High-throughput RNA sequencing yields novel noncoding RNAs called circular RNAs (circRNAs). They are extensively distributed across the transcriptomes of humans and other metazoans. Research has demonstrated their critical functions in multiple cellular developmental processes and diseases, including cancer, cognitive disorders, and neurodegenerative disorders (NDDs). Aside from this, circRNAs carry out cellular functions by associating with RNA-binding proteins (RBPs) that are unique for each cell type. Given that they are a vast family of proteins, RBPs regulate gene expression through various processes like stabilization, localization, splicing, nuclear export, and RNA translation. The impact of circRNAs and the RBP complex on circRNA synthesis has become more apparent in recent years. As per new findings, circRNAs interact with RBPs and modify the way in which other RNAs and proteins operate. Numerous diseases are also linked to these relationships. Because of this, research regarding the circRNA and RBP relationship is crucial to comprehend the origins of a number of disorders. This chapter describes the newly discovered mechanisms underlying the interactions between circRNAs and RBPs as well as their functional significance in both illnesses and biological processes.

Schizophrenia is a neuropsychiatric disorder characterized by various symptoms such as hallucinations, delusions, and disordered thinking. The etiology of this disease is unknown; however, it has been linked to many microdeletion syndromes that are likely to contribute to the pathology of schizophrenia. In this review we have comprehensively analyzed the role of various microdeletion syndromes, like 3q29, 15q13.3, and 22q11.2, which are known to be involved with schizophrenia. A variety of factors lead to schizophrenia phenotypes, but copy number variants that disrupt gene regulation and impair brain function and cognition are one of the causes that have been identified. Multiple case studies have shown that loss of one or more genes in the microdeletion regions lead to brain activity defects. In this article, we present a coherent paradigm that connects copy number variations (CNVs) to numerous neurological and behavioral abnormalities associated with schizophrenia. It would be helpful in understanding the different aspects of the microdeletions and how they contribute in the pathophysiology of schizophrenia.

In the past years, PDE5 has emerged as a promising therapeutic target for many cancers due to its highly upregulated expression. Interestingly, a recent in vitro study by our group has shown the antitumor and chemopotentiating action of sildenafil against T cell lymphoma. Our study showed that lower doses of sildenafil (50 μM) and cisplatin (0.5 μg/mL) exhibited 4% and 23% cytotoxicity against HuT78 cells, respectively, which was dramatically increased up to 50% when treated with both. Hence, the present study was designed to evaluate the antitumor and chemo-potentiating action of sildenafil in a murine model of T cell lymphoma (popularly called as Dalton's lymphoma [DL]). In the present study, DL-bearing mice were administered with vehicle (PBS), sildenafil (5 mg/kg bw), cisplatin (5 mg/kg bw), and sildenafil and cisplatin followed by evaluation of their impact on tumor growth by analyzing various parameters. The apoptosis was assessed by Wright-Giemsa, annexin-V, and DAPI staining. Reactive oxygen species (ROS) level was examined through DCFDA staining. The expression of genes and proteins were estimated by RT-PCR and Western blotting, respectively. The experimental findings of the study demonstrate for the first time that sildenafil inhibits tumor growth and potentiates tumor inhibitory ability of cisplatin by altering apoptosis, glycolysis, ROS homeostasis, and pH regulation in T cell lymphoma-carrying host. In addition, our investigation also showed amelioration of tumor-induced liver and kidney damage by sildenafil. Overall, the experimental data of our study strongly advocate the use and repurposing of SDF in designing promising chemotherapeutic regimens against malignancies of T cells.

Circular RNAs, abbreviated as circRNAs, are exonuclease resistant, endogenously expressed RNA, that do not code for protein, and have a circular loop like structures with covalent closure of 5′ and 3′ ends. Plentiful circRNAs are found in eukaryotes and some of them are evolutionarily conserved. They play a crucial role in diverse cellular functions like cell division, cell cycle regulation, and gene expression. Altered expression of circRNA was observed in various diseases including several cancerous conditions and neurological disorders. Glioma is basically a type of brain tumor, which originates from neuroglia cells and metastasizes to other brain tissues. Glioblastoma is the most malignant variant of this cancer with a higher mortality rate and it is less curable as compared to other cancers. Common treatments available for this disease are chemotherapy and radiotherapy. But they have side effects that they cannot differentiate between normal cells and cancerous cells. Therefore, investigating these cancerous cells at the molecular level will be a more effective way to understand glioma, owing to the specific expression patterns of proteins along with coding and non-coding RNAs. Studies found circRNAs show differential expression in glioblastoma cells and they have diverse functions at various stages and conditions of the cell. This review discusses how circRNA and protein act together and regulate the progression of glioma by directly interacting with each other or via other indirect modes of regulation. The circRNA biomarkers of glioma can be used for diagnosis purpose and interaction between circRNA and RBP play a significant role in glioma regulation and targeting these interactions may act as a possible therapeutic strategy.

