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Abstract Background Cardiac disease in pregnancy is a major contributor to maternal mortality in high, middle and low-income countries. Availability of data on outcomes of pregnancy in women with heart disease is important for planning resources to reduce maternal mortality. Prospective data on outcomes and risk predictors of mortality in pregnant women with heart disease (PWWHD) from low- and middle-income countries are scarce. Methods The Tamil Nadu Pregnancy and Heart Disease Registry (TNPHDR) is a prospective, multicentric and multidisciplinary registry of PWWHD from 29 participating sites including both public and private sectors, across the state of Tamil Nadu in India. The TNPHDR is aimed to provide data on incidence of maternal and fetal outcomes, adverse outcome predictors, applicability of the modified World Health Organization (mWHO) classification of maternal cardiovascular risk and the International risk scoring systems (ZAHARA and CARPREG I & II) in Indian population and identify possible gaps in the existing management of PWWHD. Pregnancy and heart teams will be formed in all participating sites. Baseline demographic, clinical, laboratory and imaging parameters, data on counselling received, antenatal triage and management, peripartum management and postpartum care will be collected from 2500 eligible participants as part of the TNPHDR. Participants will be followed up at one, three and six-months after delivery/termination of pregnancy to document study outcomes. Predictors of maternal and foetal outcome will be identified. Discussion The TNPHDR will be the first representative registry from low- and middle-income countries aimed at providing crucial information on pregnancy outcomes and risk predictors in PWWHD. The results of TNPHDR could help to formulate steps for improved care and to generate a customised and practical guideline for managing pregnancy in women with heart disease in limited resource settings. Trial registration The TNPHDR is registered under Clinical Trials Registry-India ( CTRI/2020/01/022736 ).

Rare eye diseases (REDs) are mostly progressive and are the leading cause of irreversible blindness. The disease onset can vary from early childhood to late adulthood. A high rate of consanguinity contributes to India's predisposition to RED. Most gene variations causing REDs are monogenic and, in some cases, digenic. All three types of Mendelian inheritance have been reported in REDs. Some of the REDs are related to systemic illness with variable phenotypes in affected family members. Approximately, 50% of the children affected by REDs show associated phenotypes at the early stages of the disease. A precise clinical diagnosis becomes challenging due to high clinical and genetic heterogeneity. Technological advances, such as next-generation sequencing (NGS), have improved genetic and genomic testing for REDs, thereby aiding in determining the underlying causative gene variants. It is noteworthy that genetic testing together with genetic counseling facilitates a more personalized approach in the accurate diagnosis and management of the disease. In this review, we discuss REDs identified in the Indian population and their underlying genetic etiology.

To alleviate the problem, a new and unique property for the complex is desirable. Novel hexagonal stratified structures have been observed. This category of hybrid material is prepared with surfactant, polyoxometalate and s-triazine complex through ionic interaction. To know the tenacity of the present study for an inventive property was further studied. A novel technique of shock wave impulsed material was developed in this work; employed to fabricate the FO TFN membrane. The experimental results recommended that notable attention should be paid to the 0.1 wt % POM-AG incorporated TFN membrane which exhibits 9.2 LMH higher pure water flux compared to the composite membranes without shock imposed material incorporation that were synthesized. Those water enhancements of FO membranes could be assigned the presence of the POM-AG, which is allocated evenly throughout the PA active layer. Thus, the formation of porous selective layer is minimized water transport resistance. The dielectric and conduction mechanisms were monitored through dielectric anomalies and intramolecular charge transfer of the covalence of Mo-O and NH+, manifested by dipolar relaxation. An unassociated in intensity originated from the differential of the selective orientation during the analyses of the experimental data for the powder samples. Furthermore, the structural, morphological and thermal properties of hock wave impulsed hybrid material have been investigated using XRD, SEM, FT-IR, TGA, and NMR techniques. However, the FO membrane biological activity was reported above 70%.

This paper demonstrates a concept of split domination in neutrosophic graphs.Minimal split domination, lower and upper split dominations in neutrosophic graphs are discussed. Theorems are derived for minimal split domination in neutrosophic graphs with suitable examples.

