesis pathway for which no structural or biochemical information exists. Here, for the first time, we have characterized the central player of the pathway, the acyl carrier protein (LmACP), using nuclear magnetic resonance (NMR). Structurally, the LmACP molecule is similar to other type II ACPs, comprising a four-helix bundle, enclosing a hydrophobic core. Dissimilarities in sequence, however, exist in helix II (recognition helix) of the protein. The enzymatic conversion of apo-LmACP into the holo form using type I (Escherichia coli AcpS) and type II (Sfp type) phosphopantetheinyl transferases (PPTs) is relatively slow. Mutagenesis studies underscore the importance of the residues present at the protein-protein interaction interface of LmACP in modulating the activity of PPTs. Interestingly, the cognate PPT for this ACP, the L. major 4'-phosphopantetheinyl transferase (LmPPT), does not show any enzymatic activity toward it, though it readily converts other type I and type II ACPs into their holo forms. NMR chemical shift perturbation studies suggest a moderately tight complex between LmACP and its cognate PPT, suggesting inhibition. We surmise that the unique surface of LmACP might have evolved to complement its cognate enzyme (LmPPT), possibly for the purpose of regulation.

Lagerstroemia speciosa Pers. (Lythraceae) Ethanolic Extract Attenuates Isoniazid-Induced Oxidative Stress and Hepatic Inflammation in Rats.

Background Drug-induced liver injury is a common cause of acute liver failure. Isoniazid (INH) is used as a first-line treatment for tuberculosis. Clinical and experimental studies have reported abnormal liver function after INH therapy. Lagerstroemia speciosa Pers., commonly known as banaba, has been traditionally used to treat various ailments including diabetes and obesity due to its antioxidant and anti-inflammatory properties. Aim To investigate the hepatoprotective effect of ethanolic banaba leaf extract (EBLE) against INH-induced hepatotoxicity in rats. Materials and methods A total of 30 male Wistar albino rats (150 - 200 g) were divided into five groups (n = 6). Group I rats were served as a control and were administered dimethyl sulfoxide for the first 30 days and water for the next 30 consecutive days. Group II rats were administered INH (50 mg/kg, p.o.) once in the first 30 consecutive days and sacrificed at Day 30. Group III rats were administered INH for 30 consecutive days and left without treatment for the next 30 days. In Groups IV and V, rats were post-treated orally with EBLE 250 and 500 mg/kg, p.o. (0.3 ml/rat) for 30 days after INH administration. At the end of Day 60, the remaining group of animals were sacrificed. The blood and liver tissues were collected. The marker enzymes of hepatotoxicity, oxidative stress markers, inflammatory markers, and histopathology were analyzed. Results INH administration induced significant elevation of marker enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, bilirubin, gamma-glutamyl transpeptidase) of hepatotoxicity in the serum. This treatment also increased lipid peroxidation and proinflammatory marker expression (tumor necrosis factor-alpha, transforming growth factor-beta, and nuclear factor kappa B (NF-κB) except inhibitor of NF-κB) and decreased antioxidants such superoxide dismutase, catalase, and glutathione in the liver tissue. All these abnormalities were significantly mitigated after treatment with EBLE. Conclusion The results of this study suggest that EBLE can be used for INH-induced hepatotoxicity.

Epithelial mesenchymal transition induced nuclear localization of the extracellular matrix protein Fibronectin.

Fibronectin (FN), an extracellular matrix (ECM) glycoprotein, is a well-known marker for Epithelial Mesenchymal Transition (EMT). In the ECM, FN has been shown to form long fibrils and play critical roles in regulating cellular attachment and migration during EMT associated with physiological processes such as embryonic development, wound healing as well as pathological processes such as tissue fibrosis and cancer. Subsequently, the cytokine, Transforming Growth Factor ß (TGFß), an inducer of EMT, was found to induce FN expression in a c-Jun N-terminal kinase (JNK) dependent manner. Moreover, extracellular FN, by itself, was also shown to induce EMT in breast epithelial cells in serum-free condition. Collectively, all the literature published so far has shown and established the role of extracellular FN during EMT. In this report, we have shown that EMT induced entry of FN into the nucleus of mouse breast epithelial cells. To our knowledge, this is the first report showing nuclear localization of the extracellular matrix protein Fibronectin during EMT and thereby suggests a possible nuclear function for the ECM protein.

