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5q14.3 microdeletion syndrome is a rare condition involving multiple genes such as MEF2C and RASA1 and is potentially classified as a neurocutaneous syndrome. Deletion of the MEF2C gene accounts for the majority of clinical manifestations, including global developmental delay, intellectual disability, seizures, and behavioral disorders. RASA1 deletion is linked to capillary malformations with arteriovenous malformations (CM-AVM). Until now, only 17 cases have been described with deletions of both genes. We present the first case described in Spain with the microdeletion in the 5q14.3 cytoband simultaneously affecting both MEF2C and RASA1, exhibiting the typical manifestations of this entity, and review the published cases to date.
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Although many genetic etiologies, such as Fanconi anemia, Shwachman-Diamond syndrome, dyskeratosis congenita, and Diamond-Blackfan anemia, from hereditary bone marrow failure are known today, the responsible gene remains unknown in a significant part of these patients. A 6-year-old girl, whose parents were first-cousin consanguineous, was referred to the pediatric hematology department due to growth retardation, thrombocytopenia, neutropenia, and anemia. The patient had low-set ears, pectus excavatum inferiorly, and cafe-au-lait spots. In whole-exome analysis, p.K385T (c.1154A > C) variant in the RASA3 gene was detected as homozygous. The amino acid position of the alteration is located in the conserved and ordered region, corresponding to the Ras GTPase activation domain (Ras-GAP) in the center of the protein. Importantly, most of in silico prediction tools of pathogenicity predicts the variant as damaging. RASopathies, which are characterized by many common clinical findings, such as atypical facial features, growth delays, and heart defects, are a group of rare genetic diseases caused by mutations in the genes involved in the Ras-MAPK pathway. The findings in this patient were consistent with the RASopathy-like phenotype and bone marrow failure. Interestingly, enrichment of RASopathy genes was observed in the RASA3 protein-protein interaction network. Furthermore, the subsequent topological clustering revealed a putative function module, which further implicates RASA3 in this disease as a novel potential causative gene. In this context, the detected RASA3 mutation could be manifesting itself clinically as the observed phenotype by disrupting the functional cooperation between the RASA3 protein and its interaction partners. Relatedly, current literature also supports the obtained findings. Overall, this study provides new insights into RASopathy and put forward the RASA3 gene as a novel candidate gene for this disease group.
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Diabetic cardiomyopathy (DCM) is one of the serious complications of type 2 diabetes mellitus. Vasant Kusumakar Rasa (VKR) is a Herbo-metallic formulation reported in Ayurveda, an Indian system of medicine. The present work was designed to study the effect of VKR in cardiomyopathy in type 2 diabetic rats. Diabetes was induced by feeding a high-fat diet (HFD) for 2 weeks followed by streptozotocin (STZ) administration (35 mg/kg i.p.). VKR was administered orally at dose of 28 and 56 mg/kg once a day for 16 weeks. The results of the study indicated that VKR treatment significantly improved the glycemic and lipid profile, serum insulin, CK-MB, LDH, and cardiac troponin-I when compared to diabetic control animals. VKR treatment in rats significantly improved the hemodynamic parameters and cardiac tissue levels of TNF-α, IL-1ß, and IL- 6 were also reduced. Antioxidant enzymes such as GSH, SOD, and catalase were improved in all treatment groups. Heart sections stained with H & E and Masson's trichome showed decreased damage to histoarchitecture of the myocardium. Expression of PI3K, Akt, and GLUT4 in the myocardium was upregulated after 16 weeks of VKR treatment. The study data suggested the cardioprotective capability of VKR in the management of diabetic cardiomyopathy in rats.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Cardiomiopatías Diabéticas , Estrés Oxidativo , Animales , Cardiomiopatías Diabéticas/prevención & control , Cardiomiopatías Diabéticas/fisiopatología , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/patología , Cardiomiopatías Diabéticas/tratamiento farmacológico , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Masculino , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Miocardio/patología , Miocardio/metabolismo , Antioxidantes/farmacología , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Biomarcadores/sangre , Medicina Ayurvédica , Ratas , Mediadores de Inflamación/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Citocinas/metabolismo , Transducción de SeñalRESUMEN
RASopathies encompass a diverse set of disorders affecting genes that encode proteins within the RAS-MAPK pathway. RASA1 mutations are the cause of an autosomal dominant disorder called capillary malformation-arteriovenous malformation type 1 (CM-AVM1). Unlike other RASopathies, facial dysmorphism has not been described in these patients. We phenotypically delineated a large family of individuals with multifocal fast-flow capillary malformations, severe lymphatic anomalies of perinatal onset, and dysmorphic features not previously described. Sequencing studies were performed on probands and related family members, confirming the segregation of dysmorphic features in affected members of a novel heterozygous variant in RASA1 (NM_002890.3:c.2366G>A, p.(Arg789Gln)). In this work, we broaden the phenotypic spectrum of CM-AVM type 1 and propose a new RASA1 variant as likely pathogenic.
