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Abstract Diverse mechanisms have been established to understand the chemoresistance of hepatocellular carcinoma (HCC), but the contribution of non-coding RNAs is not surveyed well. Here, we aimed to explore the lncRNA-miRNA axis in Hepatitis C and B virus (HCV and HBV) infected HCC to investigate the molecular mechanism of chemoresistance and to identify a potential therapeutic target for HCC. The small RNA transcriptome analysis followed by qRT-PCR validation with the liver tissues of both HCV and HBV infected HCC patients revealed that miR-424-5p, miR-136-3p, miR-139-5p, miR-223-3p, and miR-375-3p were the most downregulated miRNAs in HCC compared to normal (log2 fold change ≤−1.5, P adj ≤ 0.05). In silico pathway analysis with the validated targets of each miRNA revealed that the signalling pathway regulating pluripotency of stem cells is commonly targeted by these five miRNAs. Subsequent validation by 3′UTR-luciferase assay and western blot analysis unveiled that these five miRNAs impeded either same or diverse genes, but all linked to BMP signalling pathway such as BMPR1A/BMPR1B by miR-139-5p, miR-136-3p, and miR-375-3p, and ACVR2A/ACVR2B by miR-424-5p and miR-223-3p. Furthermore, restoration of each miRNA in Huh7/SNU449 cells inhibited phosphorylation of downstream SMAD1/5 and ERK1/2, and attenuated Epithelial-mesenchymal transition, stemness, spheroid formation, chemoresistance, invasion and migration of cells. To investigate the mechanism of suppression of these miRNAs, “DIANA” tool was employed and lncRNA-KCNQ1OT1 was retrieved as interacting partner of all the five miRNAs. In vitro RNA pull-down assay revealed that lncRNA-KCNQ1OT1 physically interacted and sequestered these five miRNAs in the cytoplasm. Hence, KCNQ1OT1 was suppressed in Huh7/SNU449 cells using CRISPR technology and observed regression of oncogenic properties with enhanced chemosensitivity and reduced metastasis in cancer cells. Shrinkage of tumour size and volume in NOD-SCID mice injected with KCNQ1OT1-sgRNA cells further strengthened our observations. Thus, lncRNA-KCNQ1OT1 is the main regulator, which reduces the level of beneficiary miRNAs in the tumour milieu and modulates BMP signalling pathway to promote chemoresistance in HCC, suggesting lncRNA-KCNQ1OT1 might have robust potential to be a therapeutic target in HCC.

Abstract Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer is more challenging and may be unresponsive to conventional therapy. Immunotherapy is crucial for treating metastatic breast cancer, but its resistance is a major limitation. The tumor microenvironment (TME) is vital in modulating the immunotherapy response. Various tumor microenvironmental components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs), are involved in TME modulation to cause immunotherapy resistance. This review highlights the role of stromal cells in modulating the breast tumor microenvironment, including the involvement of CAF-TAM interaction, alteration of tumor metabolism leading to immunotherapy failure, and other latest strategies, including high throughput genomic screening, single-cell and spatial omics techniques for identifying tumor immune genes regulating immunotherapy response. This review emphasizes the therapeutic approach to overcome breast cancer immune resistance through CAF reprogramming, modulation of TAM polarization, tumor metabolism, and genomic alterations.

Background: Local anesthetics have become vital part of multimodal analgesia approach. Instillation of local anesthetics through surgical drain is easier and safer method than conventional nerve blocks. Various local anesthetic drugs and adjuvants have been used for post-operative pain management through surgical drains. Aims and Objectives: This study was conducted to evaluate the efficacy of instillation of ropivacaine with fentanyl, dexmedetomidine or morphine through surgical drain for post-operative analgesia and patient satisfaction in patients undergoing modified radical mastectomy. Materials and Methods: A prospective, randomized, and double-blind study was conducted dividing 75 female patients aged 30–70 years who underwent modified radical mastectomy into three groups: Group (RM) received 40 ml 0.25% ropivacaine with 4.5 mg morphine, group (RD) 40 ml 0.25% ropivacaine with 1 mg/kg dexmedetomidine and group (RF) 40 ml 0.25% ropivacaine with 50 microgram fentanyl, instilled through surgical drains. Results: Visual analog score for pain at rest and movement was significantly lower in group RM as compared to group RD and RF with no significant difference among group RD and RF at different time intervals postoperatively. Patient satisfaction at 24-h postoperatively was significantly better in group RM as compared to group RD and RF (P=0.01) with no significant difference among group RD and group RF. Conclusion: Instillation of ropivacaine with morphine provides good pain relief, prolonged duration of analgesia, and good patient satisfaction in the post-operative period as compared to ropivacaine with dexmedetomidine or fentanyl.