Mohd Nasarudin Watroly,1 Mahendran Sekar,1 Shivkanya Fuloria,2 Siew Hua Gan,3 Srikanth Jeyabalan,4 Yuan Seng Wu,5,6 Vetriselvan Subramaniyan,7 Kathiresan V Sathasivam,8 Subban Ravi,9 Nur Najihah Izzati Mat Rani,10 Pei Teng Lum,1 Jaishree Vaijanathappa,11 Dhanalekshmi Unnikrishnan Meenakshi,12 Shankar Mani,13 Neeraj Kumar Fuloria2 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia; 2Faculty of Pharmacy & Centre of Excellence for Biomaterials Engineering, AIMST University, Kedah, 08100, Malaysia; 3School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan, 47500, Malaysia; 4Department of Pharmacology, Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research (DU), Chennai, Tamil Nadu, 600116, India; 5Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Selangor, 47500, Malaysia; 6Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Selangor, 47500, Malaysia; 7Faculty of Medicine, Bioscience and Nursing, MAHSA University, Selangor, 42610, Malaysia; 8Faculty of Applied Science & Centre of Excellence for Biomaterials Engineering, AIMST University, Kedah, 08100, Malaysia; 9Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, 640 021, India; 10Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia; 11Department of Pharmaceutical Chemistry, School of Life Sciences, JSS Academy of Higher Education and Research Mauritius, Vacoas, Mauritius; 12College of Pharmacy, National University of Science and Technology, Muscat, 130, Oman; 13Department of Pharmaceutical Chemistry, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Mandya, Karnataka, 571418, IndiaCorrespondence: Neeraj Kumar Fuloria; Shivkanya FuloriaFaculty of Pharmacy & Centre of Excellence for Biomaterials Engineering, AIMST University, Kedah, 08100, MalaysiaTel +60 16 4037685; +60 14 3034057Email neerajkumar@aimst.edu.my; shivkanya_fuloria@aimst.edu.myAbstract: Anthraquinones (AQs) are found in a variety of consumer products, including foods, nutritional supplements, drugs, and traditional medicines, and have a wide range of pharmacological actions. Rubiadin, a 1,3-dihydroxy-2-methyl anthraquinone, primarily originates from Rubia cordifolia Linn (Rubiaceae). It was first discovered in 1981 and has been reported for many biological activities. However, no review has been reported so far to create awareness about this molecule and its role in future drug discovery. Therefore, the present review aimed to provide comprehensive evidence of Rubiadin’s phytochemistry, biosynthesis, physicochemical properties, biological properties and therapeutic potential. Relevant literature was gathered from numerous scientific databases including PubMed, ScienceDirect, Scopus and Google Scholar between 1981 and up-to-date. The distribution of Rubiadin in numerous medicinal plants, as well as its method of isolation, synthesis, characterisation, physiochemical properties and possible biosynthesis pathways, was extensively covered in this review. Following a rigorous screening and tabulating, a thorough description of Rubiadin’s biological properties was gathered, which were based on scientific evidences. Rubiadin fits all five of Lipinski’s rule for drug-likeness properties. Then, the in depth physiochemical characteristics of Rubiadin were investigated. The simple technique for Rubiadin’s isolation from R. cordifolia and the procedure of synthesis was described. Rubiadin is also biosynthesized via the polyketide and chorismate/o-succinylbenzoic acid pathways. Rubiadin is a powerful molecule with anticancer, antiosteoporotic, hepatoprotective, neuroprotective, anti-inflammatory, antidiabetic, antioxidant, antibacterial, antimalarial, antifungal, and antiviral properties. The mechanism of action for the majority of the pharmacological actions reported, however, is unknown. In addition to this review, an in silico molecular docking study was performed against proteins with PDB IDs: 3AOX, 6OLX, 6OSP, and 6SDC to support the anticancer properties of Rubiadin. The toxicity profile, pharmacokinetics and possible structural modifications were also described. Rubiadin was also proven to have the highest binding affinity to the targeted proteins in an in silico study; thus, we believe it may be a potential anticancer molecule. In order to present Rubiadin as a novel candidate for future therapeutic development, advanced studies on preclinical, clinical trials, bioavailability, permeability and administration of safe doses are necessary.Keywords: Rubiadin, Rubia cordifolia, biosynthesis, physicochemical properties, anticancer, pharmacology

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Abstract Background India accounts for 20% of the global retinoblastoma (RB) burden. However, the existing data on RB1 gene germline mutations and its influence on clinical decisions is minimally explored. Methods Fifty children with RB underwent complete clinical examination and appropriate multidisciplinary management. Screening of germline RB1 gene mutations was performed through next-generation sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The mutation and non-mutation groups were compared for clinical parameters especially severity, progression and recurrence. Results Twenty-nine patients had bilateral RB (BLRB) and 21 had unilateral RB (ULRB). The genetic analysis revealed 20 RB1 variations in 29 probands, inclusive of 3 novel mutations, known 16 mutations and heterozygous whole gene deletions. The mutation detection rate (MDR) was 86.2% in BLRB and 19% in ULRB. Associations of disease recurrence (p = 0.021), progression (p = 0.000) and higher percentage of optic nerve invasion, subretinal seeds and high-risk pathological factors were observed in the mutation group. Clinical management was influenced by the presence of germline mutations, particularly while deciding on enucleation, frequency of periodic follow up and radiotherapy. Conclusions We identified novel RB1 mutations, and our mutation detection rate was on par with the previous global studies. In our study, genetic results influenced clinical management and we suggest that it should be an essential and integral component of RB-care in India and elsewhere.