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BACKGROUND: Herbo-mineral-metallic formulations are an inseparable part of the Ayurveda system of traditional medicine. Hridayarnava Rasa (HR) is a preparation containing metals like copper, sulphur, and mercury in processed forms and other herbs that do not produce toxic effects and adverse drug reactions when taken in appropriate dosage. Ayurveda practitioners use it in treating cardiac diseases like hypertension, cardiotoxicity and many more. The rasa-aushadhis possess characteristics such as rapid efficacy, little dosage required, and extensive therapeutic applicability. Hridayarnava Rasa [AFI Part-1, 20:55] has been employed for the treatment of various diseases from ancient times. A systematic study of these formulations manufacturing is required to maintain their quality, safety, and efficacy is a need of time to protect the immense faith of patients in Ayurveda. OBJECTIVES: The present study aimed to prepare HR as per standard operating procedures mentioned in the classical text and to characterize it physio-chemically using advanced analytical techniques. MATERIALS AND METHODS: HR was prepared and physicochemical analyses and assay of elements by ICP-AES were carried out as per Ayurvedic Pharmacopoeia of India (API). Powder X-ray diffraction (XRD), Field emission gun scanning electron microscopy with energy dispersive spectroscopy (FEG SEM, EDAX), CHNS-O analysis, Fourier Transform Infrared Spectroscopy (FTIR), Thermo-gravimetric analysis (TGA), Particle size distribution analysis (PSD) was carried out. RESULTS: The XRD analysis of HR showed the presence of unreacted sulphur and sulfides of copper and mercury. FEG SEM revealed the particles in the form of aggregates as nanocrystallites in the range of 100-1000 nm. Elemental analysis showed the presence of copper, sulphur, and mercury in major, along with traces of iron, calcium, sodium, potassium, and magnesium. In FTIR analysis, 18 peaks were observed, which strongly suggests the presence of various organic groups. In the TGA, four peaks were seen, which can be attributed to sulphur volatilization and oxidative changes in mercury. In PSD analysis, 50% of the material was found below 16.40 µm. CONCLUSION: To establish a piece of fundamental knowledge and ensure uniformity of these rasa-aushadhis, it is imperative to conduct an analysis of their characteristics as per classical texts and modern analytical techniques. Additionally, it is crucial to investigate the significance of each procedural step included in the preparation process. The inferences drawn are helpful as an essential aid for quality assurance and standardization of this herbo-mineral-metallic formulation.
