Dreadful Disease Research Articles

Advanced biomaterials for regenerative medicine and their possible therapeutic significance in treating COVID-19: a critical overview.

The potential of biomaterials in medical sciences has attracted much interest, especially in promoting tissue regeneration and controlling immune responses. As COVID-19 pandemic broke out, there was an increased interest in understanding more about how biomaterials could be employed to fight this dreaded disease, especially in the context of regenerative medicine. Out of the numerous regenerative medicine possibilities, stem cells and scaffolding (grafting) technology are two major areas in modern medicines and surgery. Mesenchymal stem cells are useful in tissue repair, tailored therapy and treating COVID-19. Using biomaterials in COVID-19 treatment is intricate that needs multi- and cross-disciplinary research. Cell-based therapy and organ transplant pose immunological rejection challenge. Immunomodulation enhanced, tumorigenicity decreased, inflammation addressed and tissue damage restricted bioengineered stem cells need clinical insights and validation. Advanced stem cell based therapies should ideally be effective, safe and scalable. Cost and scalability shall dictate the dawn of technoeconomically feasible regenerative medicine. A globally standard and uniform approval process could accelerate translational regenerative medicine. Researchers, patient advocacy organisations, the regulators and the biopharmaceutical stakeholders need to join hands for easy navigation of regulatory measures and expeditious market entry of regenerative medicine. This article summarises advances in biomaterials for regenerative medicine, and their possible therapeutic benefits in managing infectious diseases like COVID-19. It highlights the significant recent developments in biomaterial design, scaffold construction, and stem cell-based therapies to treat tissue damage and COVID-19 linked immunological disregulation. It also highlights the potential contribution of biomaterials towards creating novel treatment strategies to manage COVID-19.

Knowledge And Attitude Regarding Rabies Prevention Among Adults Residing Under The Field Areas Of Medical College Health Unit, Pangappara

ABSTRACT Rabies has been one among the most dreaded diseases to man since antiquity. The present study was intended to assess the knowledge and attitude regarding rabies prevention among adults residing under the field areas of Medical College Health Unit, Pangappara. The objectives of the study were to assess the knowledge and attitude regarding rabies prevention, to assess the practice regarding rabies prevention, to find out the correlation between knowledge and attitude and to find out the association between knowledge of adults regarding rabies prevention with sociodemographic variables. The research approach adopted for the study was quantitative and the data was collected from 408 participants. The study design was cross sectional design and participants were selected using cluster sampling technique. Socio demographic data and the knowledge were assessed using an interview schedule, attitude and practice were assessed using a five point Likert scale and a checklist respectively. Data analysis was carried out using both descriptive and inferential statistics. The results showed that 47.1% had good knowledge,28.4% had average knowledge and 24.5% had poor knowledge regarding rabies prevention and 38% of adults had positive attitude,36% had uncertain attitude and 26% had negative attitude towards rabies prevention,45.9% reported good practice after an animal bite. The study revealed that there was a moderate positive correlation between knowledge and attitude (r = 0.443 and p < 0.05) and there was a significant association between knowledge of adults regarding rabies prevention with age, socio economic status and adults participation status in rabies prevention campaign. The study concludes the necessity for preventing the mortality by dog mediated Rabies.

Utilizing Multi-layer Perceptron for Esophageal Cancer Classification Through Machine Learning Methods

