Lightweight Internet of Things Botnet Detection Using One-Class Classification.

Like smart phones, the recent years have seen an increased usage of internet of things (IoT) technology. IoT devices, being resource constrained due to smaller size, are vulnerable to various security threats. Recently, many distributed denial of service (DDoS) attacks generated with the help of IoT botnets affected the services of many websites. The destructive botnets need to be detected at the early stage of infection. Machine-learning models can be utilized for early detection of botnets. This paper proposes one-class classifier-based machine-learning solution for the detection of IoT botnets in a heterogeneous environment. The proposed one-class classifier, which is based on one-class KNN, can detect the IoT botnets at the early stage with high accuracy. The proposed machine-learning-based model is a lightweight solution that works by selecting the best features leveraging well-known filter and wrapper methods for feature selection. The proposed strategy is evaluated over different datasets collected from varying network scenarios. The experimental results reveal that the proposed technique shows improved performance, consistent across three different datasets used for evaluation.

Correlation between clinical and MRI findings in disc herniation in the lumbosacral region.

AIM OF THE STUDY: To compare clinical findings with MRI findings and evaluate the role of physical examination in the diagnosis, localization of the level, site, size, and type of lumbosacral disc herniation. MATERIALS AND METHODS: A prospective study of 104 patients with low back pain and/or sciatica was conducted et al.-Kindy Teaching Hospital between January to December 2022. All Participants were evaluated via history, clinical examination, and MRI. One hundred patients had a disc herniation in the lumbosacral region, which was confirmed by MRI assessment after clinical presentation and physical examination. The data were collected and analyzed by the chi-square test. RESULTS: Most of the patients (84%) experienced pain in the lower back that radiated to the lower limb or limbs, and nearly half of the patients experienced paresthesia (48%). Sixty-six percent of the patients had a scoliotic list; limitation of lumbar spine movements was common in 96%, and a decrease in the straight leg raising test (SLR) was detected in 98%. Cross SLR "Well test" was positive in 64% of patients. The femoral nerve stretch test was positive in 40% of patients. Sixty-four percent were presented with neurological deficits, 42% with affected L5 nerve roots, 22% with affected S1 nerve roots, and no patients with L4 affected. Twenty-two percent showed a positive SLR test with an angle between 41 and 70°. CONCLUSION: Proper correlation between clinical and MRI will help determine the lesion's level, horizontal location, herniation type, and herniated disc size in the lumbosacral region and achieve a more accurate diagnosis.

Impact of COVID-19 lockdown on air quality analyzed through machine learning techniques.

After February 2020, the majority of the world's governments decided to implement a lockdown in order to limit the spread of the deadly COVID-19 virus. This restriction improved air quality by reducing emissions of particular atmospheric pollutants from industrial and vehicular traffic. In this study, we look at how the COVID-19 shutdown influenced the air quality in Lahore, Pakistan. HAC Agri Limited, Dawn Food Head Office, Phase 8-DHA, and Zeenat Block in Lahore were chosen to give historical data on the concentrations of many pollutants, including PM2.5, PM10 (particulate matter), NO2 (nitrogen dioxide), and O3 (ozone). We use a variety of models, including decision tree, SVR, random forest, ARIMA, CNN, N-BEATS, and LSTM, to compare and forecast air quality. Using machine learning methods, we looked at how each pollutant's levels changed during the lockdown. It has been shown that LSTM estimates the amounts of each pollutant during the lockout more precisely than other models. The results show that during the lockdown, the concentration of atmospheric pollutants decreased, and the air quality index improved by around 20%. The results also show a 42% drop in PM2.5 concentration, a 72% drop in PM10 concentration, a 29% drop in NO2 concentration, and an increase of 20% in O3 concentration. The machine learning models are assessed using the RMSE, MAE, and R-SQUARE values. The LSTM measures NO2 at 4.35%, O3 at 8.2%, PM2.5 at 4.46%, and PM10 at 8.58% in terms of MAE. It is observed that the LSTM model outperformed with the fewest errors when the projected values are compared with the actual values.