Plastics are basically long-chain hydrocarbon compound synthesizes from nonrenewable liquid petroleum products. Since plastics have special and variety of features such as easy availability and handling, light weight, energy efficiency, nondegradable nature, cheap, faster production, and design flexibility, it has gained wide popularity in short time period and has become indispensable part of day-to-day life. The increasing usage and production of plastic with exponential rate have resulted in increasing plastic waste disposal problems which may cause adverse effect on environment and human health. Moreover, fast exhaustion of nonrenewable fossil fuel has also become a major problem. To encounter both the problem at a same time, plastic waste conversion method has come into picture. Several plastic waste conversion methods such as landfills, plastic incineration, and recycling are available out of which recycling has gained a lot of interest. One of the important recycling methods is pyrolysis, which is referred as most suitable method due to its advantages such as flexible, easy in handling, less intense sorting, less labor intensive, and high-quality liquid oil extraction. The gaseous by-product also has high calorific value. In the present study, an attempt has been made to produce alternative fuel from waste polypropylene plastic. The study further aims to compare the properties of the obtained WPPO with diesel and blend of WPPO and diesel to ascertain its feasibility for engine runs.

Abstract Background Clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein (Cas) systems are the latest addition to the plethora of gene-editing tools. These systems have been repurposed from their natural counterparts by means of both guide RNA and Cas nuclease engineering. These RNA-guided systems offer greater programmability and multiplexing capacity than previous generation gene editing tools based on zinc finger nucleases and transcription activator like effector nucleases. CRISPR-Cas systems show great promise for individualization of cancer precision medicine. Main body The biology of Cas nucleases and dead Cas based systems relevant for in vivo gene therapy applications has been discussed. The CRISPR knockout, CRISPR activation and CRISPR interference based genetic screens which offer opportunity to assess functions of thousands of genes in massively parallel assays have been also highlighted. Single and combinatorial gene knockout screens lead to identification of drug targets and synthetic lethal genetic interactions across different cancer phenotypes. There are different viral and non-viral (nanoformulation based) modalities that can carry CRISPR-Cas components to different target organs in vivo. Conclusion The latest developments in the field in terms of optimization of performance of the CRISPR-Cas elements should fuel greater application of the latter in the realm of precision medicine. Lastly, how the already available knowledge can help in furtherance of use of CRISPR based tools in personalized medicine has been discussed.

Amyotrophic lateral sclerosis (ALS) is classified as a motor neuron disease (MND) that can present with both upper and lower motor neuron signs. Concurrent ALS and frontotemporal dementia (FTD) is also a well-known phenomenon. Examples of other primary disorders mimicking ALS or ALS-FTD have been reported in the literature and recognition of these entities is important to ensure proper clinical management. We present here an unusual case of an 86-year-old male patient, clinically diagnosed with ALS and severe cognitive impairment thought to be due to FTD. Postmortem neuropathological examination of his brain and spinal cord did not reveal the typical findings of ALS or FTD. Rather, it revealed multiple non-ALS pathologies including argyrophilic grain disease (AGD), cerebrovascular disease, and Alzheimer’s type pathology. This case raises the possibility that mixed pathologies could mimic motor neuron disease.