Microdeletion of the 15q11.2 BP1-BP2 region, also known as Burnside–Butler susceptibility region, is associated with phenotypes like delayed developmental language abilities along with motor skill disabilities, combined with behavioral and emotional problems. The 15q11.2 microdeletion region harbors four evolutionarily conserved and non-imprinted protein-coding genes: NIPA1, NIPA2, CYFIP1, and TUBGCP5. This microdeletion is a rare copy number variation frequently associated with several pathogenic conditions in humans. The aim of this study is to investigate the RNA-binding proteins binding with the four genes present in 15q11.2 BP1-BP2 microdeletion region. The results of this study will help to better understand the molecular intricacies of the Burnside-Butler Syndrome and also the possible involvement of these interactions in the disease aetiology. Our results of enhanced crosslinking and immunoprecipitation data analysis indicate that most of the RBPs interacting with the 15q11.2 region are involved in the post-transcriptional regulation of the concerned genes. The RBPs binding to this region are found from the in silico analysis, and the interaction of RBPs like FASTKD2 and EFTUD2 with exon-intron junction sequence of CYFIP1 and TUBGCP5 has also been validated by combined EMSA and western blotting experiment. The exon-intron junction binding nature of these proteins suggests their potential involvement in splicing process. This study may help to understand the intricate relationship of RBPs with mRNAs within this region, along with their functional significance in normal development, and lack thereof, in neurodevelopmental disorders. This understanding will help in the formulation of better therapeutic approaches.

Lung cancer is the most diagnosed and the foremost cause of cancer-associated deaths worldwide. In recent few decades, noncoding RNAs (ncRNAs) are identified as a key genomic product, which tightly control the expression of various target genes involved in the regulation of various crucial cellular and pathological processes. Interestingly, the role of aberrant expression of ncRNAs has been reported in the development and progression of various cancers, including lung cancer. They are considered one of the promising biomarkers for the prognosis and diagnosis of lung cancer. Furthermore, ncRNAs are not only identified as potential predictive markers for chemo- and radioresistance in lung cancer but also have a great therapeutic value in designing novel therapeutic regimens against lung cancer. The present chapter provides detailed information regarding the role of ncRNAs in the pathogenesis of lung cancer along with their clinical applications.

Circular RNAs (CircRNAs) are a sub-class of non-coding RNA, which are covalently closed at the ends through a non-canonical process called, backsplicing from the precursor linear RNAs. These molecules are involved in several biological phenomena including regulation of gene expression, synaptic plasticity, and cognition. Several studies have shown that circRNA are present abundantly inside the mammalian brain and they are believed to be associated with the development of neurons and neuronal functions. It is also evident that alterations in intracellular and extracellular levels of circRNAs are linked with various neurological and neuropsychiatric disorders including schizophrenia (SZ). Detailed studies of circRNAs are required to decode the molecular mechanism behind the onset of SZ and the related biological activities during disease progression. This can help unravel their role in this neurobehavioral disorder and develop effective therapeutics against the disease. The present review mainly focuses on the expression and activities of the circRNAs in the post-mortem brain, peripheral blood, and exosomes. It also gives an insight into the role of circRNA interaction with RNA binding proteins (RBPs) and nucleotide modification and their therapeutic potential in the context of schizophrenia.

Transition metal dichalcogenides (TMDs) based materials have grabbed striking attention to a great extent owing to their intriguing characteristics for biological, optical, chemical and medicinal applications. Herein, we report in-situ one-pot hydrothermal-synthesis of molybdenum ditelluride@carbon nano-dots (MoTe2@C NDs) and then explored its potency in biosensing. The MoTe2@C NDs have been characterized by using X-ray Photoelectron Spectroscopy (XPS), Raman spectroscopy and Transmission Electron Microscopy (TEM) for confirmation. Furthermore, the photophysical properties of MoTe2@C NDs have been examined. Under radiation of Ultra-Violet (UV) light (lambda = 365 nm), the MoTe2@C NDs emit cyan fluorescence which has been confirmed by photoluminescence (PL) spectroscopy (PL peak at similar to 431 nm, excitation wavelength similar to 350 nm). The as-synthesized sample has been subjugated for the sensing of hydrogen-peroxide (H2O2) molecules. Notably, with a gradual proliferation of the concentration of H2O2, the PL intensity of the MoTe2@C NDs decreases and is found to be linear (R-2 = 0.9986). The detection-limit has also been estimated as 14.22 nM. The PL quenching-mechanism has been elucidated based on three-level kinetic model considering charge separated-trap states ((1)[D+center dot center dot center dot A(-)] <-> (3)[D+center dot center dot center dot A(-)]). This is the first work of hydrothermal-synthesis of MoTe2@C NDs and study of its optical properties, which has efficient potential to use as H2O2 sensor in industrial/biomedical applications.