Evaluating the role of MEN1 gene expression and its clinical significance in breast cancer patients.

BACKGROUND: Breast cancer is a multifactorial disease which involves number of molecular factors that are critically involved in proliferation of breast cancer cells. MEN1 gene that is traditionally known for its germline mutations in neuroendocrine tumors is associated with high risk of developing breast cancer in females with MEN1 syndrome. However, the paradoxical role of MEN1 is reported in sporadic breast cancer cases. The previous studies indicate the functional significance of MEN1 in regulating breast cells proliferation but its relevance in development and progression of breast cancer is still not known. Our study targets to find the role of MEN1 gene aberration and its clinical significance in breast cancer. METHODS: Breast tumor and adjacent normal tissue of 142 sporadic breast cancer patients were collected at the time of surgery. The expression analysis of MEN1 mRNA and protein was done through RT-PCR, immunohistochemistry and western blotting. Further to find the genetic and epigenetic alterations, automated sequencing and MS-PCR was performed respectively. Correlation between our findings and clinical parameters was determined using appropriate statistical tests. RESULTS: MEN1 expression was found to be significantly increased in the breast tumor tissue with its predominant nuclear localization. The elevated expression of MEN1 mRNA (63.38% cases) and protein (60.56% cases) exhibited a significant association with ER status of the patients. Most of the cases had unmethylated (53.52%) MEN1 promoter region, which can be a key factor responsible for dysregulated expression of MEN1 in breast cancer cases. Our findings also revealed the significant association of MEN1 mRNA overexpression with Age and lymph node status of the patients. CONCLUSION: Our results indicate upregulated expression of MEN1 in sporadic breast cancer patients and it could be critically associated with development and advancement of the disease.

Antibody-drug conjugates: the paradigm shifts in the targeted cancer therapy.

Cancer is one of the deadliest diseases, causing million of deaths each year globally. Conventional anti-cancer therapies are non-targeted and have systemic toxicities limiting their versatile applications in many cancers. So, there is an unmet need for more specific therapeutic options that will be effective as well as free from toxicities. Antibody-drug conjugates (ADCs) are suitable alternatives with the right potential and improved therapeutic index for cancer therapy. The ADCs are highly precise new class of biopharmaceutical products that covalently linked a monoclonal antibody (mAb) (binds explicitly to a tumor-associated surface antigen) with a customized cytotoxic drug (kills cancer cells) and tied via a chemical linker (releases the drug). Due to its precise design, it brings about the target cell killing sparing the normal counterpart and free from the toxicities of conventional chemotherapy. It has never been so easy to develop potential ADCs for successful therapeutic usage. With relentless efforts, it took almost a century for scientists to advance the formula and design ADCs for its current clinical applications. Until now, several ADCs have passed successfully through preclinical and clinical trials and because of proven efficacy, a few are approved by the FDA to treat various cancer types. Even though ADCs posed some shortcomings like adverse effects and resistance at various stages of development, with continuous efforts most of these limitations are addressed and overcome to improve their efficacy. In this review, the basics of ADCs, physical and chemical properties, the evolution of design, limitations, and future potentials are discussed.

Therapeutic importance of Kigelia africana subsp. africana: an alternative medicine.

AIM: To summarise a detailed up-to-date review of the traditional uses, phytoconstituents, and pharmacological activities of various parts of Kigelia africana. MATERIALS AND METHODS: Google Scholar, PubMed, PubChem, Elsevier, King Draw, indianbiodiversity.org. RESULT: The phytochemical analysis of Kigelia africana subsp. africana has revealed the presence of approximately 145 compounds extracted from different parts of the plant. These bioactive extracts of the plant possess anti-inflammatory, antioxidant, antimicrobial, antidiabetic, antineoplastic, and anti-urolithic activities. Due to its anti-inflammatory, antioxidant, and immune-booster properties, Kigelia can prove to be an essential source of drugs for treating various disorders. CONCLUSION: Knowledge of the phytoconstituents, non-medicinal and medicinal traditional uses, pharmacological activities, and products obtained from Kigelia is described in this review with the hope that the updated findings will promote research on its biological pathways.