Alzheimer’s disease (AD) is classified as a tauopathy and is the most common neuropathological correlate of dementia/cognitive impairment. AD is neuropathologically characterized by the presence of beta-amyloid immunoreactive senile plaques and tau positive neurofibrillary tangles. Neuropsychiatric symptoms of AD however continue to be underscored, and therefore, neuropathological correlates of these neuropsychiatric symptoms are not readily studied. Presented here is a case of 60-year-old female who initially presented with anxiety and depression, and continued to be the predominant symptoms although mild cognitive impairment was noted as per the available clinical notes. Postmortem examination of the brain revealed severe Alzheimer’s type neuropathological changes, which included significant tau and beta-amyloid pathology in limbic regions, which were thought to represent correlates of the patient’s depression and anxiety. This case report illustrates the possible neuropathological correlates of neuropsychiatric symptoms in patients with AD. The author hopes that such a case will promote more in-depth studies into the pathophysiology of neuropsychiatric manifestations in AD.

An in vitro study of the methanolic extract of the whole plant (except flower) of Thunbergia coccinea was performed to check the anti-oxidant activity by different methods (Reducing power assay, TBA and DPPH scavenging assay) and before starting the study, the plant was extracted by Soxhlet apparatus using methanol as solvent and the marc was evaporated kept under desiccator. From the literature survey it was found that the plant contain flavonoids and tannins which are non-enzymatic antioxidants responsible for scavenging free radicals as reported and based on this, the study for antioxidant was carried out. The methanolic extract of the plant Thunbergia coccinea shows promising result in antioxidant studies when in comparison with the standard (Ascorbic acid). Thus further studies like in vivo evaluation can be performed in the mere future.

A green synthetic protocol for cyclization of 2-aminopyridines with 2-bromoacetophenones to prepare imidazo[1,2-a]pyridines, followed by its successive iodination in one-pot manner, employing base-washed graphene oxide as the catalyst, in water has been described herewith. The current approach has offered us to carry out the reaction in water medium at room temperature and the base-washed graphene oxide catalyst has provided excellent product yield (upto 81%) and can also be recycled effortlessly upto 5 catalytic cycles, through a simple base-wash protocol. The catalyst is an inexpensive, environmentally benign, green, heterogeneous platform and has been characterised by IR, Raman, SEM and TEM studies.

CD44highCD24low population has been previously reported as cancer stem cells (CSCs) in Oral Squamous Cell Carcinoma (OSCC). Increasing evidence suggests potential involvement of microRNA (miRNA) network in modulation of CSC properties. MiRNAs have thus emerged as crucial players in tumor development and maintenance. However, their role in maintenance of OSCC stem cells remains unclear. Here we report an elevated expression of miR-146a in the CD44highCD24low population within OSCC cells and primary HNSCC tumors. Moreover, over-expression of miR-146a results in enhanced stemness phenotype by augmenting the CD44highCD24low population. We demonstrate that miR-146a stabilizes β-catenin with concomitant loss of E-cadherin and CD24. Interestingly, CD24 is identified as a novel functional target of miR-146a and ectopic expression of CD24 abrogates miR-146a driven potential CSC phenotype. Mechanistic analysis reveals that higher CD24 levels inhibit AKT phosphorylation leading to β-catenin degradation. Using stably expressing miR-146a/CD24 OSCC cell lines, we also validate that the miR-146a/CD24/AKT loop significantly alters tumorigenic ability in vivo. Furthermore, we confirmed that β-catenin trans-activates miR-146a, thereby forming a positive feedback loop contributing to stem cell maintenance. Collectively, our study demonstrates that miR-146a regulates CSCs in OSCC through CD24-AKT-β-catenin axis.

We report a case of atypical teratoid/rhabdoid tumour (AT/RT) in an adult patient in the deep grey matter with extension into the lateral ventricle. To our knowledge, this is the first example of AT/RT involving the lateral ventricle in an adult. The patient presented with headache and confusion, and subsequently required emergent surgery. His postoperative course was complicated by hemorrhage into the surgical site. The location and vascularity of the tumour affected the extent of resection achieved and likely contributed to postoperative complications. We discuss radiological features of AT/RT in adults and implications for investigations and management.