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BACKGROUND: Hereditary pancreatitis (HP) is a chronic and recurrent inflammatory disorder caused by genetic abnormalities, often accompanied by severe symptoms and complications. Conventional treatments offer limited relief but fail to halt disease progression. An Ayurvedic Treatment Protocol has been reported to be effective in treating various types of pancreatitis. OBJECTIVES: This observational clinical study is aimed at assessing the efficacy of a year long Ayurvedic treatment protocol (ATP) in mitigating attack frequency and intensity in Hereditary Pancreatitis patients. MATERIALS & METHODS: The study enrolled 151 patients across diverse age groups and genders, subjecting them to a comprehensive Ayurvedic treatment protocol at a specialized center. The protocol incorporated Metal-Based Ayurvedic Formulation (MBAF) named Amar, alongside supportive Ayurvedic compounds and dietary adjustments. Patients underwent pre- and post-treatment evaluations involving interviews, medical records, blood tests, radiological imaging, and symptom assessments. Notably, pancreatic enzyme use was discontinued prior to initiating Ayurvedic treatment. RESULTS: Among 151 patients, 88 completed the year long ATP, resulting in significant enhancement of their quality of life. There was a marked 98.7% reduction in emergency hospitalizations and a notable 92.8% decrease in attack frequency (p < 0.0001). Radiological assessments indicated pancreatic health stabilization, while no adverse effects were reported, highlighting the intervention's safety and tolerability. CONCLUSION: The study furnishes promising evidence supporting the efficacy and safety of ATP, especially the MBAF, in managing Hereditary Pancreatitis. The observed decline in attack frequency, absence of adverse effects, and stabilization of pancreatic health underscore the potential of Ayurvedic medicine. Subsequent research, including randomized controlled trials, is warranted to substantiate these findings and elucidate underlying mechanisms.
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Sandy coastal areas are very dynamic systems in which morphological changes occur over different time scales from hours to decades. However, it has been widely reported that major storms are the main responsible of the most significant changes in short to medium time scales. Major storms have been defined using a variety of environmental variables, but they are normally associated with high values of wave height, duration, return period and direction. Here, we aim to characterize types of major storms and to categorize associated morphological impacts over a complex coastal system. The study site, known as Punta Rasa, is located in the Samborombón bay in the outer part of the Río de La Plata estuary (Argentina) and corresponds to a zone of interaction between a large sandy spit and a backwash tidal flat system. Methods combine statistics of wave climate time-series, analysis of wave energy using nearshore numerical modelling (SWAN) and comparison of pre- and post-storm morphological changes by means of shoreline change detection and satellite images derived indexes (CoastSat Toolkit and NDWI index respectively). Results allowed to characterize four types of major storms impacting the study area: High-Energy Storms (HES), defined by an average storm wave below the 1 % exceedance (>2.6 m), Long-Lived Storms (LLS) represented by an exceedance of the 1 % of Du (>60 h), Storm Groups (SG) in which storm return period is <6 days and Northeastern moderate storms (NMS) defined by their eastern, onshore oriented direction. Under HES and NMS storms erosional areas are dominant over depositional, causing shoreline retreat, a growth of the end-spit and the increase on sand deposition on the back-barrier areas. Under LLS and SG storms, the morphological impact varies alongshore, with multiple erosional hotspots found along the shoreline accompanied by a general flattens of the end-spit system.
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We report two cases with localized vascular malformations clinically resembling the "dominant lesion" seen in capillary malformation-arteriovenous malformation (CM-AVM) syndrome, however, lacking germline RASA1 variants but presenting double somatic RASA1 variants in affected tissue. Both patients presented with localized and superficial high-flow vascular malformations were treated with surgery and laser therapy and showed partial resolution. The study underscores the rarity of somatic RASA1 variants, contributes to understanding the "second-hit" pathophysiology in vascular lesions, and emphasizes the significance of clinical distinctions and genotyping for accurate diagnoses, offering implications for diagnosis, prognosis, and genetic counseling.