Aims This research paper aims to check the effectiveness of a variety of machine learning models in classifying esophageal cancer through MRI scans. The current study encompasses Convolutional Neural Network (CNN), K-Nearest Neighbor (KNN), Recurrent Neural Network (RNN), and Visual Geometry Group 16 (VGG16), among others which are elaborated in this paper. This paper aims to identify the most accurate model to facilitate increased, improved diagnostic accuracy to revolutionize early detection methods for this dreadful disease. The ultimate goal is, therefore, to improve the clinical practice performance and its results with advanced machine learning techniques in medical diagnosis. Background Esophageal cancer poses a critical problem for medical oncologists since its pathology is quite complex, and the death rate is exceptionally high. Proper early detection is essential for effective treatment and improved survival. The results are positive, but the conventional diagnostic methods are not sensitive and have low specificity. Recent progress in machine learning methods brings a new possibility to high sensitivity and specificity in the diagnosis. This paper explores the potentiality of different machine-learning models in classifying esophageal cancer through MRI scans to complement the constraints of the traditional diagnostics approach. Objective This study is aimed at verifying whether CNN, KNN, RNN, and VGG16, amongst other advanced machine learning models, are effective in correctly classifying esophageal cancer from MRI scans. This review aims at establishing the diagnostic accuracy of all these models, with the best among all. It plays a role in developing early detection mechanisms that increase patient outcome confidence in the clinical setting. Methods This study applies the approach of comparative analysis by using four unique machine learning models to classify esophageal cancer from MRI scans. This was made possible through the intensive training and validation of the model using a standardized set of MRI data. The model’s effectiveness was assessed using performance evaluation metrics, which included accuracy, precision, recall, and F1 score. Results In classifying esophageal cancers from MRI scans, the current study found VGG16 to be an adequate model, with a high accuracy of 96.66%. CNN took the second position, with an accuracy of 94.5%, showing efficient results for spatial pattern recognition. The model of KNN and RNN also showed commendable performance, with accuracies of 91.44% and 88.97%, respectively, portraying their strengths in proximity-based learning and handling sequential data. These findings underline the potential to add significant value to the processes of esophageal cancer diagnosis using machine learning models. Conclusion The study concluded that machine learning techniques, mainly VGG16 and CNN, had a high potential for escalated diagnostic precision in classifying esophageal cancer from MRI imaging. VGG16 showed great accuracy, while CNN displayed advanced spatial detection, followed by KNN and RNN. Thus, the results set new opportunities for introducing advanced computational models to the clinics, which might transform strategies for early detection to improve patient-centered outcomes in oncology.

From the Gorgon's blood to Behring's Blutserumtherapie: A long path towards serum therapy.

At the end of the 19th century medicine was turned upside down by the development of serum therapy, a great therapeutic revolution as was vaccination a few years earlier. Many serums were developed, the most famous being the German doctor Emil von Behring's diphtheria serum, which saved countless children's lives from this dreadful disease. The discovery of the serum therapy principle, allowed by the progressive understanding of humoral immunity, occurred both in Germany and France, almost at the same time. Interestingly, this principle arose from two different intellectual paths, reviving the age-old opposition between mechanism and vitalism: while Behring came to this discovery reasoning as a chemist, French researchers Charles Richet and Jules Héricourt behaved as physiologists, focusing on the role of the host in the host-pathogen interaction. However, we should maybe consider that serum therapy history begins much earlier. Great forerunners must not be forgotten, especially researchers who investigated the field of immunity as soon as in the very beginning of the microbiological revolution; but also many people throughout centuries who tried to cure diseases with blood: as a transfer of blood serum, serum therapy also lies in the tradition of blood transfusion.

Integrating Ayurvedic philosophy with modern technologies for drug research and development: A critical need of mechanistic insights for wider acceptability

Ayurveda is a holistic science emphasizing healing and maintaining harmony and balance in the body. Medicines from natural resources and in pre-defined dosage forms are integral parts of successful Ayurvedic treatment in various diseases including complex ailments, such as cancer. Ayurvedic medicines are cocktails of several active phyto-compounds and/or natural resources and no isolated/purified molecules are used in the treatment. However, various unique methods employed using natural media, such as water, lipids, buttermilk, and lemon juice, just to name a few, lead to the elimination of unwanted constituents/impurities and enhance the bioavailability and efficacy of the drug. Such plausible alterations, selection, and/or retention of signature phytocompounds in the raw materials, during the process, and in the final drug need to be studied for precise product identification and analysis. Critical standardization of the manufacturing procedures is, therefore, mandatory for quality fidelity, assurance, and optimum efficacy. Moreover, the simultaneous multi-level and/or multi-targeted actions of Ayurvedic medicines against various dysfunctions due to their complex nature makes it extremely challenging to understand the mechanistic aspects during pre-clinical and clinical studies.The present article focuses on probable challenges and ideal roadmaps for standardization and characterization of such herbal as well as metallic-mineral Ayurvedic medicines being used for various simple and complex diseases like cancer and their treatments. It is emphasized that Ayurvedic manufacturing procedures should be followed meticulously and the finished product be characterized thoroughly using advanced pharmaceutical and analytical techniques. It is also accentuated that detailed monographs or dossiers including shelf-life studies need to be officially published for knowledge dissemination and worldwide acceptance. Finally, safety and efficacy studies as per modern pharmacology ought to be conducted in suitable animal models for the judicious use of these medicines. Mainstream or adjuvant treatment of dreadful diseases such as cancer with Ayurvedic medicines will only be fruitful through rational experimentation and ethical reporting.