Synergy between human DNA ligase I and topoisomerase 1 unveils new therapeutic strategy for the management of colorectal cancer.

DNA topoisomerase 1 (Topo 1) is a pivotal player in various DNA processes, including replication, repair, and transcription. It serves as a target for anticancer drugs like camptothecin and its derivatives (Topotecan and SN-38/Irinotecan). However, the emergence of drug resistance and the associated adverse effects, such as alopecia, anemia, dyspnea, fever, chills, and painful or difficult urination, pose significant challenges in Topo 1-targeted therapy, necessitating urgent attention. Human DNA Ligase 1 (hLig I), recognized primarily for its role in DNA replication and repair of DNA breaks, intriguingly exhibits a DNA relaxation activity akin to Topo 1. This raised the hypothesis that hLig I might compensate for Topo 1 inhibition, contributing to resistance against Topo 1 inhibitors. To explore this hypothesis, we assessed the efficacy of hLig I inhibition alone and in combination with Topo 1 in cancer cells. As anticipated, the overexpression of hLig I was observed after Topo 1 inhibition in colorectal cancer cells, affirming our hypothesis. Previously identified as an inhibitor of hLig I's DNA relaxation activity, compound 27 (C 27), when combined with Topotecan, demonstrated a synergistic antiproliferative effect on colorectal cancer cells. Notably, cells with downregulated hLig I (via siRNA, inhibitors, or genetic manipulation) exhibited significantly heightened sensitivity to Topotecan. This observation strongly supports the concept that hLig I contribute to resistance against clinically relevant Topo 1 inhibitors in colorectal cancers. In conclusion, our findings offer evidence for the synergistic impact of combining hLig I inhibitors with Topotecan in the treatment of colorectal cancers, providing a promising strategy to overcome resistance to Topo 1 inhibitors.Communicated by Ramaswamy H. Sarma.

Assessment of radon transportation and uranium content in the tectonically active zone of Himalaya, India.

The study shows how geology and tectonic activity affect the soil gas 222Rn concentration. The tectonically active zone, namely the Ghuttu region, which is located within the Himalayan seismic belt, was studied to decipher its impact on soil gas 222Rn concentrations. A soil gas 222Rn study was performed in the soil at a depth of 30 cm, and it varied from 426 ± 156 Bq m-3 to 24,057 ± 1110 Bq m-3 with an average of 5356.5 ± 1634.6 Bq m-3, and at 60 cm below the soil surface, the concentration varied from 1130 ± 416 Bq m-3 to 30,236 ± 1350 Bq m-3 with an average of 8928.5 ± 2039.5 Bq m-3. These concentrations vary in soil from -3.4 % to 437.3 % as the depth moves from 30 cm to 60 cm. The variation in uranium content also shows anomalies, and higher values of uranium content in the soil affect the radon concentration in the study area. The average soil gas 222Rn concentration in the Ghuttu window was found to be higher than that in its surrounding region. This is likely due to transportation from daughter products of uranium. 222Rn mass exhalation rate measurements were also carried out, and a weak correlation with the soil gas 222Rn concentration was observed. A significant variation in the mass exhalation rate was noticed in tectonically active areas. This study is vital to understanding the behavior of radon and uranium in tectonic regions.

A study of 222Rn/220Rn exhalation rate and indoor 222Rn/220Rn levels in higher Himalayan terrain.