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Background: One of the most common causes of lung cancer relapse after clinical treatment is radioresistance. However, the mechanism underlying radioresistance remains unclear. In this study, we investigated the role of Ras p21 protein activator (RASA2) in non-small cell lung cancer (NSCLC). Methods: The messenger RNA (mRNA) of RASA2 was tested via reverse-transcription quantitative polymerase chain reaction (RT-qPCR) of cancer tissues from patients with NSCLC. Computed tomography (CT) and bioluminescent imaging (BLI) were used to monitor the tumor growth of patients and orthotopic mice, respectively. Protein-protein interaction was quantified via immunoprecipitation and glutathione S transferase (GST) pulldown assay. Western blotting was used to evaluate the phosphorylation and ubiquitination level of p53. Results: The results indicated a negative correlation between the mRNA expression levels of RASA2 in tumor tissues with patients' response to radiotherapy. Patients with a high expression of RASA2 had a lower objective response rate (ORR) after 1 month of radiotherapy than patients with low expression of RASA2 after 1 month of radiotherapy. In terms of mechanism, we proved that RASA2 can directly bind to p53 to promote the phosphorylation of p53, which inhibits its transcriptional activity and further promotes its degradation through the ubiquitin/proteasome pathway. In this process, the apoptosis of tumor cells is inhibited due to impaired p53 surveillance, which leads to radioresistance. Conclusions: Our results demonstrate that RASA2 negatively regulates p53 in cancer cells and therefore promotes radioresistance, providing a new predictive biomarker and a potential therapeutic target for radioresistance.
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Oncogenic mutations in KRAS typically impact the GAP-mediated and intrinsic GTP hydrolysis activity resulting in elevated levels of cellular KRAS-GTP. The development of biochemical assays for GTPase activity provides an opportunity to quantitatively measure the impact of these mutations on GTP hydrolysis. Here we describe a biochemical assay that measures the release of free phosphate upon hydrolysis of the GTP nucleotide and allows the measurement of intrinsic or GAP-stimulated GTP hydrolysis by KRAS. This assay can be used to measure GTPase activity under single turnover conditions.
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Proteínas Activadoras de GTPasa , Proteínas Proto-Oncogénicas p21(ras) , Proteínas Proto-Oncogénicas p21(ras)/genética , Hidrólisis , Mutación , Cinética , Guanosina Trifosfato , Proteínas Activadoras de GTPasa/metabolismoRESUMEN
The polycystic ovary syndrome (PCOS), a common endocrine disorder, is mainly related to infertility. Moreover, it is characterized by promoted androgen, suppressed ovulation and insulin resistance. Long non-coding RNA X inactive specific transcript (lncRNA XIST), known as an oncogene or a cancer inhabited factor, is involved in several disease. However, the diagnostic mechanisms of lncRNA XIST in PCOS have not been clarified. Our study aimed to explain whether lncRNA XIST regulates KGN cells proliferation and apoptosis via microRNA (miR)-212-3p/RASA1 axis in PCOS. Levels of lncRNA XIST, miR-212-3p and RASA1 in KGN cells were detected through reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay. Fluorescence in situ Hybridization (FISH) was performed to confirm the expression of lncRNA XIST and miR-212-3p in KGN cells. StarBase and dual-luciferase reporter assay were applied for exploring the interaction between miR-212-3p and RASA1. Cell viability, apoptosis, protein expression of Bcl-2 and Bax were assessed by MTT, flow cytometry analysis, RT-qPCR and western blot, respectively. We found that lncRNA XIST was low-expressed, miR-212-3p was over-expressed, and RASA1 was dramatically down-regulated in KGN cells. LncRNA XIST negatively regulated miR-212-3p expression in KGN cells. MiR-212-3p interacted with RASA1 and negatively regulated RASA1 levels in KGN cells. Up-regulation of lncRNA XIST signally decreased cells viability, stimulated more apoptotic cells, enhanced Bax expression, and depressed Bcl-2 level in KGN cells. However, these observations were abolished after miR-212-3p mimic treatment. Furthermore, miR-212-3p inhibitor significantly inhibited cell proliferation, enhanced more apoptotic cells, increased Bax expression, and decreased Bcl-2 level in KGN cells, and these effects were eliminated by RASA1-siRNA transfection. Our observations revealed that lncRNA XIST protects against PCOS through regulating miR-212-3p/RASA1 axis, suggesting that lncRNA XIST may be a promising therapeutic target for PCOS therapy.