Bioassay-guided isolation of dehydrocostus lactone from Echinops kebericho as a leishmanicidal drug

Several strains of Leishmania parasite are involved in the occurrence of leishmaniasis infections, which makes its prevention and treatment very challenging. Currently, all forms of leishmaniasis are being treated with chemical drugs, which have limitations and adverse effects. Discovering antileishmanial agents from natural sources can lead to novel drugs against this dreadful disease. The essential oils and nonpolar solvent extracts of the roots of E. kebericho exhibit antileishmanial activity. Thus, the isolation of the leishmanicidal compounds from the roots of E. kebericho through a bioassay-guided technique was carried out in this study. The present finding showed that the essential oil and hexane fraction of crude extract from the roots of E. kebericho possessed significant leishmanicidal activity against L. major and L. tropica. Dehydrocostus lactone (1), one of the major constituents of the essential oil and hexane fraction, was more active than the standard drug miltefosine against L. major and L. tropica promastigotes. The presence of α-methylene, γ-lactone is the responsible moiety of dehydrocostus lactone towards the leishmanicidal activity against the tested Leishmania species. The MTT assay of dehydrocostus lactone showed inactive toxicity against the human cervical carcinoma HeLa cells. In addition, dehydrocostus lactone exhibits a broad spectrum of antibiotic activities. Based on this interesting finding, dehydrocostus lactone was identified as a potential lead for treating infections caused by Leishmania.

Synthesis, spectral elucidation and DNA binding studies of cadmium(II) carboxylates with nitrogen donor heteroligands

A new series of novel homoleptic and heteroleptic Cd(II) complexes using cyclopropanecarboxylic acid (HL1) and cyclopentanecarboxylic acid (HL2) as main ligands and N-donor species like 2,2′-bipyridine (bpy), 1,10-phenanthroline (phen), and 2,9-dimethyl-1,10-phenanthroline (Me2phen) as co-ligands were prepared and characterized by FT-IR, multinuclear (1H and 13C) NMR, and UV–Visible spectroscopies. Furthermore, the crystal structure of the Cd(II) complex coordinated by cyclopentanecarboxylic acid (HL2) and 1,10-phenanthroline (phen) was explored by single crystal X-ray diffraction (SC-XRD) analysis. The crystal structure was binuclear, in which the coordination geometry around each cadmium center was distorted pentagonal bipyramidal coordination geometry. Various intermolecular interactions were accountable for stabilizing the supramolecular associations, which were seen by Hirshfeld surface analysis in terms of interatomic contacts. The spectroanalytical data of the synthesized complexes confirm the absence of the –OH band in the spectra of complexes as compared to the spectra of the free ligands, which favour the formation of complexes. The nature of complex-DNA interaction and the effect of the coordination of heteroligands on the binding strength of complexes were probed through UV–Visible spectroscopy and cyclic voltammetry. The obtained data confirm that the interaction of DNA with the complexes is dual: intercalation as well as groove binding. The DNA binding constants (Kb) and Gibb’s free energy changes (ΔG) were also determined for these complexes. This study aims to project effective drugs with the least harmful effects that could be useful for mankind against dreadful diseases.

Probable paralytic rabies in a dog: ante-mortem clinical diagnosis implications in limited resource settings.

Rabies is a dreadful zoonotic viral disease that affects animals and humans with a fatality rate of 100%. This report aims to create awareness among the veterinarians and general public about the paralytic form of rabies in order to understand the antemortem clinical diagnosis implications in limited resource settings, so as to follow the post-exposure prophylaxis at the golden hour period of rabies transmission. A one-year-old female dog was presented to the Ambulatory Clinic Unit, Veterinary Clinical Complex, Veterinary College and Research Institute, Theni, Tamil Nadu, India with the ailment of a dropped jaw and was unable to swallow food and water for the past three days. Epidemiological investigations revealed that the animal had dog-bitten wounds from a week ago. On clinical examination, facial distortion, changes in the vocal cord, and paralysis of the throat muscle were noticed. Based on the anamnesis, clinical, and epidemiological investigations, the animal was diagnosed to be a probable case of paralytic form of canine rabies. In the limited resource settings, antemortem clinical diagnosis was practiced to suspect rabies-infected dogs. Further, the owner was advised to implement preventive measures to safeguard against rabies infection. The dog was kept under isolation and succumbed on day two with evidence of progressive paralytic signs. This report emphasizes the importance of paralytic rabies, alongside of furious form of rabies, further creating awareness among the general public about the antemortem clinical diagnosis under limited resource settings.