Traditional medicinal importance of Kigelia africana subsp. africanaPhytoconstituents present in extracts from different parts of the plantPharmacological activities of phytochemicals extracted from KigeliaAnti-inflammatory and antioxidant role in preventing oxidative stressPotential as ethnopharmacological therapeutic in treating respiratory ailmentsToxicity evaluation of Kigelia africana subsp. africana.

Phytocompounds targeting epigenetic modulations: an assessment in cancer.

For centuries, plants have been serving as sources of potential therapeutic agents. In recent years, there has been a growing interest in investigating the effects of plant-derived compounds on epigenetic processes, a novel and captivating Frontier in the field of epigenetics research. Epigenetic changes encompass modifications to DNA, histones, and microRNAs that can influence gene expression. Aberrant epigenetic changes can perturb key cellular processes, including cell cycle control, intercellular communication, DNA repair, inflammation, stress response, and apoptosis. Such disruptions can contribute to cancer development by altering the expression of genes involved in tumorigenesis. However, these modifications are reversible, offering a unique avenue for therapeutic intervention. Plant secondary compounds, including terpenes, phenolics, terpenoids, and sulfur-containing compounds are widely found in grains, vegetables, spices, fruits, and medicinal plants. Numerous plant-derived compounds have demonstrated the potential to target these abnormal epigenetic modifications, including apigenin (histone acetylation), berberine (DNA methylation), curcumin (histone acetylation and epi-miRs), genistein (histone acetylation and DNA methylation), lycopene (epi-miRs), quercetin (DNA methylation and epi-miRs), etc. This comprehensive review highlights these abnormal epigenetic alterations and discusses the promising efficacy of plant-derived compounds in mitigating these deleterious epigenetic signatures in human cancer. Furthermore, it addresses ongoing clinical investigations to evaluate the therapeutic potential of these phytocompounds in cancer treatment, along with their limitations and challenges.

Chrysin and Capsaicin induces premature senescence and apoptosis via mitochondrial dysfunction and p53 elevation in Cervical cancer cells.

Current studies are focusing on the anti-cancerous properties of natural bioactive compounds, primarily those included in the human diet. These compounds have the potential to alter the redox balance that can hinder cancer cell's growth. In cancer cells, an abnormal rate of ROS production is balanced with higher antioxidant activities, which if not maintained, results in cancer cells being prone to cell death due to oxidative stress. Here, we have analyzed the effects of Chrysin and Capsaicin on the HeLa cells viability and cellular redox signaling. Both these compounds stimulate cellular and mitochondrial ROS overproduction that perturbs the cellular redox state and results in mitochondrial membrane potential loss. Apart from this, these compounds induce cell cycle arrest and induce premature senescence, along with the overexpression of p21, p53, and p16 protein at lower concentration treatment of Chrysin or Capsaicin. Moreover, at higher concentration treatment with these compounds, pro-apoptotic activity was observed with the high level of Bax and cleaved caspase-3 along with suppression of the Bcl-2 protein levels. In-Silico analysis with STITCH v5 also confirms the direct interaction of Chrysin and Capsaicin with target protein p53. This suggests that Chrysin and Capsaicin trigger an increase in mitochondrial ROS, and p53 interaction leading to premature senescence and apoptosis in concentration dependent manner and have therapeutic potential for cancer treatment.

Plant metabolite diosmin as the therapeutic agent in human diseases.

Plant-derived flavonoids have been the focus of research for many years mainly in the last decade owing to their therapeutic properties. So far, about 4000 flavonoids have been identified from plants and diosmin (a flavone glycoside) is one of them. Online databases, previous studies, and reviews have been used to gather information on anti-oxidant, immunomodulatory, anti-cancer, anti-parasitic, and anti-microbialproperties of diosmin. Effects of diosmin in combination with other flavonoids have been reviewed thoroughly and its administrative routes are also summarized. Additionally, we studied the effect of diosmin on critical protein networks. It exhibits therapeutic effects in diabetes and its associated complications such as neuropathy and dyslipidemia. Combination of diosmin with hesperidin is found to be very effective in the treatment of chronic venous insufficiency and haemorrhoids. Diosmin is an exquisite therapeutic agent alone as well as in combination with other flavonoids.