The noble radioactive gas radon and its isotope thoron dominate terrestrial radiation in the indoor environment. These gases eventually disintegrate generating radioactive ions that readily adhere to aerosol particles. This study was conducted in a tectonically active location with significant radon concentrations. The obtained average values of radon mass exhalation and thoron surface exhalation rate from this study are higher than the global average values of 56 mBq kg-1 h-1 and 1000 mBq m-2 s-1, respectively. As the exhalation rates are higher, naturally the average radon and thoron concentrations are also greater than the worldwide average values of 40 and 10 Bq m-3, respectively. No significant correlation was observed between 222Rn and 220Rn exhalation rate and indoor 222Rn/220Rn concentration. The exposure dose due to 222Rn, 220Rn and their progenies shows no significant health risk.

The apo-acyl coenzyme A binding protein of Leishmania major forms a unique 'AXXA' motif mediated dimer.

Acyl-Coenzyme A binding domain containing proteins (ACBDs) are ubiquitous in nearly all eukaryotes. They can exist as a free protein, or a domain of a large, multidomain, multifunctional protein. Besides modularity, ACBDs also display multiplicity. The same organism may have multiple ACBDs, differing in sequence and organization. By virtue of this diversity, ACBDs perform functions ranging from transport, synthesis, trafficking, signal transduction, transcription, and gene regulation. In plants and some microorganisms, these ACBDs are designated ACBPs (acyl-CoA binding proteins). The simplest ACBD/ACBP is a small, ∼10 kDa, soluble protein, comprising the acyl-CoA binding (ACB) domain. Most of these small ACBDs exist as monomers, while a few show a tendency to oligomerize. In sync with those studies, we report the crystal structure of two ACBDs from Leishmania major, named ACBP103, and ACBP96 based on the number of residues present. Interestingly, ACBP103 crystallized as a monomer and a dimer under different crystallization conditions. Careful examination of the dimer disclosed an exposed 'AXXA' motif in the helix I of the two ACBP103 monomers, aligned in a head-to-tail arrangement in the dimer. Glutaraldehyde cross-linking studies confirm that apo-ACBP103 can self-associate in solution. Isothermal titration calorimetry studies further show that ACBP103 can bind ligands ranging from C8 - to C20-CoA, and the data could be best fit to a 'two sets of sites'/sequential binding site model. Taken together, our studies show that Leishmania major ACBP103 can self-associate in the apo-form through a unique dimerization motif, an interaction that may play an important role in its function.

Precursor engineering for soft selective synthesis of phase pure metal-rich digenite (Cu9S5) and djurleite (Cu31S16) nanocrystals and investigation of their photo-switching characteristics.

Copper sulfide nanostructures have evolved as one of the most technologically important materials for energy conversion and storage owing to their economic and non-toxic nature and superior performances. This paper presents a direct, scalable synthetic route aided by a single source molecular precursor (SSP) approach to access copper sulfide nanomaterials. Two SSPs, CuX(dmpymSH)(PPh3)2 (where X = Cl or I), were synthesized in quantitative yields and thermolyzed under appropriate conditions to afford the nanostructures. The analysis of the nanostructures through pXRD, EDS and XPS suggested that phase pure digenite (Cu9S5) and djurleite (Cu31S16) nanostructures were isolated from -Cl and -I substituted SSPs, respectively. The morphologies of the as-synthesized nanomaterials were investigated using electron microscopy techniques (SEM and TEM). DRS studies on pristine materials revealed blue shifted optical band gaps, which were found to be optimum for photoelectrochemical application. A prototype photoelectrochemical cell fabricated using the pristine nanostructures exhibited a stable photo-switching property, which presents these materials as suitable economic and environmentally friendly photon absorber materials.

Measurement of indoor radioactivity and dose derived from 222Rn, 220Rn and EECs by using SSNTD based technique.