Among all other natural resources, groundwater is one of the most essential for environmental, biological, and socioeconomic activities. Several factors such as geology, distance from the river, geomorphology, slope, land-use, drainage density, lineament density, soil, and rainfall influence groundwater recharge and its availability. In this study, an integrated approach of Geographical Information System (GIS) based Multi-Criteria Decision Making (MCDM), Analytical Hierarchy Process (AHP), and remote sensing were used for geospatial mapping of groundwater. For the determination of influencing factors, an extensive literature review was considered to form a pairwise comparison matrix (PCM) and calculate the weight of each factor. The scores of the sub-parameters were also assigned based on published literature, and after that, the weighted overlay analysis (WOA) tool in ArcGIS10.1 was used to produce the final groundwater potential map. About 14% (684 km2) of the study area is recognized as ‘high groundwater potential zone’, 34% (1591 km2) in ‘moderate groundwater potential zone’, 27% (1291 km2) in ‘low groundwater potential zone’ and the remaining 24% (1141 km2) in ‘poor groundwater potential zone’. In the accuracy assessment, the groundwater potential zones i.e. high, moderate, and poor in suitability map is precisely estimated contrasting to the zone ‘low’ in the producer’s point of view, but high and poor groundwater zones detected more precisely compared to others in user’s point of view. The methodology, techniques, and results of the current investigation may be useful to evaluate the groundwater potential zone in similar drought-prone regions around the world.

Argyrophilic grain disease (AGD) is a sporadic tauopathy and actually the second most frequent cause of dementia after Alzheimer’s disease. Patients can present with slowly progressive cognitive decline as well as psychiatric manifestations such as depression. Definite diagnosis of AGD can only be made by post-mortem examination of the brain. Neuropathological features include argyrophilic grains in limbic areas along with oligodendroglial coiled bodies in hippocampal and amygdaloid white matter, and ballooned neurons in the amygdala. AGD, however, can often be overlooked and missed on neuropathologic examination as there are actually no specific clinical manifestations that would be considered highly suggestive of AGD. Thus, it is not uncommon to find neuropathological features of AGD in patients who do not present with any apparent neurological manifestations. The aim of this review is to provide an overview of what is currently known about AGD as well as raise its awareness among both neurologists and neuropathologists who may otherwise overlook this interesting tauopathy. We believe that patients above the age of 60 years should undergo post-mortem screening for AGD to avoid missed opportunity for diagnosis and enable future clinicopathological studies.

Abstract In the present days, remote sensing and geographic information system (GIS) techniques are comprehensive tools for the assessment of water resource, its management and conservation. In this study, remote sensing and GIS techniques are taken into consideration for zonation of different groundwater prospects of Pravara basin. Several contributing factors in which groundwater potential of an area entirely or partially depends such as lithology, geomorphology, slope, soil, lineament density, drainage density, land use and rainfall are assessed individually as well as together for making the different groundwater prospect maps through influencing factor (IF) and frequency ratio (FR) techniques. In ArcGIS software, all these thematic layers are prepared using different satellite imageries and conventional data sets, obtained from different sources. All these layers are transformed into high-resolution raster format and meshed together in GIS environment using IF and FR methods. Groundwater prospect maps are constructed as a result of overlay analysis. Based on the constructed map of groundwater prospect zones, as a result of this study, the study area is divided into five categories of different groundwater potential zones: very high, high, moderate, low and very low. Validation of the resultant maps has shown that frequency ratio technique is having higher accuracy (AUC = 73%) compared to the influencing factors (AUC = 69%). The present study of groundwater zonation provides a simple and less time-consuming technique; also, the results can directly be used for planning and sustainable management in Pravara basin.

Abstract Drainage network quantification with respect to the climate, tectonics, lithology and geomorphology provides significant evidence of the drainage development, hydro-geomorphic and denudation characteristics of an area. The present study was carried out by using Shuttle Radar Topographic Mission DEM to study the drainage morphometry and its influence on the hydrological characteristics of Vaitarna and Ulhas basins in Maharashtra, India. Results of the morphometric analysis reveal that the catchment of Vaitarna and Ulhas can be described as of 6th and 7th order drainage basins, encompassing an area of 3795 and 4733 km2, respectively. Additionally, Vaitarna basin is characterised by relatively higher mean bifurcation ratio as compared to the Ulhas basin, indicative of higher structural control and steeper gradient in Vaitarna basin. Lower drainage density and stream frequency affirm availability of permeable sub-surface material and homogeneous lithological characteristics in both basins. The shape parameters show both basins are semicircular with dendritic and sub-dendritic drainage pattern. The relief parameters of Vaitarna and Ulhas suggest both of these basins are characterised by very high relief and steep slope. GIS-based analysis of all these morphometric parameters indicates the drainage development of the study area progressed well beyond maturity stage and lithology have a major impact on the drainage development in Vaitarna and Ulhas basins.