Factors Influencing the Adoption of IoT for E-Learning in Higher Educational Institutes in Developing Countries.

The internet of things (IoT) is an emerging paradigm of educational applications and innovative technology in the current era. While capabilities are increasing day by day, there are still many limitations and challenges to utilizing these technologies within E-Learning in higher educational institutes (HEIs). The IoT is well-implemented in the United States of America (USA), United Kingdom (UK), Japan, and China but not in developing countries, including Saudi Arabia, Malaysia, Pakistan, Bangladesh, etc. Few studies have investigated the adoption of IoT in E-Learning within developing countries. Therefore, this research aims to examine the factors influencing IoT adoption for E-Learning to be utilized in HEIs. Further, an adoption model is proposed for IoT-based E-Learning in the contexts of developing countries and provides recommendations for enhancing the IoT adoption for E-Learning in HEIs. The IoT-based E-Learning model categorizes these influencing factors into four groups: individual, organizational, environmental, and technological. Influencing factors are compared along with a detailed description in order to determine which factors should be prioritized for efficient IoT-based E-Learning in HEIs. We identify the privacy (27%), infrastructure readiness (24%), financial constraints (24%), ease of use (20%), support of faculty (18%), interaction (15%), attitude (14%), and network and data security (14%), as the significant E-Learning influencing factors on IoT adoption in HEIs. These findings from the researcher's perspective will show that the national culture has a significant role in the individual, organizational, technological, and environmental behavior toward using new technology in developing countries.

FOXO1 Gene Downregulation and Promoter Methylation Exhibits Significant Correlation With Clinical Parameters in Indian Breast Cancer Patients.

Background: Forkhead box "O" one which is member of Forkhead box family of transcription factors is known to play key role in different physiological processes including cell cycle arrest, autophagy, and apoptosis. FOXO1 is defined to play tumor suppressive role in various malignancies including breast cancer and its Dysregulation is frequently reported. However, the evaluation of FOXO1 promoter methylation and its expression at mRNA and protein level in different stages of breast cancer and its association with different clinical parameters is still not studied. Therefore, for better understanding the role of FOXO1 in breast cancer, in our study we examined the FOXO1 mRNA and protein expression in Breast cancer samples of Indian breast cancer patients. Results: Total 127 breast cancer samples along with adjacent normal tissue (n = 127) were analyzed through methylation specific PCR (MS-PCR), mRNA expression (Real-time PCR) and Immunohistochemistry (IHC). We detected 69.29% cases to be downregulated at the mRNA level, and 77.95% of cases exhibited no or low protein expression. In our data we report a significant association (p = 0.0001) between the downregulated protein expression and promoter hypermethylation of FOXO1 gene. We also found a significant correlation of FOXO1 mRNA level with Age (p = 0.008), age at first live birth (p = 0,003), tumor size (p = 0.05) and lymph node status (p = 0.01). Conclusion: we in our study report the tumor suppressive role of FOXO1 in case of Indian breast cancer patients and our data suggest it to exhibit prognostic importance. However, further research is needed to evaluate FOXO1 significance in diagnostic and therapeutic targeting in breast cancer cases.

Clinical effectiveness of tenotomy versus tenodesis for long head of biceps pathology: a systematic review and meta-analysis.