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Breast cancer shows high mortality, especially in women worldwide. This report discusses a case of female patient with a history of Invasive Ductal Carcinoma (IDC) Rt Breast, ER, PR negative, Grade 3 (Gr3) Stage 3 (St3) seen in our OPD treated with supporting herbo-mineral-metallic combination of Ayurveda medicines. Generally, breast cancers of such subtype and that too in Lower Outer Quadrant (LOQ) are always of a concern and can be more troublesome to the patient. When the patient came for the first time, her chief complaint was palpable lump in her right breast for previous three months. We advised her to undergo relevant investigations and, it was found to be malignant. She underwent surgery, Modified Radical Mastectomy,(MRM), followed by chemotherapy. During chemotherapy, which was Adriamycin + Cyclophosphamide (AC) protocol 4 cycles, followed by Docetaxel 4 cycles, every 21 days. After 2 cycles, she started complaints of pain in both calf regions, numbness in fingers of hand and foot, severe generalized skin rash with itching, hyperacidity and constipation. She visited our clinic again for the same, and Ayurveda treatment was started to her at this point. So, at the time of commencement of treatment, the diagnosis was "IDC Rt Breast, LOQ, Gr3 St3, ER, PR negative HER2Neu positive, post op, on chemo". After appropriate analysis based on Ayurvedic and modern parameters, she was diagnosed to have vitiation of Rakta and Pitta (Dushti avastha), due to cyto-toxic nature of (Visha exposure) chemotherapy and medication was planned accordingly, along with chemotherapy protocol. The Ayurveda treatment showed significant relief in the chemotoxicity symptoms, within one month and she could tolerate further chemotherapy cycles very conveniently. On completion of chemotherapy, she was diagnosed to have need of good immunity (Vyadhi-Kshamatva). Based on this diagnosis, Ayurveda treatment protocol was changed and this new regimen continued for almost 6 years afterwards. Laboratory and imaging investigations performed periodically showed marked improvement, and even currently not showing any abnormality. Till date, there is no recurrence and patient is living completely normally for last 11 years. As all the symptoms and investigations showed near complete improvement; it may be concluded that probably add on Ayurveda treatment (Integrative approach) proved effective in this patient of IDC. We have observed 11 years of disease-free survival and excellent quality of life in this patient and still ongoing.
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OBJECTIVES: The aim of this in-vitro study was to investigate the influence of the measuring devices (mechanical and optical) on the surface values Ra/Sa and Rz/Sz of different materials and machined surfaces. MATERIAL AND METHODS: Mechanical (contact profilometry (CP): Perthometer S6P, Perthen Mahr, G) and optical (scanning electron microscope (SEM): Phenom, FEI, NL; confocal 3D laser scanning microscope (CLSM): VK-100, Keyence, J) measuring devices were used to determine the surface roughness Ra/Sa and Rz/Sz. Glass-ceramic (Empress, Ivoclar-Vivadent, FL), zirconia (Cercon HT, Dentsply, D), composite (Grandio, Voco, D), denture base material (Palapress, Kulzer, D) and titanium (grade 4) were investigated (n = 10 measurements) after surface finishing: sandblasting (Al2O3; 250 µm), diamond treatment (80 µm; wet), sandblasting (Al2O3; 50 µm), and polishing (grit of 4000; wet; Tegramin-25, Struers, D). STATISTICS: Shapiro-Wilk, ANOVA, Bonferroni post-hoc tests (α = 0.05). RESULTS: Surface characteristics Ra/Sa and Rz/Sz, which were detected with mechanical and optical measuring devices on different materials and surface finishing, showed significant (p ≤ 0.001, ANOVA) differences. Significant (p ≤ 0.045, Bonferroni) differences between CP, SEM and CLSM (line; area) were found, mainly for Ra/Sa. DISCUSSION: The surface roughness on different dental materials and differently machined surfaces were influenced by the individual mechanical and optical measuring devices. Optical methods measure a significantly higher roughness value for all materials and surface finishes.
