Right dorsolateral pre-frontal high-frequency rTMS was found to have significant anticraving effects in alcohol dependence. The results highlight the potential of rTMS which, combined with other anticraving drugs, can act as an effective strategy in reducing craving and subsequent relapse in alcohol dependence.

P‐element induced wimpy testis (PIWI)‐interacting RNAs (piRNAs) are a promising class of small regulatory RNAs, earlier believed to control transposable elements (TEs) activity in germlines are now reported in somatic and cancer cells. The aberrant expression of piRNAs has been documented in various cancers wherein they modulate tumorigenesis either as oncogenes or tumor suppressors by curbing target gene expression. However, there is no report yet on the association of piRNAs in fibrosarcoma, an early metastatic lethal tumor. For the first time, we reported a piRNA, piR‐39980 in fibrosarcoma and investigated its potential role in malignancy by employing several methods such as qRT‐PCR, MTT assay, transwell invasion and migration assay, wound healing assay, flow cytometric cell cycle analysis, Annexin V‐PE apoptosis assay, AO/EB dual staining assay, and chromatin condensation assay. We observed that piR‐39980 significantly attenuated proliferation, migration, invasion, and colony forming ability as well as induced apoptotic cell death of HT1080 fibrosarcoma cells when transiently overexpressed with its piRNA mimics. The dual luciferase reporter assay confirmed that piR‐39980 promotes apoptosis and inhibits proliferation in fibrosarcoma by repressing RRM2 through direct targeting at its 3′UTR through extensive sequence complementary binding, unlike microRNA targeting. In summary, this study revealed that piR‐39980 has a strong anti‐tumor effect and hence could be a promising RNA‐based therapeutic agent for the malignancy of fibrosarcoma.

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The abnormal expressions of microRNAs (miRNAs) are known to be associated with various pathophysiological processes that lead to the development of a plethora of diseases including cancer. Among several miRNAs studied so far, miR-197 has been reported to play a vital role either as an oncogene or tumor suppressor in different cancers. However, its role in carcinogenesis of fibrosarcoma has not yet been elucidated. Therefore, the current study investigated the role of miR-197-5p, which is significantly downregulated in HT1080 fibrosarcoma cells compared to IMR90-tert fibroblast cells. The transient overexpression of miR-197-5p causes a significant decrease in viability and proliferation of fibrosarcoma cells in both concentration-and time-dependent manners. Interestingly, we did not observe any significant changes in cell cycle pattern or apoptotic cell populations, but rather noticed cellular senescence of fibrosarcoma cells upon overexpression of miR-197-5p. Further, this miRNA suppresses the metastatic properties, such as migration, invasion, and anchorageindependent growth of fibrosarcoma possibly through targeting KIAA0101, which is a proliferating cell nuclear antigen-associated factor and overexpressed in the malignancy. In nutshell, our result revealed that miR-197-5p acts as an oncosuppressor miRNA in fibrosarcoma through target regulation of KIAA0101, which can be exploited for developing RNA-based therapeutic strategies for the cure of this malignancy.

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Neuroblastoma (NB) is the leading pediatric cancer known for its heterogeneity and clinical aggressiveness leading to chemoresistance. Recent evidence in small RNA research has led to the discovery of PIWI-interacting RNAs (piRNAs) which work in an orchestrated fashion to modulate gene expression both in homeostatic conditions and abnormalities like cancer including NB. This study aims to decipher the possible role of a repeat-derived piRNA, piR-39980 (identified from our previous piRNA profiling study in human NB cell lines) in tumorigenesis of NB cells. piR-39980, overexpressed in NB cells act as an oncopiR and promotes tumor progression, while its inhibition resulted in reduced viability, invasion as well as the migration of IMR-32 cells. Interestingly, we observed that inhibition of piRNA induces senescence of NB cells without affecting the classical apoptosis pathway by modulating the expression of JAK3 through target binding. In addition, piR-39980 was found to desensitize the effect of doxorubicin and inhibit drug-induced apoptosis. Overall, we report piR-39980, as the first oncopiR which might serve as a novel therapeutic target for this malignancy.

ObjectiveSchneiderian first-rank symptoms (FRS) and abnormal EEG gamma activity in schizophrenia have been reported independently to have a neurodevelopmental basis. We aimed to investigate spontaneous gamma power in two groups of first episode schizophrenia patients (those who experience FRS and those who do not).MethodsA comparative hospital based study having 37neuroleptic naïve male patients with schizophrenia divided into two groups-FRS(+) and FRS(-) groups based on the presence of FRS. Thirty age, sex, education and handedness matched individuals served as controls (N). All participants underwent a 192-channel resting Electroencephalography (EEG) recording. Gamma spectral power was calculated for low- (30-50 Hz) and high-gamma 1 & 2 (51-70 and 71-100 Hz) bands. Spectral power was compared between three groups using MANOVA and supplementary one-way ANOVA with Bonferroni test controlling for multiple comparisons. Linear regression was used to identifying predictor variables for FRS. Pearson correlation coefficient was computed between spectral power parameters and various clinical variables.ResultsSignificantly higher high gamma band-1 power was observed over right frontal (p<0.05), parietal (p<0.05) and temporal (p<0.05) regions in FRS(+) than FRS(-) group and normal controls. Right parietal high gamma-1 power and paranoid cluster on PANSS significantly predicted number of FRS in total schizophrenia patients; paranoid cluster on PANSS showed significant correlation with number of FRS in FRS(+) group.ConclusionFindings of our study add to the evidence that areas contained within the hetero modal association cortex are associated with FRS. The study findings also strengthen the neurodevelopmental basis of FRS in schizophrenia.

Resistance to doxorubicin (DOX) is an obstacle to successful sarcoma treatment and a cause of tumor relapse, with the underlying molecular mechanism still unknown. PIWI-interacting RNAs (piRNAs) have been shown to enhance patient outcomes in cancers. However, there are few or no reports on piRNAs affecting chemotherapy in cancers, including fibrosarcoma. The current study aims to investigate the relationship between piR-39980 and DOX resistance and the underlying mechanisms. We reveal that piR-39980 is less expressed in DOX-resistant HT1080 (HT1080/DOX) fibrosarcoma cells. Our results show that inhibition of piR-39980 in parental HT1080 cells induces DOX resistance by attenuating intracellular DOX accumulation, DOX-induced apoptosis, and anti-proliferative effects. Its overexpression in HT1080/DOX cells, on the other hand, increases DOX sensitivity by promoting intracellular DOX accumulation, DNA damage, and apoptosis. The dual-luciferase reporter assay indicates that piR-39980 negatively regulates RRM2 and CYP1A2 via direct binding to their 3′UTRs. Furthermore, overexpressing RRM2 induces DOX resistance of HT1080 cells by rescuing DOX-induced DNA damage by promoting DNA repair, whereas CYP1A2 confers resistance by decreasing intracellular DOX accumulation, which piR-39980 restores. This study reveals that piR-39980 could reduce fibrosarcoma resistance to DOX by modulating RRM2 and CYP1A2, implying that piRNA can be used in combination with DOX.