OBJECTIVES: The comparative clinical effectiveness of common surgical techniques to address long head of biceps (LHB) pathology is unclear. We synthesised the evidence to compare the clinical effectiveness of tenotomy versus tenodesis. DESIGN: A systematic review and meta-analysis using the Grading of Recommendations Assessment, Development and Evaluation approach. DATA SOURCES: EMBASE, Medline, PsycINFO and the Cochrane Library of randomised controlled trials were searched through 31 October 2021. ELIGIBILITY CRITERIA: We included randomised controlled trials, reporting patient reported outcome measures, comparing LHB tenotomy with tenodesis for LHB pathology, with or without concomitant rotator cuff pathology. Studies including patients treated for superior labral anterior-posterior tears were excluded. No language limits were employed. All publications from database inception to 31 October 2021 were included. DATA EXTRACTION AND SYNTHESIS: Screening was performed by two authors independently. A third author reviewed the article, where consensus for inclusion was required. Data were extracted by two authors. Data were synthesised using RevMan. Inverse variance statistics and a random effects model were used. RESULTS: 860 patients from 11 RCTs (426 tenotomy vs 434 tenodesis) were included. Pooled analysis of patient-reported functional outcome measures data demonstrated comparable outcomes (n=10 studies; 403 tenotomy vs 416 tenodesis; standardised mean difference (SMD): 0.14, 95% CI -0.04 to 0.32, p=0.13). There was no significant difference for pain (Visual Analogue Scale) (n=8 studies; 345 tenotomy vs 350 tenodesis; MD: -0.11, 95% CI -0.28 to 0.06, p=0.21). Tenodesis resulted in a lower rate of Popeye deformity (n=10 studies; 401 tenotomy vs 410 tenodesis; OR: 0.29, 95% CI 0.19 to 0.45, p<0.00001). Tenotomy demonstrated shorter operative time (n=4 studies; 204 tenotomy vs 201 tenodesis; MD 15.2, 95% CI 1.06 to 29.36, p<0.00001). CONCLUSIONS: Aside from a lower rate of cosmetic deformity, tenodesis yielded no significant clinical benefit to tenotomy for addressing LHB pathology. PROSPERO REGISTRATION NUMBER: CRD42020198658.

FOXO3 gene hypermethylation and its marked downregulation in breast cancer cases: A study on female patients.

Background: FOXO3, a member of the FOX transcription factor family, is frequently described as being deregulated in cancer. Additionally, notable role of FOXO3 can be easily recognized in the process of ageing and survival. Even though various studies have been done to acknowledge the tumour-suppressive or oncogenic role of FOXO3 in cancer, still there exist a lack of understanding in terms of cancer prognosis and treatment. Therefore, to provide better insight, our study aims to evaluate the role and function of FOXO3 in breast cancer in Indian female patients. We examined the FOXO3 expression levels in breast cancer samples by analyzing mRNA and protein expression along with its clinicopathological parameters. Results: A total of 127 cases of breast cancer with equal normal cases (n=127) were assessed with methylation (MS-PCR), Immunohistochemistry (IHC), mRNA expression using Real-time PCR was analysed and 66.14% cases at mRNA level were found to be downregulated, while 81.10% of cases had little or very little protein expression. Our data state, the promoter hypermethylation of the FOXO3 gene and the downregulated protein expression are significantly correlated (p=0.0004). Additionally, we found a significant correlation between the level of FOXO3 mRNA with ER (p=0.04) and status of lymph node (p=0.01) along with this. Conclusion: Data suggests the prognostic significance and the tumour-suppressive role of FOXO3 in breast cancer cases studied in India. However, there is a need for the extended research targeting FOXO3 to measure its clinical potential and develop well-defined therapeutic strategies.

Fucoidan induces ROS-dependent epigenetic modulation in cervical cancer HeLa cell.

Fucoidan is a sulfated polysaccharide obtained from marine algae and known for various pharmacological activities. In this study, we investigated the effect of Fucoidan on cell viability, redox balance, cytoskeletal component F-actin, HDAC inhibition, autophagy, and senescence phenomenon in human cervical cancer HeLa cell line in comparison to positive control suberoylanilide hydroxamic acid by flow cytometry, fluorescence microscopy, and western blotting. Our observations revealed that Fucoidan exposure induces cytotoxicity in HeLa cells via ROS and mitochondrial superoxide generation and loss of ATP. Colorimetrical studies suggested that Fucoidan impairs the function of HDAC expression. Fucoidan treatment also contributes to the change in the granularity of cells, senescence-associated heterochromatin foci formation that leads to senescence in HeLa cells. Moreover, we visualize that Fucoidan exhibits autophagosomes formation with monodansylcadaverine, and flow cytometry analysis by acridine orange further substantiates that Fucoidan triggers autophagy in HeLa cells. Additionally, the changes in the expression of proteins p21, p16, BECN1, and HDAC1 were seen as markers of senescence, autophagy, and HDAC inhibition by FACS and immunoblotting. Molecular docking study validates Fucoidan-HDAC1 association in corroboration with the experimental data. Collectively, these mechanistic studies demonstrated that Fucoidan could be a therapeutic molecule for targeting HDACs in cervical cancer.