Mining parasites for their potential as novel therapeutic agents against cancer.

Despite recent advances in the management and therapeutic of cancer, the treatment of the disease is limited by its high cost and severe side effects. In this scenario, there is an unmet need to identify novel treatment alternatives for this dreaded disease. Recently there is growing evidence that parasites may cause anticancer effects because of a negative correlation between parasitic infections and tumour growth despite some parasites that are known to exhibit pro-carcinogenic effects. It has been observed that parasites exert an anticancer effect either by activating the host's immune response or by secreting certain molecules that exhibit anticancer potential. The activation of the immune response by these parasitic organisms results in the inhibition of some of the hallmarks of cancer such as tumour proliferation, angiogenesis, and metastasis. This review summarizes the current advances as well as the mechanisms underlying the possible implications of this diverse group of organisms as anticancer agents.

Combinatorial strategies targeting NEAT1 and AURKA as new potential therapeutic options for multiple myeloma.

Multiple myeloma (MM) is a dreadful disease, marked by the uncontrolled proliferation of clonal plasma cells (PCs) within the bone marrow (BM). MM is characterized by a highly heterogeneous clinical and molecular background, supported by severe genomic alterations. Important deregulation of long non-coding RNAs (lncRNAs) expression has been reported in MM patients, influencing progression and therapy resistance. NEAT1 is a lncRNA essential for nuclear paraspeckles and involved in gene expression regulation. We showed that NEAT1 supports MM proliferation making this lncRNA an attractive therapeutic candidate. Here, we used a combinatorial strategy integrating transcriptomic and computational approaches with functional high-throughput drug screening, to identify compounds that synergize with NEAT1 inhibition in restraining MM cells growth. AUKA inhibitors were identified as top-scoring drugs in these analyses. We showed that the combination of NEAT1 silencing and AURKA inhibitors in MM profoundly impairs microtubule organization and mitotic spindle assembly, finally leading to cell death. Analysis of the large publicly CoMMpass dataset showed that in MM patients AURKA expression is strongly associated with reduced progression-free (p < 0.0001) and overall survival probability (p < 0.0001) and patients displaying high expression levels of both NEAT1 and AURKA have a worse clinical outcome. Finally, using RNA-sequencing data from NEAT1 knockdown (KD) MM cells, we identified the AURKA allosteric regulator TPX2 as a new NEAT1 target in MM and as a mediator of the interplay between AURKA and NEAT1, therefore providing a possible explanation of the synergistic activity observed upon their combinatorial inhibition.

Contribution of Srisailam in the Historical Progress of Ayurveda During Medieval Period

Ayurveda, an ancient medical science on earth which was already a highly developed science with its manifold specialized practice in pre Buddhist era. It was gradually declined in the medieval period due to many political reasons. Rasa sastra, a branch related to Ayurveda which deals with herbomineral medicines developed during medieval period. Srisailam is considered to be centre for many Buddhists, Tantrics and Siddhas. Because of the efforts of Siddha yogis like Acharya Siddha Nagarjuna, Ayurveda again flourished with new branches (Rasa sasthra) &amp; new drugs (Rasoushadhis). These medicines are prepared by Parada i.e., mercury and other metals as main ingredients along with some other herbal drugs available in the Nallamala and river banks of Krishna near Srisailam. At present also different varieties of medicinal plants, metals and minerals abundantly available at Srisailam and surrounding areas which are very much useful in treating many chronic as well as dreadful diseases.