Alpha flux radiated from 222Rn, 220Rn and progeny is the primary contributor of natural radioactivity to the inhabitants in the ambient atmosphere. The annual indoor 222Rn and 220Rn concentrations were found to be 85 ± 43 and 84 ± 36 Bq m-3, respectively. The estimated annual indoor 222Rn and 220Rn concentration is below to reference value of 100 Bq m-3 suggested by WHO. The calculated annual inhalation dose due to exposure to the alpha flux of 222Rn, 220Rn and their progeny is well below the recommended reference level given by UNSCEAR and ICRP. The data were further checked for normalisation and found that 222Rn and Effective Equilibrium Radon Concentration (EERC) data are not normally distributed.

Customizing Treatment Scheduling Windows with a Time Margin Recipe: A Single-institutional Study.

Purpose: Rising cancer incidences, complex treatment techniques, and workflows have all impacted the radiotherapy scheduling process. Intelligent appointment scheduling is needed to help radiotherapy users adapt to new practices. Materials and Methods: We utilized van Herk's safety margin formula to determine the radiotherapy department's treatment scheduling window (TSW). In addition, we examined the influence of in-room imaging on linac occupancy time (LOT). Varian Aria™ software version 15.1 was used to collect retrospective data on LOT, treatment site, intent, techniques, special protocol, and in-room imaging. Results: Treatment scheduling windows varied across treatment sites. The mean TSW using van Herk's formalism was 31.5 min, significantly longer than the current TSW of 15 min (P = 0.036), with the pelvic site having the longest (43.8 min) and the brain site having the shortest (12 min). 28% of patients exceeded the in-practice TSW of 15 min. 46.2% of patients had multiple images per fraction, with the proportion being highest in pelvic patients (33%). Patients treated with palliative intent, intensity-modulated radiotherapy, special protocols (bladder protocol and gating), and multiple in-room images per fraction had significantly higher LOT. High treatment time uncertainty was observed in the pelvic and thorax sites, indicating the impact of in-room imaging frequency and on-couch treatment decisions on overall treatment time and indicating that current treatment practices should be reviewed and modified if necessary. Conclusions: The time margin recipe can customize the treatment scheduling window and improve treatment practices. This formalism can help manage the radiotherapy department's workload and reduce patient wait times.

Efficient and Reliable Data Extraction in Radiation Oncology using Python Programming Language: A Pilot Study.

Background and Purpose: In recent years, data science approaches have entered health-care systems such as radiology, pathology, and radiation oncology. In our pilot study, we developed an automated data mining approach to extract data from a treatment planning system (TPS) with high speed, maximum accuracy, and little human interaction. We compared the amount of time required for manual data extraction versus the automated data mining technique. Materials and Methods: A Python programming script was created to extract specified parameters and features pertaining to patients and treatment (a total of 25 features) from TPS. We successfully implemented automation in data mining, utilizing the application programming interface environment provided by the external beam radiation therapy equipment provider for the whole group of patients who were accepted for treatment. Results: This in-house Python-based script extracted selected features for 427 patients in 0.28 ± 0.03 min with 100% accuracy at an astonishing rate of 0.04 s/plan. Comparatively, manual extraction of 25 parameters took an average of 4.5 ± 0.33 min/plan, along with associated transcriptional and transpositional errors and missing data information. This new approach turned out to be 6850 times faster than the conventional approach. Manual feature extraction time increased by a factor of nearly 2.5 if we doubled the number of features extracted, whereas for the Python script, it increased by a factor of just 1.15. Conclusion: We conclude that our in-house developed Python script can extract plan data from TPS at a far higher speed (>6000 times) and with the best possible accuracy compared to manual data extraction.

Evaluation of the Ethanolic Leaf Extract of Abutilon indicum on Isonicotinic Acid Hydrazide-Induced Proinflammatory Marker Gene Expression Changes.