OBJECTIVE:This study aimed to evaluate the epidemiological and clinicopathological spectrum of ocular malignancies among patients presenting to a teaching hospital in Northern India.METHODS:A total of 246 histopathologically diagnosed patients with ocular malignancies were included in the study. Tumor type and size, primary origin and location of tumor, clinical staging, radiological findings, histopathological type, and treatment outcomes were assessed.RESULTS:Overall, males over 55 years of age were most commonly affected and the majority of cases were primary ocular or adnexal malignancies (n = 226; 91.87%). The eyelids and periocular structures (n = 92; 37.40%) were the most commonly involved site, followed by the orbit (n = 72; 29.27%), ocular surface (n = 46; 18.70%) and intraocular region (n = 36; 14.63%). The majority of the patients (n = 68; 27.64%) were managed by primary surgical excision and reconstruction. However, 46 patients (18.70%) with advanced lesions underwent neoadjuvant chemotherapy followed by surgical excision and more extensive orbital lesions were treated by exenteration followed by adjuvant chemotherapy (n=48; 19.51%), while patients with metastatic tumor were given palliative chemotherapy/external beam radiation therapy (n= 46; 18.70%). Overall, 45.12% of patients were cured completely, 15.45% showed a partial response to the treatment, 13.04% had progressive disease and 16.67% demonstrated disease recurrence.CONCLUSION:A clinicopathological analysis of ocular malignancies at a teaching hospital in Northern India indicated the preponderance of primary ocular malignancies, with eyelid sebaceous gland carcinomas being the most common pathological diagnosis. Most of our patients had advanced and extensive disease among them majority belonged to the rural background and poor socio-economic status.

Nimbolide is a tetranortriterpenoid derived from the leaves and flowers of Azadirachta indica (Neem). It exhibits anticancer activity against a variety of cancers by modulating various crucial features, including cell proliferation, apoptosis, and invasion and metastasis. More importantly, the cytotoxic effect of nimbolide has also been observed against T cell lymphoma, but the underlying mechanisms are still unexplored. So far, no study has been conducted to observe the effect of nimbolide on cancer cell metabolism. Therefore, the present investigation was designed to explore the molecular mechanisms of the antitumor potential of nimbolide against T cell lymphoma, a neoplastic disorder of thymic origin. In addition, we also unraveled the anti‐glycolytic activity of nimbolide against T lymphoma cells with possible molecular mechanisms. Our results showed the cytotoxic action of nimbolide against three different cell lines of T cell lymphoma, namely Dalton's lymphoma, HuT‐78, and J6. Nimbolide‐induced apoptosis in T lymphoma cells by altering the level of reactive oxygen species, p53, Bcl2, Bax, and cytochrome c, with subsequent cleavage of caspase 3. Remarkably, nimbolide inhibited the expression of hypoxia‐inducible factor‐1α, glucose transporter 3, hexokinase II, and pyruvate dehydrogenase kinase 1, which led to the suppression of glycolysis with concomitant activation of oxidative phosphorylation. Hence, the results of the present investigation demonstrate that nimbolide exerts tumoricidal activity against T lymphoma cells via augmentation of apoptosis and reversal of altered cell metabolism. Thus, the present study provides a new insight for the therapeutic utilization of nimbolide against T cell lymphoma.

Level lifetimes in 106Pd were measured with the Doppler-shift attenuation method following inelastic neutron scattering, and electric monopole transition strengths between low-lying 2+ states were deduced. The large \( \rho^{2}\)(E0) values obtained provide evidence for shape coexistence, extending observation of such structures in the N = 60 isotones. Included in these results is the first determination of the E0 transition strength in the Pd nuclei between levels with K = 2 .

Culturable methanotrophic bacteria (CMB) were studied in the soils of forest and savanna of tropical dry deciduous forest ecosystems employing most probable number (MPN) technique. The spatiotemporal study was conducted at the six sites differing in the soil physicochemical properties and vegetational cover. CMB population was high in the moist sites compared to the dry sites and in sub soil below 10 cm depth. The top soil population ranged between 7.0 × 10 4 to 7.1 × 10 6 g -1 dry soil. The population declined exponentially with depth. In temporal study at bimonthly interval for two consecutive years, high CMB population was in winter that declined 10 20 fold in rain. The CMB population variation was explained solely by temperature (59%), temperature and soil nitrate (76%), and temperature soil nitrate and moisture (77.4%) in the step wise regression analysis. Index Terms Dry tropical forest, Methanotrophs; MOB, NH4 + -N; NO3 -N; Soil moisture; spatiotemporal variation, ————————————————————