Efficacy of emicizumab in von Willebrand disease (VWD) patients with and without alloantibodies to von Willebrand factor (VWF): Report of two cases and review of literature.

INTRODUCTION: von Willebrand disease (VWD) is the common bleeding disorder with a clinically relevant bleeding prevalence of 1:10,000. von Willebrand disease patients lack both von Willebrand factor (VWF) and factor VIII (FVIII), which are critical for normal haemostasis. The conventional treatment for VWD includes desmopressin and replacement therapy with plasma derived FVIII with VWF concentrates or recombinant VWF. Development of alloantibodies is a rare occurrence, there is a paucity in the literature of treatment modalities in these patients. Not many reports are available in literature on the efficacy of emicizumab in VWD patients with or without alloantibodies to VWF. AIM: To do systematic review of literature on emicizumab in VWD and report our experience of emicizumab in two patients of VWD METHODS: We used electronic search engines till May 2021 in 'Google scholar' and 'PubMed', to collect the case reports or case series on use of emicizumab for management of VWD. Two of our severe VWD patients were successfully treated with emicizumab. A systematic review was performed and the results discussed. RESULTS: The electronic search revealed six case reports using emicizumab for treatment of VWD. Two were in vitro studies and four in patients with VWD type 3 disease. In vitro studies and in VWD patients on emicizumab, showed improvement in thrombin generation and fibrin formation. Among four patients, three had alloantibodies to VWD and one was negative. All these patients were treated with emicizumab for 6-12 m. After starting emicizumab, none of them had spontaneous bleeding requiring treatment. During treatment with emicizumab, one patient had trauma-associated soft tissue hematoma, which was treated with rFVIIa and another patient had bleeding following dental exfoliation treated with Humate P. We treated two of our VWD patients one with and one without inhibitors with emicizumab after failure of other therapies. Both the patients showed marked improvement and continued to remain well and free of bleeding episodes. None of the patients had any thrombosis or thrombotic microangiopathy (TMA) during treatment with emicizumab. CONCLUSION: In conclusion, this review supports the safety and efficacy of emicizumab in type 3 VWD patients with or without alloantibodies. Further large studies are required to confirm the safety and efficacy of emicizumab in VWD.

Automatic detection of COVID-19 in chest radiographs using serially concatenated deep and handcrafted features.

Since the infectious disease occurrence rate in the human community is gradually rising due to varied reasons, appropriate diagnosis and treatments are essential to control its spread. The recently discovered COVID-19 is one of the contagious diseases, which infected numerous people globally. This contagious disease is arrested by several diagnoses and handling actions. Medical image-supported diagnosis of COVID-19 infection is an approved clinical practice. This research aims to develop a new Deep Learning Method (DLM) to detect the COVID-19 infection using the chest X-ray. The proposed work implemented two methods namely, detection of COVID-19 infection using (i) a Firefly Algorithm (FA) optimized deep-features and (ii) the combined deep and machine features optimized with FA. In this work, a 5-fold cross-validation method is engaged to train and test detection methods. The performance of this system is analyzed individually resulting in the confirmation that the deep feature-based technique helps to achieve a detection accuracy of > 92% with SVM-RBF classifier and combining deep and machine features achieves > 96% accuracy with Fine KNN classifier. In the future, this technique may have potential to play a vital role in testing and validating the X-ray images collected from patients suffering from the infection diseases.

Perceptions on COVID-19 Vaccination among People Aged more than 50 years in Urban Field Practice Area of Department of Community Medicine in a Tertiary Care Teaching Hospital, Hyderabad: A Reflection from Focus Group Discussions.