Obsessive-compulsive disorder (OCD) is a chronic and complex psychiatric disorder that usually includes both obsessions and compulsions. Morinda citrifolia L. (Noni) is a functional food and it is a well-known plant due to its potential therapeutic effects on human health in many disorders including neurological and neurodegenerative diseases. The purpose of this study was to evaluate the potential effect of M. citrifolia fruits extract (MCFE) against obsessive-compulsive disorder using the marble burying and nestlet shredding behavior mice models. In addition, brain neurotransmitters such as dopamine (DA), serotonin and noradrenaline (NA) were also assessed. Five mice were placed in each of the different groups, and the treatment was given to the animals for a period of 15 days. The marble burying test was evaluated for 30 min on days 1, 7, and 14 while the nestlet shredding test was evaluated for 60 min on days 2, 8, and 15. Treatments with MCFE (100 and 200 mg/kg, p.o.) significantly improved in both behavior tasks when compared to the control group. In addition, diazepam (2 mg/kg, i.p.) and fluoxetine (15 mg/kg, p.o.) were also significantly improved in both tasks when compared with the control mice. Further locomotor activity study revealed that MCFE and fluoxetine did not affect the locomotor functions when compared to vehicle treated mice. In contrast, diazepam significantly decreased locomotion when compared to the control group. The significant amelioration of biogenic amines were observed in the MCFE-treated animals with increased serotonin levels. The histopathology of the brain, liver, and kidney tissues after MCFE administration revealed normal morphological structure with no signs of toxicity or abnormalities. All these results together suggest that MCFE can be a potential drug candidate for the treatment of OCD. Future research should focus on theidentification and the anti-compulsive activity of the constituents from M. citrifolia.

The rate of breast cancer is rapidly increasing and discovering medications with therapeutic effects play a significant role in women’s health. Drugs derived from marine sponges have recently received FDA approval for the treatment of malignant tumors, including metastatic breast cancer. Spirastrella pachyspira (marine sponge) is mainly obtained from the western coastal region of India, and its anticancer potential has not been explored. Hence, the present study aimed to evaluate the anticancer potential of Spirastrella pachyspira extracts and its bioactive molecule sphingosine. The extracts were prepared using hexane, chloroform, ethyl acetate, and ethanol. The cytotoxic potential of the extracts were determined by an in-vitro MTT assay using SK-BR-3 cancer cell line. Subsequently, acute toxicity investigation was conducted in Swiss albino mice. Then, the anticancer effects of the extract was investigated in a xenograft model of SK-BR-3 caused breast cancer. DAPI staining was used to assess the extract’s ability to induce apoptosis. In addition, in-silico study was conducted on sphingosine with extracellular site of HER2. The ethyl acetate extract of Spirastrella pachyspira (IC50: 0.04 µg/ml) showed comparable anticancer effects with standard doxorubicin (IC50: 0.054 µg/ml). The LD50 of the extracts in acute toxicity testing was fund to be 2000 mg/kg b.wt. The survival index of mice in ethanol extract was 83.33%, whereas that of standard doxirubicin was 100%, indicating that ethyl acetate extract Spirastrella pachyspira has good antiproliferative/cytotoxic properties. The results were well comparable with standard doxorubicin. Further, the docking studies of sphingosine against HER2 demonstrated that the bioactive molecule engage with the extracellular region of HER2 and block the protein as also shown by standard trastuzumab. The findings of this research suggest that Spirastrella pachyspira and sphingosine may be potential candidate for the treatments of breast cancer, particularly for HER2 positive cells. Overall, the present results demonstrate that sphingosine looks like a promising molecule for the development of new drugs for the treatment of cancer. However, in order to carefully define the sphingosine risk-benefit ratio, future research should focus on evaluating in-vivo and clinical anticancer studies. This will involve balancing both their broad-spectrum effectiveness and their toxicity.

Macular corneal dystrophy (MCD) an autosomal recessive disorder leading to severe visual impairment is caused by mutations in the carbohydrate sulfotransferase 6 (CHST6) gene. Here, we describe generation of a iPSC line from peripheral blood mononuclear cells (PBMCs) from a 38 year old MCD patient harboring a homozygous mutation, p.V172L in the CHST6 gene. The iPSC line GLNNFi001-A was generated using an integration-free Sendai virus containing (KLF4, c-MYC, OCT4 and SOX2).

Membranous nephropathy (MN) is the most common cause of primary nephrotic syndrome among adults. The identification of phospholipase A2 receptor (PLA2R) as target antigen in most patients changed the management of MN dramatically, and provided a rationale for B-cell depleting agents such as rituximab. The efficacy of rituximab in inducing remission has been investigated in several studies, including 3 randomized controlled trials, in which complete and partial remission of proteinuria was achieved in approximately two-thirds of treated patients. Due to its favorable safety profile, rituximab is now considered a first-line treatment option for MN, especially in patients at moderate and high risk of deterioration in kidney function. However, questions remain about how to best use rituximab, including the optimal dosing regimen, a potential need for maintenance therapy, and assessment of long-term safety and efficacy outcomes. In this review, we provide an overview of the current literature and discuss both strengths and limitations of “the new standard.”