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Diamante , Titanio , Microscopía Electrónica de Rastreo , Propiedades de Superficie , Microscopía Confocal , Ensayo de Materiales , Pulido DentalRESUMEN
OBJECTIVES: The invasive screening methods and the late stage diagnosis of colorectal carcinoma (CRC) are contributing for the devastative prognosis. The gradual shift of the disease pattern among younger generations requires the implementation of phytochemicals and traditional medicines. Arkeshwara rasa (AR) is a herb-mineral combination of Tamra bhasma/incinerated copper ashes and Dwigun Kajjali/mercury sulphide levigated with Calotropis procera leaf juice, Plumbago zeylanica root decoction and the decoction of three myrobalans (Terminalia chebula, Terminalia bellerica, Emblica Officinalis decoction)/Triphala decoction. METHODS: The SW-480 cell line was checked for the cytotoxicity and the cell viability criteria with MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. The acridine orange/ethidium bromide (AO/EtBr) assay revealed the depth of apoptosis affected cells in the fluorescent images. The FTIR analysis exhibited the graphical spectrum of functional groups within the compound AR. RESULTS: The IC50 from the 10-7 to 10-3 concentrations against SW-480 cells was 40.4⯵g/mL. The staining of AO/EtBr was performed to visualize live and dead cells and it is evident from the result that number of apoptotic cells increases at increasing concentration of AR. The single bond with stretch vibrations of O-H and N-H are more concentrated in the 2,500-3,200â¯cm-1 and 3,700-4,000â¯cm-1 of the spectra whereas, the finger print region carries the O-H and S=O type peaks. CONCLUSIONS: The AR shows strong cyto-toxicity against the SW-480 cells by inducing apoptosis. It also modulates cellular metabolism with the involvement of functional groups which antagonizes the strong acids. Moreover, these effects need to be analyzed further based in the in vivo and various in vitro models.
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Apoptosis , Minerales , Datos Preliminares , Línea Celular , Minerales/farmacologíaRESUMEN
BACKGROUND: The diverse specificity mode of cancer treatment targets and chemo resistance demands the necessity of drug entities which can address the devastating dynamicity of the disease. OBJECTIVES: To check the anti-tumour potential of traditional medicine rich in polyherbal components and metal nanoparticle namely Arkeshwara rasa (AR). MATERIAL METHODS: The AR was prepared in a modified version with reference from Rasaratna Samuchaya and characterized using sophisticated instrumental analysis including XRD, SEM-EDAX, TEM, TGA-DSC, and LC-MS and tested against the MDA-MB-231 cell line to screen cell viability and the cytotoxicity with MTT, SRB and the AO assay. RESULTS: XRD pattern shows cubic tetrahedrite structure with Sb, Cu, S peaks and trace elements like Fe, Mg, etc. The particle size of AR ranges between 20 and 30 nm. The TGA points thermal decomposition at 210 °C and the metal sulphide peaks in DSC. LC-MS analysis reveals the components of the formulation more on the flavonoid portion. The IC50 value of MTT and SRB are 25.28 µg/mL and 31.7 µg/mL respectively. The AO colorimeter substantiated the cell viability and the apoptosis figures of the same cell line. The AR exhibits cytotoxicity and reaffirms the apoptosis fraction with SRB assay. CONCLUSIONS: The Hesperidine, Neohesperidin, Rutin components in the phytochemical pool can synergize the anti-tumour potential with either influencing cellular pathways or decreasing chemo resistance to conventional treatment. AR need to be further experimented with reverse transcription, flow cytometry, western blotting, etc.