Neurodegenerative diseases are a global health issue with inadequate therapeutic options and an inability to restore the damaged nervous system. With advances in technology, health scientists continue to identify new approaches to the treatment of neurodegenerative diseases. Lost or injured neurons and glial cells can lead to the development of several neurological diseases, including Parkinson’s disease, stroke, and multiple sclerosis. In recent years, neurons and glial cells have successfully been generated from stem cells in the laboratory utilizing cell culture technologies, fueling efforts to develop stem cell-based transplantation therapies for human patients. When a stem cell divides, each new cell has the potential to either remain a stem cell or differentiate into a germ cell with specialized characteristics, such as muscle cells, red blood cells, or brain cells. Although several obstacles remain before stem cells can be used for clinical applications, including some potential disadvantages that must be overcome, this cellular development represents a potential pathway through which patients may eventually achieve the ability to live more normal lives. In this review, we summarize the stem cell-based therapies that have been explored for various neurological disorders, discuss the potential advantages and drawbacks of these therapies, and examine future directions for this field.

Abstract Breast cancer is a multifactorial disease and driven by aberrant regulation of cell signaling pathways due to the acquisition of genetic and epigenetic changes. An array of growth factors and their receptors is involved in cancer development and metastasis. Receptor Tyrosine Kinases (RTKs) constitute a class of receptors that play important role in cancer progression. RTKs are cell surface receptors with specialized structural and biological features which respond to environmental cues by initiating appropriate signaling cascades in tumor cells. RTKs are known to regulate various downstream signaling pathways such as MAPK, PI3K/Akt and JAK/STAT. These pathways have a pivotal role in the regulation of cancer stemness, angiogenesis and metastasis. These pathways are also imperative for a reciprocal interaction of tumor and stromal cells. Multi-faceted role of RTKs renders them amenable to therapy in breast cancer. However, structural mutations, gene amplification and alternate pathway activation pose challenges to anti-RTK therapy.

Multiple fusiform aneurysms occurring in a single patient are very uncommon. Fusiform aneurysms affecting the anterior circulation are extremely rare and reported cases involve the middle cerebral artery and internal carotid artery. We report here a case of a 55-year-old African American male who had a history of multiple strokes and who was found unresponsive prior to his latest hospital admission. Neuroimaging was remarkable for multiple fusiform aneurysms involving segments of the anterior, middle and posterior cerebral arteries as well as subarachnoid and intraparenchymal hemorrhage. Unfortunately even after aggressive medical management, the patient did not show any signs of recovery and further management entailed comfort care measures only. The patient passed away shortly thereafter. Post-mortem examination confirmed the presence of multiple fusiform aneurysms with involvement of both the posterior and anterior circulation including the anterior cerebral artery as well as subarachnoid and intraparenchymal hemorrhage. Interestingly, there was no apparent site of aneurysm rupture identified to explain the hemorrhage. Our case is unusual in that the multiple fusiform aneurysms were found to extensively involve both the anterior and posterior circulation. Furthermore, our case demonstrates involvement of the anterior cerebral artery by fusiform aneurysms, which is also a very rare event.