Background: Despite several efforts to limit the viral transmission, the COVID-19 vaccine has been the only "the ray of hope" to end the pandemic. However, vaccine hesitancy could reduce coverage and hinder herd immunity. People's intention to get vaccinated can be shaped by several factors, including risk perception which, in turn, is influenced by effect. The need to acquaint oneself to the beliefs, concerns, and circumstances of one's own population in the community becomes important for successful implementation of the program. Therefore, the present study was conducted to gain insights into perceptions of vaccination. Objectives: The objective is to understand the felicitating factors and hindering factors for acceptance of vaccines by the population among people aged 50 years in urban field practice area of the Department of Community Medicine in a Tertiary care teaching hospital, Hyderabad. Subjects and Methods: Data were extracted from audio recording of five focus group discussions that were conducted in the urban field practice care of a tertiary care teaching hospital in Hyderabad through open-ended questions. Categories, subcategories, and themes were created by deductive approach. Results: The motivating factors for vaccine acceptance were found to be fear of getting disease, wanting to return normalcy, and trust in treating doctors, whereas, barriers were fear of death due to vaccine, opacity in vaccine details, anxiety, and misinterpretation of adverse events. Conclusion: Having a clear understanding about the belief system of the target population could help in designing the guidelines for vaccination program to escalate the immunization and increase the acceptance.

Oral metronomic chemotherapy after definitive chemoradiation in esophageal squamous cell carcinoma: a randomized clinical trial.

BACKGROUND: Improving outcomes in locally advanced esophageal/GEJ squamous cell cancer (SCC) is an unmet need. We investigated the addition of oral metronomic chemotherapy (OMC) following definitive chemoradiotherapy (CRT). MATERIALS AND METHODS: This was a randomized open-label integrated phase II/III study in patients with SCC of esophagus/GEJ following definitive CRT who had no radiologic evidence of progression, and no endoscopically detected disease. Randomization was 1:1 to OMC (celecoxib 200 mg twice daily and methotrexate 15 mg/m2 weekly) for 12 months or observation. The primary endpoint for the phase II portion was progression-free survival (PFS); secondary endpoints were overall survival (OS) and toxicity. P ≤ 0.2 for PFS was required to proceed to phase III. RESULTS: Between Jan 2016 and Dec 2019, we enrolled 151 patients for the phase II portion, 75 to OMC and 76 to observation. The tumor originated in the upper thoracic esophagus in 79% patients. Concurrent CRT consisted of median 63 Gy in a median of 35 fractions; concurrent chemotherapy was weekly paclitaxel + carboplatin in 91%. OMC was started at a median of 2.6 months (IQR 2.3-2.8) from CRT completion. Grade 3 or higher toxicities occurred in 18 patients (24%) in the OMC arm and 9 (12%) in the observation arm; P = 0.071. Median PFS was 25 months (95% CI, 17-58) in the OMC arm and was not attained [NA] (95% CI, 25-NA) in the observation arm; HR, 1.51, 95% CI, 1-2; P = 0.073. Median OS was 36 months (95% CI, 23-NA) in the OMC arm, and not attained (95% CI, NA-NA) in the observation arm; HR, 1.77; 95% CI, 1-2.9; P = 0.023. CONCLUSION: Oral metronomic methotrexate and celecoxib in patients who have not progressed radiologically and have no endoscopic evidence of disease following radical CRT for locally advanced esophageal/GEJ SCC does not improve outcomes and may lower survival. [Funded by the TMC-Research Administration Council (TRAC); CHROME study (CHemoRadiotherapy followed by Oral Metronomic therapy in Esophageal cancer); ctri.nic.in number: CTRI/2015/09/006204]. TRIAL REGISTRATION NUMBER: CTRI/2015/09/006204.

Neuroprotective effects of a dendrimer-based glutamate carboxypeptidase inhibitor on superoxide dismutase transgenic mice after neonatal hypoxic-ischemic brain injury.