Buffalo Infection by Fasciola gigantica Transmitted by Radix acuminata in Uttar Pradesh, India: A Molecular Tool to Improve Snail Vector Epidemiology Assessments and Control Surveillance.

PURPOSE: Fascioliasis is caused by Fasciola species transmitted by freshwater Lymnaeidae snails and infecting herbivorous mammals and humans worldwide. In southern Asia, fascioliasis is a problem in livestock from the Near East to Bangladesh, where recent human infection reports are worrying. In this region, Fasciola gigantica is transmitted by species of the Radix auricularia superspecies group. In the densely populated northern Indian state of Uttar Pradesh, livestock appears infected throughout. The economic importance of buffaloes highlights the need to control their very high infection rates. METHODS: In the Gorakhpur area, a molecular method based on the two specific primer sets of genomic DNA was applied to fasciolids from buffaloes slaughtered in local abattoirs and cercariae from R. acuminata snails from freshwater collections. RESULTS: PCR products and sequences demonstrated that the cercariae belonged to F. gigantica and that R. acuminata acts as vector for its transmission to buffaloes. The 72.0% rate found in one transmission focus appears to be the highest worldwide record of fasciolid infection in a lymnaeid population. Lymnaeid prevalences and burdens found close to human communities indicate a very high infection risk. CONCLUSION: This method is simple, fast and cheap because there is no need for sequencing, it differentiates between fasciolid species and between fasciolids and other trematodes infecting R. acuminata, facilitates epidemiological surveys, and is useful for surveillance to evaluate the efficiency of control measures. Within climate change predictions, future increases of rain events and floods suggest the need for control and surveillance efforts in this endemic area.

The Educational Environment Is Warming Up: Response to Changes in a Component of a Medical Curriculum.

INTRODUCTION: The Dundee Ready Educational Environment Measure (DREEM) is a valid instrument to evaluate the educational environment of institutions. This quantitative study aimed to discover if applying interactive educational approaches to a component of a traditionally taught medical curriculum improved the educational environment, as measured by the DREEM. METHODS: The bilingual Arabic-English DREEM questionnaire was distributed twice to all third-year medical students (273 students) at the Hashemite University in Jordan. The first data collection occurred at the completion of a traditionally taught component of the Neurology module and the second data collection at the end of an interactively taught component of the same module. A paired t-test was used to compare the results. RESULTS: The total DREEM score for the innovative interactive course was 120.04/200 (from 183 questionnaires) and for the traditionally taught course was 114.69/200 (from 198 questionnaires). Of the five DREEM sub-scales, the interactive course scored statistically significantly higher than the traditionally taught course for "perceptions of learning" and "perceptions of atmosphere" (p-value 0.013 and 0.011, respectively). The interactively taught course was particularly valued by students for being participative, student-centered, and developing their professional competence. The lowest scoring item for both courses was "there is a good support system for students who get stressed." DISCUSSION: This study demonstrated that students value interactive learning environments and that there is benefit in introducing these components to a traditionally taught medical curriculum, when it may not be feasible to bring innovation to the entire medical curriculum due to resource constraints. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01359-y.

Unusual histopathological findings in appendectomy specimens with clinical diagnosis of acute appendicitis: A retrospective cohort analysis.