Role of Pathya-Apathya in Pranavaha Srotas

In Ayurveda food is considered as superior medicine and one among the vital supporting pillars of health [1]. A diet should provide physical and mental well-being, along with the dynamic equilibrium of various structural and functional units of the individual. Pranavaha srotas includes diseases of respiratory system ie, swasa, kasa, hikka, rajayakshma where aetiology prevention is the primary treatment. Difficulty in breathing or shortness of breath caused due to excessive intake of kapha aggravating food and regimen the kapha along with vata gets into pitta sthana which is termed as swasa (Asthma). Vitiated vata dosha along with kapha dosha obstructs the pranavaha, udakavaha and annavaha srotasa (respiratory system, watery elements &amp; digestive system) and produces different types of hikka vyadhi. Hikka canbe correlated in modern science with hiccup. The vitiated Prana vayu along with udana vayu which further gets aggravated in association with other doshas and expelled out forcefully with a coughing sound like the broken bronze vessel, called as Kasa. Rajayakshma is one among the Asta mahagadas (eight dreadful diseases) described by Acharya Charaka and is known as the "king of the disease", it can be correlated to pulmonary tuberculosis due to similarity in symptoms. Globally, respiratory diseases both communicable and noncommunicable, are among the leading causes of mortality, morbidity, economic and societal burden, and disability-adjusted life years. Respiratory diseases are abnormalities that affect the air passages, the bronchi, and the lungs. By understanding the parameters of pathya/wholesome and apathy/unwholesome relating to respiratory system one can easily prevent, cure and avoid recurrence of the disease pertaining to the same. Pathya can be understood as those practices which do not afflict the patha/srotas/channels of circulation and is relishing to manas (mind). On the contrary, Apathya is that which is Apriya (Not relished) to Manas, such a Dravya should not be consumed on daily basis.

Level of Awareness on Tuberculosis, Roles and Functions Treatment Partner and Implementation of the Treatment Partner Strategy

This study determined the level of awareness on tuberculosis, roles and functions of treatment partners and Implementation of the treatment partner strategy. It also looked into the significant relationship between the profile of the respondents, the level of awareness on tuberculosis of the respondents, the level of roles and functions of the respondents, the level of implementation of the treatment partner strategy and its significant relationship. This study utilized the descriptive-correlational design utilizing quantitative approach in determining the profile, level of awareness on tuberculosis and level of roles and functions of treatment partners. Furthermore, it will also be used to determine the significant variables correlated. Based on the findings of the study, the following conclusions were drawn: There is no significant relationship between profile variables and level of awareness on tuberculosis and level of roles and functions of the treatment partners. But there is a significant relationship between awareness and roles and functions as well as roles and functions of treatment partners and implementation of the treatment partners program. Based on the results of the study, the following are recommended: The TB patients should be aware of the personal, social and economic consequences of the dreaded disease and that they will live normal lives after TB treatment with the help of their TB treatment partners. Treatment Partners should realize their role in treating TB in their locality and their overall contribution in helping increase cure rate on TB. Moreover, the family members and significant others should understand the importance of having a TB treatment partner. Furthermore, rural health workers should help the frontline workers to really insist on having their community volunteer health workers as the first priority to be the TB patient's treatment partners. And lastly, the Ministry of Health should continuously provide technical assistance to the community volunteer health workers in the form of training packages and other non-monetary benefits such as those provided in the law.

Evaluation of non-systemic fungicides for growth inhibition of Alternaria burnsii causing blight in cumin

Cumin (Cuminum cyminum L.) is an important seed spice crop at world level and India is the leading producer (70% of world production), consumer and exporter of cumin in the world. Almost 80% of the crop cultivated is consumed in India. The crop yield is affected by several biotic and abiotic factors, among them, blight caused by Alternaria burnsii (Uppal, Patel and Kamat) is one of the most dreaded diseases and a major production constrain for the successful cultivation of cumin crop. Among the non-systemic fungicides tested, captan 75% WP, chlorothalonil 75 % WP and mancozeb 75 % WP were most effective with 95.67, 95.62 and 94.86 per cent growth inhibition, respectively whereas hexaconazole 5 % EC was most effective in systemic fungicides with 99.98 per cent inhibition followed by Tebuconazole 25.9 % EC 87.40 per cent inhibition.

AN AYURVEDIC MANAGEMENT OF KITIBHA KUSHTHA: A CASE STUDY

The word "Kushtha" refers to a disease that despises skin. Kitibha kushtha is a type of kshudra kushtha that predominates over Vata Kapha dosha. Psoriasis is a chronic and dreadful disease that can have substantial psychological and social impacts on a patient’s life. Psoriasis is a non-contagious, chronic, inflammatory and proliferative skin disorder characterised by red, thickened plaques with silvery scales. Objectives: This study evaluated the efficacy of Antaparimarjan and Bahiparimarjan chikitsa in Kitibha Kushtha. Materials and Methods: Here, we report a case of a male patient of middle age presented with Shyava varnata, Parushata, and Kanduta for 30 years to OPD. The disease manifests psychosomatically. Based on symptoms and clinical findings, the case was diagnosed as kitibha kushta. This case was treated effectively through therapeutic interventions in Ayurveda, i.e., Antaparimarjan (internal administration of drugs) and Bahiparimarjan Chikitsa (local application). The patient reported significant improvement in signs and symptoms