The result of a deprivation of oxygen and glucose to the brain, hypoxic-ischemic encephalopathy (HIE), remains the most common cause of death and disability in human neonates globally and is mediated by glutamate toxicity and inflammation. We have previously shown that the enzyme glutamate carboxypeptidase (GCPII) is overexpressed in activated microglia in the presence of inflammation in fetal/newborn rabbit brain. We assessed the therapeutic utility of a GCPII enzyme inhibitor called 2-(3-Mercaptopropyl) pentanedioic acid (2MPPA) attached to a dendrimer (D-2MPPA), in order to target activated microglia in an experimental neonatal hypoxia-ischemia (HI) model using superoxide dismutase transgenic (SOD) mice that are often more injured after hypoxia-ischemia than wildtype animals. SOD overexpressing and wild type (WT) mice underwent permanent ligation of the left common carotid artery followed by 50 min of asphyxiation (10% O2) to induce HI injury on postnatal day 9 (P9). Cy5-labeled dendrimers were administered to the mice at 6 h, 24 h or 72 h after HI and brains were evaluated by immunofluorescence analysis 24 h after the injection to visualize microglial localization and uptake over time. Expression of GCPII enzyme was analyzed in microglia 24 h after the HI injury. The expression of pro- and anti-inflammatory cytokines were analyzed 24 h and 72 h post-HI. Brain damage was analyzed histologically 7 days post-HI in the three randomly assigned groups: control (C); hypoxic-ischemic (HI); and HI mice who received a single dose of D-2MPPA 6 h post-HI (HI+D-2MPPA). First, we found that GCPII was overexpressed in activated microglia 24 h after HI in the SOD overexpressing mice. Also, there was an increase in microglial activation 24 h after HI in the ipsilateral hippocampus which was most visible in the SOD+HI group. Dendrimers were mostly taken up by microglia by 24 h post-HI; uptake was more prominent in the SOD+HI mice than in the WT+HI. The inflammatory profile showed significant increase in expression of KC/GRO following injury in SOD mice compared to WT at 24 and 72 h. A greater and significant decrease in KC/GRO was seen in the SOD mice following treatment with D-2MPPA. Seven days after HI, D-2MPPA treatment decreased brain injury in the SOD+HI group, but not in WT+HI. This reduced damage was mainly seen in hippocampus and cortex. Our data indicate that the best time point to administer D-2MPPA is 6 h post-HI in order to suppress the expression of GCPII by 24 h after the damage since dendrimer localization in microglia is seen as early as 6 h with the peak of GCPII upregulation in activated microglia seen at 24 h post-HI. Ultimately, treatment with D-2MPPA at 6 h post-HI leads to a decrease in inflammatory profiles by 24 h and reduction in brain injury in the SOD overexpressing mice.

Piperazinyl-Based Diamide Ligand for Selective Precipitation of Actinyl (UO22+/PuO22+) Ions with Fast Kinetics.

A novel ligand N,N'-bis(N″,N″-diethyl carbamoyl) piperazine (BDECP), L1, is synthesized as a selective precipitant for hexavalent actinyl (UO22+ and PuO22+) ions from an aqueous nitric acid medium. The ligand BDECP forms an infinite one-dimensional coordination polymer with uranyl nitrate and behaves as a bridging bidentate neutral donor. There is an alternate repetition of [UO2(NO3)2] and BDECP units as evidenced by single-crystal X-ray diffraction. Uranyl ion (UO22+) can be precipitated in >99% yield from an aqueous nitric acid medium. L1 shows fast kinetics of precipitation of uranyl ion as compared to those of other reported ligands like N-alkyl pyrolidone and N-(1-adamantyl) acetamide. Avrami's coefficient, obtained from the Avrami-Erofe'ev equation, shows that the precipitation mechanism is controlled by the phase boundary and not governed by diffusion. Theoretical studies of the uranyl complex of L1 show that there is no thermodynamic preference for L1 as compared to other potential amide-based precipitants. The principal factors that govern the fast kinetics of precipitation are the aqueous solubility and higher charge density on the amide oxygen of L1.

Role of microbial dysbiosis in carcinogenesis & cancer therapies.