BACKGROUND: Abutilon indicum, widely found in India, Sri Lanka, and parts of America and Malaysia, is renowned for its rich bioactive compounds including alkaloids, flavonoids, and sesquiterpene lactones. Due to its diverse pharmacological potential, it has garnered significant attention in traditional medicine. In particular, the ethanolic leaf extract of Abutilon indicum (ELEAI) has demonstrated anti-inflammatory effects, notably targeting the 5-lipoxygenase enzyme pivotal in inflammatory responses. OBJECTIVE: This study aimed to elucidate the impact of the ELEAI on proinflammatory marker gene expression induced by isoniazid (INH). METHODS: A total of 36 rats were systematically divided into six experimental groups. The control group received DMSO orally for the initial 30 days followed by distilled water for the subsequent 30 days. The INH group received a daily dose of INH (30 mg/kg b.w., i.p.) for 30 days and the rats were then sacrificed on day 30. The ELEAI (250 mg/kg) group was administered INH daily for 30 days, followed by daily post-treatment with ELEAI (250 mg/kg) for another 30 days. Similarly, the ELEAI (500 mg/kg) group received INH daily for 30 days, followed by daily post-treatment with ELEAI (500 mg/kg) for another 30 days. The silymarin (SIL) group was given INH daily for 30 days, followed by post-treatment with SIL at a dose of 100 mg/kg body weight daily for the subsequent 30 days. Finally, the ELEAI (500 mg/kg) alone group was administered distilled water orally for the first 30 days and then received ELEAI at a dose of 500 mg/kg b.w. orally once daily for the next 30 days. RESULTS: Continuous INH exposure for a month led to a pronounced increase in proinflammatory genes like TNF-α, TGF-ß, and NF-kB and a decrease in the IkB gene in rat liver tissues. Subsequent treatment with SIL (100 mg/kg) and ELEAI (250 and 500 mg/kg) post-INH exposure resulted in a marked decrease in proinflammatory genes and a surge in IkB expression. CONCLUSION: The findings suggest that the ELEAI exerts a dose-responsive influence on proinflammatory activities. Notably, A. indicum counteracts inflammation, especially that triggered by bradykinin and prostaglandins. The ELEAI showcases promising therapeutic potential, exhibiting both pro and anti-inflammatory properties and antiproliferative characteristics.

Effectiveness of electrical vestibular nerve stimulation as adjunctive therapy to improve the cognitive functions in patients with Parkinson's disease.

OBJECTIVES: The present study was undertaken to observe the effectiveness of electrical vestibular stimulation in improving cognitive functions in patients with Parkinson's disease. METHODS: Randomized controlled trial (ClinicalTrials.gov Identifier: NCT04450550). 30 cases of PD, including both males and females were recruited in the study by convenient sampling after obtaining written informed consent. After recruiting, the participants were randomly assigned into two groups. The control group (n=15) received placebo stimulation whereas the intervention group (n=15) received electrical vestibular stimulation administered for 12 weeks. Auditory, visual reaction time and spatial and verbal memory were recorded before and after 6 weeks and after 12 weeks of intervention and compared. RESULTS: There was a significant improvement in both auditory and visual reaction time of right and left-hand responses. Also, significant improvement was observed in both the spatial and verbal memory of the patients. CONCLUSIONS: There was a significant improvement in the auditory and visual reaction time and spatial and verbal memory in the participants after the electrical vestibular nerve stimulation administration. No side effects were reported by the study participants and they have expressed willingness to continue the intervention after the study period also. The study recommends further detailed studies with a higher sample size to adopt electrical vestibular nerve stimulation as adjunctive therapy in the management of Parkinson's disease.

Controlled synthesis of photoresponsive bismuthinite (Bi2S3) nanostructures mediated through a new 1D bismuth-pyrimidylthiolate coordination polymer as a molecular precursor.