INTRODUCTION: While appendicitis is considered one of most common acute surgical conditions, several studies have reported abnormal histopathological findings in appendectomy specimens; however, sending all appendices to histopathology is not yet routinely done.Here we report many unusual findings. Those unusual findings played a role not only in confirming acute appendicitis as a cause of the presentation in some cases but also discovering etiologies that mimic it with great impact on its management. METHODS: Between January 2011 and December 2017, a total of 1510 patients were operated with appendectomy for a primary diagnosis of acute appendicitis. Among them, a total of 72 patients had incidental histopathologic findings in association with acute appendicitis or other pathologies instead of acute appendicitis. A retrospective analysis for those 72 patients was performed with all data being retrieved from the electronic health record system. RESULTS: Patients ages ranged between 4 and 71 years with a mean age equal to 23.1 years (SD = 14.2). Majority of patients were women (n = 52; 72.2%). Sixty of the seventy-two cases were seen in patients with negative appendectomies (n = 333) with an overall rate of 18% among this group of patients. The remaining 12 patients had additional findings in histopathology specimens beside acute appendicitis (n = 1131) with an overall rate of 1%. The most commonly reported pathologies were serositis, ovarian cysts, and Enterobius vermicularis in descending frequency. CONCLUSION: Identification of unusual histopathological findings during microscopic examination of resected appendices is more common in female patients and in patients with negative appendectomy. histopathologic assessment of specimens will allow detection of congenital, infectious or malignant pathologies that mimic acute appendicitis clinically even in the absence appendicitis microscopically.

LC-MS and docking profiling reveals potential difference between the pure and crude fucoidan metabolites.

Fucoidan, a macromolecule, a type of polysaccharide and contains high percentage of fucose and sulfate ester groups and other compounds in low percentage. In the last decades, a number of interesting biological activities have been studied so fucoidan has been major focus of interest for exploring new drugs against the leading human diseases. It is known in relation to biological pathways and function that it activates the pathways which mediate apoptosis. Using LC-MS and interdisciplincary approach, we developed our goal to elucidate the potential difference between the crude and pure fucoidan and the interaction of fucoidan with potential signaling molecules STAT4 and IL12RB2. Based on our analysis, we conclude that there is major difference between crude and pure fucoidan in terms of identified metabolites and their functional relevance. It leads to the conclusion that there are 18 functions which are common between crude and pure fucoidans, 47 functions pure fucoidan specific, and 84 functions crude fucoidan specific which leads to the conclusion that even the fucoidans obtained from the same organism behave functionally completely different between the processing states (with/without processing) while docking study with STAT4 and IL12RB2 display very strong binding between fucoidan and both these signaling molecules.

Exploring the p53 connection of cervical cancer pathogenesis involving north-east Indian patients.

BACKGROUND: As per WHO, Cervical cancer (CaCx) is a global issue, being the fourth common cancer in women with incidence rate of 13.1 per 1 lakh women globally and accounting for 311000 deaths in the year 2018 itself globally. The molecular pathogenesis in Human papillomavirus (HPV) infected cases is inconclusive. The detection of molecular factors leading to progression of CaCx can be important in the diagnosis and management of the disease. p53 a known tumor suppressor gene having a regulative role in cell cycle has been highlighted as key factor in the prevention of cancer but its significance in CaCx cases has been variably documented. The present study therefore targeted to evaluate the significance of p53 profile in CaCx cases in ethnically distinct northeast Indian population. METHODS: Blood and Tissue samples (N = 85) of cervical cancer patients were collected and screening for HPV was performed using PCR. Thereafter the differential mRNA expression(qPCR), Immunohistochemistry, Mutation (PCR direct sequencing method) of p53 was studied. Further p53 epigenetic profiling was done by Methylation specific PCR (MS-PCR) and western blotting by using p53 acetylation specific antibodies. RESULTS: Our findings revealed that the downregulation of p53 was associated with the progression of disease and the variation in downregulation based on p53 polymorphism was observed. Further hypermethylation and deacetylation of p53 was also found to be associated with the pathogenesis of CaCx. The downregulated expression and hypermethylation of p53 in lower grade of CaCx, together established its association with the progression of CaCx from lower to severe grade. CONCLUSION: Therefore, in CaCx patients of northeast Indian population, malfunctioning of p53 is found to have significant role in cervical cancer progression.