Evaluation and Comparison of Different Surgico-chemotherapeutic Regimens for the Treatment of Malignant Canine Mammary Tumours

Background: Cancer has been regarded as the most dreaded disease for both human and animals because of its incurability. Canine mammary tumours are common and major problem encountered by academicians and practicing veterinarians. As a result, the current study was conducted to examine the effectiveness and overall impact of different surgico-chemotherapeutic approaches in treating malignant mammary tumors in dogs. Methods: The investigation involved 18 clinical instances of mammary tumors in different breeds, regardless of age or sex and were divided into three groups of six animals each. In Group S, only surgical excision of tumour was performed while animals of Group SD and Group SV were treated with surgical excision followed by administration of Doxorubicin (30 mg/m2) BSA and Vincristine sulphate (0.025 mg/kg) intravenously alongwith DNS at 7th and 14th post-operative days respectively. Different physiological and haemato-bichemical parameters i.e. Hb, PCV, TLC, TPC, DLC, Serum glucose, TSP, SUN, SC, ALT, AST and ALP were recorded preoperatively, postoperatively and following chemotherapy at 10th, 30th and 60th day intervals. Result: The present study showed transient change in the physiological, haematological and biochemical profiles following surgery and chemotherapy treatment. The histopathological analysis showed more cases of adenocarinoma which were followed by mixed carcinoma. Surgery combined with chemotherapy (doxorubicin and vincristine) resulted in minimal to no reoccurrence with few adverse reactions including inappetance, vomition, anaemia and alopecia. It was concluded that the most effective treatment for malignant mammary tumors in dogs is surgical excision followed by sequential vincristine therapy, which efficiently regresses the tumor without causing relapse.

Cow Based Inputs for Sustainable Agriculture: A Review

Food safety is of prime importance at present because the consumption of food products with chemical residues above the threshold levels is causing dreadful diseases in living beings and deteriorating soil health too. The current global scenario firmly emphasizes the need to adopt agricultural practices that are ecologically safe for sustainable food production. Hence, it is necessary to adopt organic farming which improves the health of Agro-ecosystems besides providing safe food and conserving the soil fertility and soil biota. There is a need to identify a suitable substitute in place of chemical fertilizers which are economically cheaper and ecofriendly. In this context, Cow-based inputs (dung, urine, ghee, milk) play an important role in organic farming as an alternative to chemical fertilizers which help in the growth of the crop and provide eco-safety food

Therapeutic Potential of Minerals Preparations wsr to Raktapitta (Bleeding Disorders)

Raktapitta is described in the fourth Adhyaya of the Agniveshtantra. The disease has been described after Jwara chikitsa. Acharya Charaka has described Raktapitta as Mahagada and an acute dreadful disease, having more severity and quick acting like fire. As the name suggests- Raktapitta is caused by the vitiation of two body elements i.e., Rakta and Pitta. The main etiology of the disease is said to be the Pitta vardhak ahara, which leads to the vitiation of the Pitta dosha. Since, Rakta dhatu is said to be Samandharma as that of Pitta dosh, vitiation of Pitta leads to the aggravation of Rakta dhatu. This Dhatu, a concept from Ayurveda, is often increased due to its Swapramana. This increase can cause it to move through the external apertures of the body, leading to potentially lethal diseases that require immediate attention. The treatment protocol for such conditions is not a one-size-fits-all. It is primarily based on the affected site, along with other general considerations like Dosha and Bala. This personalized approach is what makes Ayurveda stand out in the realm of holistic health. Treatment often includes nourishment therapy (Brimhana) or attenuation therapy (Langhana). Brimhana therapy focuses on strengthening the body, while Langhana therapy aims to reduce excesses. Langhana therapy can further be divided into purification therapy (Sodhana) and curative therapy (Samana), each with its unique benefits. The article deals with understanding the etiology, symptoms and treatment of the disease and the role of minerals in its management.

Oschib1 gene encoding a GH18 chitinase confers resistance against sheath blight disease of rice caused by Rhizoctonia solani AG1-IA.