The human body supports a heterogeneous population of microorganisms. Every microorganism has the ability to contribute to the unique microenvironment around it. The aim of this review is to discuss the changes in the microbial population and their relative abundance across different ecosystems of the human body, the interactions within the microbial communities, metabolites they secrete to their external environment, their immunomodulatory functions, their signal transduction pathways and how these respond to environmental stimuli such as various diets, alcohol and drug consumption, smoking and finally suggest new therapeutic approaches. The microbiota may leads to cancer through inflammation mediated mechanisms which modulate immune responses, or produce carcinogenic metabolites and genotoxins, or deregulate cell proliferative signalling pathways. The identification of these molecular mechanisms in carcinogenesis may lead to better treatment strategies. In this review we have tried to explore the changes in microbial composition between cancer and normal tissues and what molecular mechanisms provide a connecting link between microbial dysbiosis and cancer.

Prevalence of Periodontal Disease among Obese Young Adult Population in Saudi Arabia-A Cross-Sectional Study.

Background and objectives: We aimed to assess the prevalence of periodontal disease among obese young adults in Saudi Arabia and to analyze the association between different body mass indexes and the severity of periodontal disease. Materials and methods: This descriptive cross-sectional study consisted of 307 obese patients aged 18-39 years, with body mass index (BMI) ≥30. Demographic variables for periodontal disease, anthropometric parameters such as BMI along with clinical parameters such as oral hygiene index-simplified, community periodontal index (CPI) score and loss of attachment (LOA), were assessed. Multivariate binary logistic regression analysis was used to identify the predictors for chronic periodontitis in obese young adults between 18-40 years of age. Results: The majority of the participants (71.3%) had periodontal disease. Obese and extremely obese patients together showed a statistically significant difference in the age group of 21-30 years in terms of CPI score for inflammation (p < 0.05) and LOA (p < 0.001). Logistic regression analysis showed age (OR: 3.180; 95%CL: 1.337-7.561; p <.001), occasional dental visit (OR: 5.965; 95%CL: 3.130-11.368; p < 0.001), smoking >10 cigarettes (OR: 11.868; 95%CL: 3.588-39.254; p < 0.001) and poor oral hygiene status (OR: 17.250; 95%CL: 6.958-42.764; p < 0.001) were associated with a significantly higher risk of having periodontal disease. Conclusions: This study showed a high prevalence of periodontal disease in obese patients among the Saudi Arabian population.

Spiritual Care: Define and Redefine Self.

Spiritual care is deep rooted in the traditional ancient system of medicine. However, due to lack of high grade evidences, practitioners of modern system of medicine are hesitant to inculcate spirituality in their clinical practice. This paper is an attempt to basic understanding of spiritual care therapy, current evidences for it and the challenges for incorporation in the allopathic system of medicine.

Prevalence of FVIII inhibitors in severe haemophilia A patients: Effect of treatment and genetic factors in an Indian population.

INTRODUCTION: Factor replacement therapy in treatment of haemophilia A is complicated by the production of neutralising antibodies known as inhibitors. The formation of inhibitors is multifactorial being associated with both genetic and environmental factors. AIM: To document the prevalence of inhibitors in severe haemophilia in the community where most patients receive only infrequent episodic replacement therapy and evaluate the factors which could be contributing to it. METHODS: Community based camps were conducted in different parts of the country. Patients were assessed through a structured questionnaire and blood samples were obtained for laboratory evaluation of inhibitors and defined immunological parameters. RESULTS: Inhibitors were present in 87/447 (19.5%) of the evaluated patients. High-titre inhibitor (>5 Bethesda Units [BU]) was identified in 31 (35.6%) patients. HLA DRB1-13-positive cases (RR = 2.04; 95% CI 1.06-3.911; P = 0.033) had an increased risk of inhibitor formation which was retained in the high-titre subset. A decreased risk of inhibitor formation was noted with heterozygous IL4-590 C/T allele (RR = 0.22; 95% CI 0.108-0.442: P = 0.000). There were no significant correlations between any of the evaluated environmental factors and the development of inhibitors in this study. CONCLUSION: The overall prevalence of inhibitors in patients with severe haemophilia A is similar to that reported among patients receiving regular replacement therapy. The data from this study, limited by its retrospective and cross-sectional study design, would suggest that genetic rather than environmental are more likely to impact the development of inhibitors.