Bismuthinite (Bi2S3) nanostructures have garnered significant interest due to their appealing photoresponsivity which has positioned them as an attractive choice for energy conversion applications. However, to utilize their full potential, a simple and economically viable method of preparation is highly desirable. Herein, we present the synthesis and characterization including structural elucidation of a new air- and moisture-stable bismuth-pyrimidylthiolate complex. This complex serves as an efficient single-source molecular precursor for the facile preparation of phase-pure Bi2S3 nanostructures. Powder X-ray diffraction (PXRD), Raman spectroscopy, electron dispersive spectroscopy (EDS) and electron microscopy techniques were used to assess the crystal structure, phase purity, elemental composition and morphology of the as-prepared nanostructures. This study also revealed the profound effects of temperature and growth duration on the crystallinity, phase formation and morphology of nanostructures. The optical band gap of the nanostructures was tuned within the range of 1.9-2.3 eV, which is blue shifted with respect to the bulk bandgap and suitable for photovoltaic applications. Liquid junction photo-electrochemical cells fabricated from the as-prepared Bi2S3 nanostructure exhibit efficient photoresponsivity and good photo-stability, which project them as promising candidates for alternative low-cost photon absorber materials.

Effectiveness of electrical vestibular nerve stimulation on the range of motion in patients with Parkinson's disease.

OBJECTIVES: The present study was undertaken to observe the effectiveness of electrical vestibular stimulation on the range of motion (ROM) in patients with Parkinson's disease (PD). METHODS: The present study was a randomized controlled trial (ClinicalTrials.gov Identifier: NCT04450550). The study participants were assessed at three points of time. After recording baseline cognitive functions, electrical vestibular nerve stimulation was administered to the intervention group and placebo stimulation was administered to the control group for 12 weeks. Post-intervention parameters were recorded after 6 weeks and after 12 weeks after the intervention in both control and intervention groups. A total of 30 cases of PD, including both males and females were recruited in the study by convenient sampling after obtaining written informed consent. All ROM and flexibility measurements were recorded using a universal goniometer and standard protocol with help of an experienced physiotherapist at our hospital. RESULTS: There was a significant improvement in the hip internal and external rotation right and left sides. There was a significant improvement in the hip extension right and left. There was a significant improvement in the ankle plantarflexion left and ankle dorsiflexion right and left followed by the intervention. There was a significant decline in the hip internal rotation on right and left sides. There was a significant decline in the hip extension and ankle dorsiflexion on the left side. CONCLUSIONS: The study results confirm the improvement of motor activities of patients with PD followed by vestibular stimulation. Further detailed studies are recommended to support the application of vestibular stimulation as an alternative therapy in the management of motor functions in patients with PD.

Donor-Derived Cell-Free DNA as a Non-Invasive Biomarker for Graft Rejection in Kidney Transplant Recipients: A Prospective Study among the Indian Population.

Monitoring graft health and detecting graft rejection is crucial for the success of post-transplantation outcomes. In Western countries, the use of donor-derived cell-free DNA (dd-cfDNA) has gained widespread recognition as a diagnostic tool for kidney transplant recipients. However, the role of dd-cfDNA among the Indian population remains unexplored. The recipients were categorized into two groups: the post-transplant recipient (PTR) group (n = 16) and the random recipient (RR) group (n = 87). Blood samples were collected daily from the PTR group over a 7-day period, whereas the RR group's samples were obtained at varying intervals. In this study, we used a targeted approach to identify dd-cfDNA, which eliminated the need for genotyping, and is based on the minor allele frequency of SNP assays. In the PTR group, elevated dd-cfDNA% levels were observed immediately after transplantation, but returned to normal levels within five days. Within the RR group, heightened serum creatinine levels were directly proportional to increased dd-cfDNA%. Sixteen recipients were advised to undergo biopsy due to elevated serum creatinine and other pathological markers. Among these sixteen recipients, six experienced antibody-mediated rejection (ABMR), two exhibited graft dysfunctions, two had active graft injury, and six (37.5%) recipients showed no rejection (NR). In cases of biopsy-proven ABMR and NR, recipients displayed a mean ± SD dd-cfDNA% of 2.80 ± 1.77 and 0.30 ± 0.35, respectively. This study found that the selected SNP assays exhibit a high proficiency in identifying donor DNA. This study also supports the use of dd-cfDNA as a routine diagnostic test for kidney transplant recipients, along with biopsies and serum creatinine, to attain better graft monitoring.