Sheath blight disease of rice caused by Rhizoctonia solani AG1-IA, is a major fungal disease responsible for huge loss to grain yield and quality. The major limitation of achieving persistent and reliable resistance against R. solani is the governance of disease resistance trait by many genes. Therefore, functional characterization of new genes involved in sheath blight resistance is necessary to understand the mechanism of resistance as well as evolving effective strategies to manage the disease through host-plant resistance. In this study, we performed RNA sequencing of six diverse rice genotypes (TN1, BPT5204, Vandana, N22, Tetep, and Pankaj) from sheath and leaf tissue of control and fungal infected samples. The approach for identification of candidate resistant genes led to identification of 352 differentially expressed genes commonly present in all the six genotypes. 23 genes were analyzed for RT-qPCR expression which helped identification of Oschib1 showing differences in expression level in a time-course manner between susceptible and resistant genotypes. The Oschib1 encoding classIII chitinase was cloned from resistant variety Tetep and over-expressed in susceptible variety Taipei 309. The over-expression lines showed resistance against R. solani, as analyzed by detached leaf and whole plant assays. Interestingly, the resistance response was correlated with the level of transgene expression suggesting that the enzyme functions in a dose dependent manner. We report here the classIIIb chitinase from chromosome10 of rice showing anti-R. solani activity to combat the dreaded sheath blight disease.

Abstract LT05: METTL8-MEDIATED EPITRANSCRIPTOMIC REGULATION OF GBM CYCLING STATE IS DEPENDENT ON RTK/PI3K/AKT SIGNALING

Abstract Glioblastoma (GBM) is a lethal brain tumor with limited treatment options. Treatment failures are often attributed to the existence of glioma stem cells (GSCs), which confer intratumoral heterogeneity and therapy resistance. Contrary to common belief that cancer cells employ aerobic glycolysis (Warburg effect) to sustain their metabolic requirements, GSCs rely on oxidative phosphorylation (OXPHOS) for energy production. As a result, GSCs are uniquely sensitive to OXPHOS inhibitors (Gboxin), as well as mitochondrial translation inhibitors which disrupt OXPHOS. METTL8 is a newly discovered mitochondrial methyltransferase which catalyzes m3C32 modifications in mitochondrial tRNAsThr/Ser(UCN) (mt-tRNAs). This post-transcriptional modification ensures the optimal structure of mt-tRNAs to facilitate efficient translation of mitochondrial proteins involved in electron transport chain (ETC). Although the epitranscriptomic functions of METTL8 have been well characterized, its roles in cancers (i.e. glioblastoma) remain largely unexplored. In this study, we showed that METTL8 is overexpressed in GBM and high METTL8 expression portends poor patient prognosis. In GSC, METTL8 is under the transcriptional regulation of HIF-1α, and the chromatin accessibility at METTL8 promoter is facilitated by the deposition of histone variant H2AZ. METTL8 depletion downregulated m3C32 modifications in mt-tRNAsThr/Ser(UCN) in GSC, leading to impaired mitochondrial translation and OXPHOS defects. Phenotypically, METTL8 knockdown (KD) compromised GSCs’ self-renewal, proliferation, invasiveness and tumorigenicity. Interestingly, METTL8-KD GSC acquired a slow cycling state which is linked to reduced receptor tyrosine kinase (RTK) signaling. Consistently, METTL8-KD GSC showed lower Akt phosphorylation and exhibited increased sensitivity to mTOR/Akt inhibitors. Finally, our mechanistic findings led to the identification of a novel HIF1-α/Akt inhibitor drug combination which faithfully recapitulates the phenotypes of METTL8-KD GSCs. In conclusion, our findings provide the first in-depth study of METTL8 roles in GBM pathogenesis, and highlights a novel drug combination which could potentially be used to treat this dreadful disease. Citation Format: Bernice Woon Li Lee, You Heng Chuah, Jeehyun Yoon, Oleg V. Grinchuk, Jia Feng, Yajing Liang, Jayshree L Hirpara, Ya Ting Shen, Loo Chien Wang, Yan Ting Lim, Tianyun Zhao, Radoslaw M Sobota, Tan Boon Toh, Shazib Pervaiz, Zhewang Lin, Derrick Sek Tong Ong. METTL8-MEDIATED EPITRANSCRIPTOMIC REGULATION OF GBM CYCLING STATE IS DEPENDENT ON RTK/PI3K/AKT SIGNALING [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr LT05.