Purification, crystallization and anticancer activity evaluation of the compound alternariol methyl ether from endophytic fungi Alternaria alternata.

AIMS: Medicinal plant-associated endophytic fungi are important sources of precious bioactive compounds, contributing more than 80% of the natural drugs for various ailments. The present study was aimed at evaluating the anticancer activity of the crystallized compound alternariol methyl ether (AME) against hepatocellular carcinoma (HCC) both in vitro and in vivo from an endophytic fungus residing in the medicinal plant Vitex negundo. METHODS AND RESULTS: The secondary metabolites from the endophytic fungus Alternaria alternata MGTMMP031 were isolated. Purification and characterization of the compound was performed and the potential compound was identified as AME. The crystal structure of AME was unambiguously confirmed by X-ray analysis. AME has been checked for its antibacterial and anticancer properties which showed its effectiveness against various bacteria and demonstrated marked anti-proliferative activity against the human HCC cells (HUH-7) both in vitro and in vivo. Mode of actions included cell cycle arrest, reducing the level of markers enzymes of liver cancer and preventing tumour growth. CONCLUSIONS: Alternariol methyl ether acts as a potential therapeutic target against HCC. The compound was isolated and the crystal structure was obtained for the first time from the endophytic fungus A. alternata MGTMMP031. In the present study, the crystallized structure of AME was obtained by slow evaporation technique. It can be concluded that AME acts as a potential therapeutic target against HCC. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytic fungi residing in the medicinal plants have strong biological significance and bioactive compounds from these fungi provide better therapeutic targets against diseases.

Phytosynthesis of silver nanoparticles using Mangifera indica flower extract as bioreductant and their broad-spectrum antibacterial activity.

The present study focused on the evaluation of antibacterial property of silver nanoparticles (AgNPs) synthesized using mango flower extract. The morphology of the synthesized AgNPs was observed under transmission electron microscopy and the particles have shown spherical shape in the range of 10-20 nm. X-ray powder diffraction analysis confirmed the crystalline nature of the AgNPs. The atomic percentage of the Ag element in the nanoparticles was about 7.58% which is greater than the other elements present in the sample. The AgNPs showed extensive lethal effect on both Gram-positive (Staphylococcus sp.) and Gram-negative (Klebsiella sp., Pantoea agglomerans, and Rahnella sp.) bacteria. The extensive lethal effect of AgNPs against clinically important pathogens demonstrated that the mango flower mediated AgNPs could be applied as potential antibacterial agent to control the bacterial population in the respective industries.

In-vitro bio-mineralization of arsenic and lead from aqueous solution and soil by wood rot fungus, Trichoderma sp.

In the present study, we investigated the role of calcite, i.e., microbiologically-induced precipitate by ureolytic Trichoderma sp. MG, in remediation of soils contaminated with arsenic (As) and lead (Pb). The fungus tolerates high concentrations of As (500 mg/L) and Pb (650 mg/L). The effects of three factors, i.e., urea concentration, CaCl2 concentration and pH, on urease production and bio-mineralization of As and Pb were investigated using Box-Behnken design. The maximum urease production (920 U/mL) and metal removal efficiency (68% and 59% for Pb and AS, respectively) were observed in the medium containing urea of 300 mM and CaCl2 of 75 mM at pH 9.0. Fourier transform infrared spectroscopy result revealed the formation of metal carbonates by the isolate MG. Sequential extraction of metals revealed that the carbonate fractions of As and Pb were increased to 46.4% and 42.4% in bioremediated soil, whereas in control they were 35.5% and 32.5%, respectively. The X-ray powder diffraction result further confirmed the role of calcite precipitate in bioremediation of As- and Pb-contaminated soils. The results points out that the microbiologically-induced calcite precipitation is a feasible, eco-friendly technology for the bioremediation of As- and Pb-contaminated sites.