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Gairika (red ochre) has a long history of influencing human civilization. Gairika is a rich source of nutrients used for reproductive and brain health. Gairika is mentioned as an antacid drug in Indian Ayurvedic medicine under Laghu Sutashekhara Rasa (LSR). However, a detailed study on LSR has not been reported to date. In the present study, LSR was prepared, and a pharmaceutical SOP (standardization procedure) was reported to obtain batch-to-batch reproducibility. LSR was characterized using FTIR, XRD, SEM-EDX, and TGA analyses. LSR was tested in vitro for its antacid activity. Advanced instrumentation revealed that LSR formation produced symmetrical particles (5-8 µm) with kaolin, kaolinite, quartz, goethite, and hematite, along with the phytoconstituents of Goghrita (clarified cow's butter), Shunthi, and Nagawalli, as confirmed by GC-MS/MS analysis. The FTIR study revealed the formation of a chelating complex of goethite and hematite along with their phytoconstituents. XRD analysis confirmed the presence of kaolin, kaolinite, quartz, goethite, and hematite. Using in vitro antacid experiments, LSR and Shunthi demonstrated significant antacid activity as compared to antacid drugs and standards in the market, such as CaCO3. The DPPH assay revealed IC50 values of 12.16 ± 1.23 mg/mL, which is 0.0029 of Trolox-equivalent antioxidant activity. The inhibition (18 ± 4 mm) against pathogens (S. aureus, E. coli, P. aeruginosa, and B. subtilis) and the prominent growth of gut microbiota-supported strains (S. boulardii, L. paracasei, and L. plantarum) observed on LSR formulation were indicative of LSR application as a prebiotic. Here, the mechanism of purification and levigation mentioned in the classical literature of LSR was established. Overall, purification of Gairika with cow ghee and levigation with Nagawalli may enhance the solubility, bioavailability, and shelf-life of LSR through hydration and co-crystallization mechanisms. This is the first comprehensive report on the pharmaceutical validation of LSR and its characterization. The results of the present study could contribute to the development and reliable reproduction of LSR and the utility of environmental red ochre as a medicine in combination with Shunthi (Zingiber officinale Roxb.), as prescribed under Indian Ayurvedic medicine.
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Introducción. Los síndromes de sobrecrecimiento corporal segmentario son un grupo de enfermedades poco frecuentes caracterizadas por exceso de crecimiento en una o más partes del cuerpo relacionadas, en su mayoría, con mutaciones en mosaico en la vía de señalización AKT/PI3K/mTOR y RAS-MAPK. Nuestro objetivo fue analizar las características clínicas y auxológicas, y la calidad de vida relacionada a salud (CVRS) en este grupo de pacientes en un hospital de tercer nivel de atención. Población y métodos. Estudio transversal de una cohorte en seguimiento. Se analizaron edad, sexo, datos sociodemográficos, mediciones antropométricas del segmento afectado y del contralateral, complicaciones, tratamiento, calidad de vida (PedsQL4.0) y dolor. Se calcularon medidas centrales y de dispersión. Se realizó análisis univariado entre calidad de vida y variables incluidas. Resultados. Se incluyeron 50 pacientes, 29 varones. Mediana de edad 9,95 (r 1,44-17,81) años. El diagnóstico más frecuente fue síndrome de sobrecrecimiento relacionado a PIK3CA (PROS) (37/50). Mediana de número de segmentos afectados 2 (r: 1-7) por niño. Cuarenta casos presentaron malformación vascular; 20, capilar. El dolor (24/50) fue la complicación más frecuente. Treinta y un pacientes mostraron asimetría de longitud de miembros inferiores, < 5 cm. La estatura se ubicó entre los centilos 50 y 97 en la mayoría de los niños. Menor CVRS se observó en mujeres, en pacientes con malformación vascular compleja y necesidades básicas insatisfechas (NBI). Conclusiones. PROS fue el diagnóstico más frecuente. El dolor fue una complicación frecuente. La CVRS fue menor en mujeres, pacientes con malformación vascular combinada y NBI.