Background: Atypical teratoid/rhabdoid tumor in adults is a relatively rare malignant neoplasm. It is characterized by the presence of rhabdoid cells in combination with loss of either the INI1 or BRG1protein from the tumor cells.Methods: A systematic review was conducted using MEDLINE using the terms “atypical teratoid rhabdoid tumor” AND “adult.” The systematic review was supplemented with relevant articles from the references. Cases were included if the pathology was confirmed by loss of INI1 or BRG1. We included a case from our institution. The dataset was analyzed using descriptive statistics and log-rank test.Results: A total of 50 cases from 29 articles were included in this study. The average age at diagnosis was 36.7 years. The most common locations reported are the sellar region and cerebral hemispheres (without deep gray matter involvement). Of the 50 cases, 14 were reported to show evidence of dissemination. The average overall survival was 20 months. There was a significant difference in survival between the adjuvant therapy groups (p = < 0.0001).Conclusion: Atypical teratoid rhabdoid tumor of the central nervous system in adults is a rare neoplasm associated with a poor prognosis in a majority of patients. The treatment and clinical course are highly variable, and it remains unclear which factors impact prognosis.

Sarcoidosis is a non-necrotizing granulomatous inflammatory syndrome with multisystemic manifestations. We performed a systematic review of sarcoidosis in the pediatric population with particular emphases on early onset sarcoidosis, high-risk sarcoidosis, and newly reported or unusual sarcoid-related diseases. Blau Syndrome and early onset sarcoidosis/ BS-EOS are seen in children younger than five years old presenting with extra-thoracic manifestations but usually without lymphadenopathy and/or pulmonary involvement. The prevalence of high-risk sarcoidosis is very low in children and is further limited by the difficulty of diagnosis in symptomatic children and underdiagnosis in subclinical or asymptomatic patients. Reports of sarcoidal syndromes in users of E-cigarette/marijuana/other flavorings and their induction in cancer immunotherapies are of interests and may be challenging to differentiate from metastatic malignancy. The diagnostic considerations in pediatric sarcoidosis are to support a compatible clinicoradiographic presentation and the pathologic findings of non-necrotizing granulomas by ruling out granulomas of infective etiology. There is no absolutely reliable diagnostic test for sarcoidosis at present. The use of endoscopic bronchial ultrasound (EBUS) and transbronchial fine needle aspiration (TBNA) sampling of intrathoracic lymph nodes and lung, and for superficially accessible lesions, with cytopathological assessment and pathological confirmations provide fair diagnostic yield and excellent patient safety profile in children.

Bilirubin encephalopathy/kernicterus is relatively rare, but continues to occur despite universal newborn screening. What is more interesting is the spectrum of clinical and even neuropathological findings that have been reported in the literature to be associated with bilirubin encephalopathy and kernicterus. In this review, the authors discuss the array of clinicopathological findings reported in the context of bilirubin encephalopathy and kernicterus, as well as the types of diagnostic testing used in patients suspected of having bilirubin encephalopathy or kernicterus. The authors aim to raise the awareness of these features among both pediatric neurologists and neuropathologists.

AbstractNanocomposites containing polymers, hydroxyapatite, and carbon nanotubes have shown great potential for orthopedic applications. However, the synthesis process selected significantly impacts the properties and performance of these nanocomposites. Our study described here investigated the effects of various synthesis methods on the mechanical and structural characteristics of functionalized Multi-Walled Carbon Nanotubes/Polyetheretherketone/Hydroxyapatite (f-MWCNT/PEEK/HAp) hybrid nanocomposites. Our primary objective was to comprehensively understand the many synthesis strategies that could be employed to customize these materials for orthopedic purposes. Several synthesis methods were explored by the authors to produce homogeneous nanocomposites with uniform dispersion and good interfacial bonding. Chemical solution blending, selective chemical solution blending, and three-dimensional mechanical mixing are all examples of such techniques. The produced nanocomposites were tested for crystallinity, tribological properties and molecular compositions using X-ray diffraction (XRD), tribological testing and Fourier transform infrared (FTIR) spectroscopy methods. This study demonstrated different synthesis methods for an orthopedic-targeted hybrid nanocomposite material. The hybrid nanocomposite’s formulation was changed to enhance the material’s properties. The composite was composed of polyetheretherketone (PEEK), hydroxyapatite (HAp) and functionalized multi-walled carbon nanotubes (f-MWCNT). The outstanding tribological performance of the generated nanocomposite was ensured by including the f-MWCNT and HAp in the PEEK. [ABSTRACT FROM AUTHOR]