A case of pulmonary tuberculosis masquerading as lung carcinoma.

Tuberculosis is a nimble chameleon. It can manifest itself in various ways with atypical clinical and radiographic findings. In this report we discuss the importance of radiographic findings (nodular or mass-like forms) requiring a correlation with microbiological and histopathological results to differentiate lung cancer from TB.

Structural, Mechanical, Imaging and in Vitro Evaluation of the Combined Effect of Gd3+ and Dy3+ in the ZrO2-SiO2 Binary System.

Mechanical strength and biocompatibility are considered the main prerequisites for materials in total hip replacement or joint prosthesis. Noninvasive surgical procedures are necessary to monitor the performance of a medical device in vivo after implantation. To this aim, simultaneous Gd3+ and Dy3+ additions to the ZrO2-SiO2 binary system were investigated. The results demonstrate the effective role of Gd3+ and Dy3+ to maintain the structural and mechanical stability of cubic zirconia ( c-ZrO2) up to 1400 °C, through their occupancy of ZrO2 lattice sites. A gradual tetragonal to cubic zirconia ( t-ZrO2 → c-ZrO2) phase transition is also observed that is dependent on the Gd3+ and Dy3+ content in the ZrO2-SiO2. The crystallization of either ZrSiO4 or SiO2 at elevated temperatures is delayed by the enhanced thermal energy consumed by the excess inclusion of Gd3+ and Dy3+ at c-ZrO2 lattice. The addition of Gd3+ and Dy3+ leads to an increase in the density, elastic modulus, hardness, and toughness above that of unmodified ZrO2-SiO2. The multimodal imaging contrast enhancement of the Gd3+ and Dy3+ combinations were revealed through magnetic resonance imaging and computed tomography contrast imaging tests. Biocompatibility of the Gd3+ and Dy3+ dual-doped ZrO2-SiO2 systems was verified through in vitro biological studies.

Carbon: Nitrogen (C:N) ratio level variation influences microbial community of the system and growth as well as immunity of shrimp (Litopenaeus vannamei) in biofloc based culture system.

Biofloc technology (BFT) is a novel modern aquaculture farming technique used to reduce toxic nitrogen concentration, act as in situ food source and eradicate pollutants using carbon and therefore to control C:N ratio in an aquaculture system. In this study, effect of different C:N ratios of a biofloc based system on water quality such as the level of Total ammonia nitrogen (TAN) nitrite-nitrogen (NO2--N) and nitrate nitrogen (NO3--N) were explored. Further, the growth and immunity status of shrimp L. vannamei under the influence of different C:N ratios were evaluated. Two of the C:N ratios (15 and 20) could significantly (P < 0.05) reduce TAN, NO2-N and NO3-N levels (0.456 ±â€¯0.01, 0.145 ±â€¯0.09, and 0.102 ±â€¯0.02 ppm) compared to control (1.45 ±â€¯0.1, 0.749 ±â€¯0.14 and 0.675 ±â€¯0.16 ppm). Large variations in the frequency distribution of operational taxonomic units (OTUs) for the bacterial community in water with different C:N ration (BFT) and control were observed. Vibrios often considered as opportunistic pathogens, where the most dominant bacterial flora of water in control (79%) and C:N5 (37%) group. In C:N10, Thauera (62%) was most represented genus. Similarly, Attheyaceae (56%), followed by Peridiniaceae (30%) were the most dominant groups in C:N15 treatment. The diversity of bacterial flora was more spread in C:N20 treatments with Psychrobacter (26%), Proteobacteria (25%) and Peridiniaceae (20%) as the major groups. The trend of Vibrio dominance decreased with the increase in C:N ratios and thus confirming the dominance of heterotrophic bacteria in high C:N ratio groups. Upon challenge with pathogens, shrimps from C:N10, C:N15 and C:N20 groups showed significantly higher survival (P < 0.05) compared to the C:N5 and control group. Similarly, better growth rate was also observed in BFT tanks compared to control both during the culture and at harvest. Comparatively higher expression of four immune-related genes (ras-related nuclear gene (RAN), serine proteinase gene (SP), prophenoloxidase activating enzyme (PPAE), and crustin were observed in different C:N ratio ponds than control and these were in increasing trend with the C:N ratio. Gene expression analysis showed that the transcripts of those immune genes were significantly increased among all C:N treatments than that of control. Overall, these findings demonstrated that with optimum C:N ratio, BFT can be used to optimize the bacterial community composition for both optimal water quality and optimal shrimp health. This study thus indicates the possibility of obtaining better performance of L. vannamei culture with proper adjustment of C:N ratio in a biofloc based system.