Introduction. Segmental overgrowth syndromes are a group of rare diseases characterized by overgrowth in one or more parts of the body, mostly related to mosaic mutations in the AKT/PI3K/mTOR and RASMAPK signaling pathway. Our objective was to analyze the clinical and auxological characteristics and health-related quality of life (HRQoL) in this group of patients at a tertiary care hospital. Population and methods. Cross-sectional study of a follow-up cohort. Age, sex, sociodemographic data, anthropometric measurements of the affected and contralateral segments, complications, treatment, quality of life (PedsQL 4.0), and pain were analyzed. Central and dispersion measures were estimated. A univariate analysis between the quality of life and study variables was done. Results. A total of 50 patients were included; 29 were males. Median age: 9.95 (r: 1.4417.81) years. The most common diagnosis was PIK3CA-related overgrowth spectrum (PROS) (37/50). The median number of affected segments was 2 (r: 17) per patient. Vascular malformations were observed in 40, and capillary malformations, in 20 patients. Pain was the most common complication (24/50). An asymmetry of the lower extremities of < 5 cm was observed in 31 patients. In most children, height was between the 50th and 97th percentiles. A lower HRQoL was observed among girls, patients with complex vascular malformations, and those with unmet basic needs (UBNs). Conclusions. PROS was the most common diagnosis. Pain was the most common complication. HRQoL was lower among girls, patients with combined vascular malformations, and those with UBNs.
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Humanos , Preescolar , Niño , Adolescente , Calidad de Vida , Malformaciones Vasculares , Dolor , Síndrome , Transducción de Señal , Estudios Transversales , MutaciónRESUMEN
PURPOSE: The Government of India offers various schemes for various classes of citizens. Most of the application forms of schemes to be filled are in English and it is observed that monolingual individuals find it difficult to access and fill the forms. This paper addresses the challenges faced by monolingual individuals in India, particularly the elderly, people with impairments, and those from marginalized communities. The proposed work is to create an interactive system called "Dhvani" voicebot, specifically designed for the Kannada language. It helps users in identifying suitable government schemes and fills forms in English. MATERIALS AND METHODS: The proposed system is developed using the RASA chatbot framework and NLP techniques to comprehend user utterances. RNN and SVM algorithms are employed to ensure smooth conversation flow and interaction with the users. To enhance scheme suggestion accuracy, a knowledge graph is created, containing relevant data on government schemes. RESULTS: The intent classification model achieves an accuracy of 97%, indicating its ability to accurately understand user intentions. The integration of a knowledge graph improves the accuracy of scheme identification and suggestion to users. The system automates the process of filling out government scheme forms based on user inputs. CONCLUSION: Dhvani voicebot system presents a practical solution to address the challenges faced by monolingual individuals in accessing government schemes in India. The high accuracy of intent classification and the use of a knowledge graph contribute to the system's effectiveness. The study suggests that this system can be extended to other languages.
An automated tool called "Dhvani" will solve the problem of aged, illiterate and physically challenged persons filling forms in post offices and banks. Most of the schemes, pension funds, cash withdrawal, cash deposit is through these organizations. So. the tool makes the process easier for the above mention persons without the help of others.An intent recognition and interactive tool developed in Kannada Language which is widely spoken in Karnataka, India. The digital resources available in Kannada Language is very sparce.Use of technology like interactive tool, Knowledge graph, RNN and SVM are used in the development of the tool.Government scheme recommendation interactively makes the users to choose the scheme faster in an interactive way.The form is filled automatically and can be edited to rectify mistakes.
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ARHGAP35, which encodes p190A RhoGAP (p190A), is a major cancer gene. p190A is a tumor suppressor that activates the Hippo pathway. p190A was originally cloned via direct binding to p120 RasGAP (RasGAP). Here, we determine that interaction of p190A with the tight-junction-associated protein ZO-2 is dependent on RasGAP. We establish that both RasGAP and ZO-2 are necessary for p190A to activate large tumor-suppressor (LATS) kinases, elicit mesenchymal-to-epithelial transition, promote contact inhibition of cell proliferation, and suppress tumorigenesis. Moreover, RasGAP and ZO-2 are required for transcriptional modulation by p190A. Finally, we demonstrate that low ARHGAP35 expression is associated with shorter survival in patients with high, but not low, transcript levels of TJP2 encoding ZO-2. Hence, we define a tumor-suppressor interactome of p190A that includes ZO-2, an established constituent of the Hippo pathway, and RasGAP, which, despite strong association with Ras signaling, is essential for p190A to activate LATS kinases.