Differential Expression of MicroRNAs in Uterine Cervical Cancer and Its Implications in Carcinogenesis; An Integrative Approach.

OBJECTIVES: Cervical cancer is the second most common cancer in women in developing countries, including India. Recently, microRNAs (miRNAs) are gaining importance in cancer biology because of their involvement in various cellular processes. The present study aimed to profile miRNA expression pattern in cervical cancer, identify their target genes, and understand their role in carcinogenesis. METHODS: Human papillomavirus (HPV) infection statuses in samples were assessed by heminested polymerase chain reaction followed by direct DNA sequencing. Next-generation sequencing and miRNA microarray were used for miRNA profiling in cervical cancer cell lines and tissue samples, respectively. MicroRNA signature was validated by quantitative real-time PCR, and biological significance was elucidated using various in silico analyses. RESULTS: Cervical cancer tissues samples were mostly infected by HPV type 16 (93%). MicroRNA profiling showed that the pattern of miRNA expression differed with respect to HPV positivity in cervical cancer cell lines. However, target and pathway analyses indicated identical involvement of these significantly deregulated miRNAs in HPV-positive cervical cancer cell lines irrespective of type of HPV infected. Microarray profiling identified a set of miRNAs that are differentially deregulated in cervical cancer tissue samples which were validated using quantitative real-time PCR. In silico analyses revealed that the signature miRNAs are mainly involved in PI3K-Akt and mTOR pathways. CONCLUSIONS: The study identified that high-risk HPV induces similar carcinogenic mechanism irrespective of HPV type. The miRNA signature of cervical cancer and their target genes were also elucidated, thereby providing a better insight into the molecular mechanism underlying cervical cancer development.

Bioactive compound from Aspergillus terreusDMTMGK004 synergistically contributes towards potential anti-pathogenicity.

This study focused on the evaluation of fungal compound for their anti-pathogenic potential against respiratory pathogens. Soil samples were collected from various geographical regions in Madurai, fungal strain was isolated and identified as Aspergillus terreusDMTMGK004 (MGK004). Secondary metabolites were extracted and evaluated for antioxidant potential. It exhibited significantly high anti-proliferative property against gastric adenocarcinoma (AGS) cell lines. Antimicrobial activity against Gram positive (Streptococcus pneumoniae) and Gram negative (Klebsiella pneumoniae and Haemophilus influenzae) respiratory pathogens were analysed and the minimum inhibitory concentration (MIC) values were determined. Furthermore, the time-killing assay illustrated that the metabolite eliminates 50% of the vegetative cells within few hours of the treatment. From the spectral data, the major functional groups present in the compound were determined as carbonyl group and phenolic hydroxyl group which contribute towards its bioactivity. The compound significantly depreciates the production of extracellular polysaccharides which results in the weakening of biofilm architecture and resistance towards serum killing and phagocytosis. It also induced cell membrane damage which leads to protein and nucleic acid leakage. Hence, the results of the present study could provide a better insinuation towards the formulation of new drug targeting respiratory pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: The ubiquitous fungi Aspergillus terreus is well known for its secondary metabolite production. The fungus was evaluated for production of antagonistic molecule to reduce the growth of infectious agents causing respiratory infections. It exhibited the biological means of antioxidant, anti-proliferative and anti-pathogenic compound production. The compound exhibits killing effect against respiratory pathogens within two hours. It induced cell membrane damage leading to protein and nucleic acid leakage. It significantly reduced the production of extracellular polysaccharides. The results provide needed information to design innovative strategies for targeting pathogenic factors of the respiratory pathogens instead of killing it precisely.

Myco-phytoremediation of arsenic- and lead-contaminated soils by Helianthus annuus and wood rot fungi, Trichoderma sp. isolated from decayed wood.

In the present study, Helianthus annuus grown in arsenic- (As) and lead- (Pb) contaminated soil were treated with plant-growth promoting fungi Trichoderma sp. MG isolated from decayed wood and assessed for their phytoremediation efficiency. The isolate MG exhibited a high tolerance to As (650mg/L) and Pb (500mg/L), and could remove > 70% of metals in aqueous solution with an initial concentration of 100mg/L each. In addition, the isolate MG was screened for plant-growth-promoting factors such as siderophores, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, indole acetic acid (IAA) synthesis, and phosphate solubilisation. Phytoremediation studies indicated that treatment of H. annuus with the isolate MG had the maximum metal-accumulation in shoots (As; 67%, Pb; 59%). Furthermore, a significant increase in the soil extracellular enzyme-activities was observed in myco-phytoremediated soils. The activities of phosphatase (35 U/g dry soil), dehydrogenase (41mg TPF/g soil), cellulase (37.2mg glucose/g/2h), urease (55.4mgN/g soil/2h), amylase (49.3mg glucose/g/2h) and invertase (45.3mg glucose/g/2h) significantly increased by 12%, 14%, 12%, 22%, 19% and 14% in As contaminated soil, respectively. Similarly, the activities of phosphatase (31.4U/g dry soil), dehydrogenase (39.3mg TPF/g soil), cellulase (37.1mg glucose/g/2h), urease (49.8mgN/g soil/2h), amylase (46.3mg glucose/g/2h), and invertase (42.1mg glucose/g/2h) significantly increased by 11%, 15%, 11%, 18%, 20% and 14% in Pb contaminated soil, respectively. Obtained results indicate that the isolate MG could be a potential strain for myco-phytoremediation of As and Pb contaminated soil.

Impact of microRNA dynamics on cancer hallmarks: An oral cancer scenario.

MicroRNAs are endogenous small noncoding RNAs that negatively regulate gene expression at posttranscriptional level. The discovery of microRNAs has identified a new layer of gene regulation mechanisms, which play a pivotal role in development as well as in various cellular processes, such as proliferation, differentiation, cell growth, and cell death. Deregulated microRNA expression favors acquisition of cancer hallmark traits as well as transforms the tumor microenvironment, leading to tumor development and progression. Many recent studies have revealed altered expression of microRNAs in oral carcinoma with several microRNAs shown to have key biological role in tumorigenesis functioning either as tumor suppressors or as tumor promoters. MicroRNA expression levels correlate with clinicopathological variables and have a diagnostic and prognostic value in oral carcinoma. For these reasons, microRNA has been a hot topic in oral cancer research for the last few years. In this review, we attempt to summarize the present understanding of microRNA deregulation in oral carcinoma, their role in acquiring cancer hallmarks, and their potential diagnostic and prognostic value for oral cancer management.