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35 result(s) for "Pathania, B."
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miR‐15a‐5p, miR‐15b‐5p, and miR‐16‐5p inhibit tumor progression by directly targeting MYCN in neuroblastoma
Neuroblastoma (NB) is the most common extracranial solid malignancy in children. Despite current aggressive treatment regimens, the prognosis for high‐risk NB patients remains poor, with the survival of less than 40%. Amplification/stabilization of MYCN oncogene, in NB is associated with a high risk of recurrence. Thus, there is an urgent need for novel therapeutics. The deregulated expression of microRNA (miR) is reported in NB; nonetheless, its effect on MYCN regulation is poorly understood. First, we identified that miR‐15a‐5p, miR‐15b‐5p, and miR‐16‐5p (hereafter miR‐15a, miR‐15b or miR‐16) were down‐regulated in patient‐derived xenografts (PDX) with high MYCN expression. MiR targeting sequences on MYCN mRNA were predicted using online databases such as TargetScan and miR database. The R2 database, containing 105 NB patients, showed an inverse correlation between MYCN mRNA and deleted in lymphocytic leukemia (DLEU) 2, a host gene of miR‐15. Moreover, overexpression of miR‐15a, miR‐15b or miR‐16 significantly reduced the levels of MYCN mRNA and N‐Myc protein. Conversely, inhibiting miR dramatically enhanced MYCN mRNA and N‐Myc protein levels, as well as increasing mRNA half‐life in NB cells. By performing immunoprecipitation assays of argonaute‐2 (Ago2), a core component of the RNA‐induced silencing complex, we showed that miR‐15a, miR‐15b and miR‐16 interact with MYCN mRNA. Luciferase reporter assays showed that miR‐15a, miR‐15b and miR‐16 bind with 3’UTR of MYCN mRNA, resulting in MYCN suppression. Moreover, induced expression of miR‐15a, miR‐15b and miR‐16 significantly reduced the proliferation, migration, and invasion of NB cells. Finally, transplanting miR‐15a‐, miR‐15b‐ and miR‐16‐expressing NB cells into NSG mice repressed tumor formation and MYCN expression. These data suggest that miR‐15a, miR‐15b and miR‐16 exert a tumor‐suppressive function in NB by targeting MYCN. Therefore, these miRs could be considered as potential targets for NB treatment. A model summarizing how miR‐15a, miR‐15b, and miR‐16 suppress tumor progression in neuroblastoma by targeting MYCN. When miRs are overexpressed, argonaute‐2‐mediated interaction of miR with MYCN mRNA increases, followed by degradation of MYCN, leading to neuroblastoma regression.
Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial
Several phase II studies have demonstrated that psilocybin-assisted therapy shows therapeutic potential across a spectrum of neuropsychiatric conditions, including major depressive disorder (MDD). However, the mechanisms underlying its often persisting beneficial effects remain unclear. Observational research suggests that improvements in psychological flexibility may mediate therapeutic effects. However, no psychedelic trials to date have substantiated this finding in a clinical sample. In an exploratory placebo-controlled, within-subject, fixed-order study, individuals with moderate to severe MDD were administered placebo (n = 19) followed by psilocybin (0.3 mg/kg) (n = 15) 4 weeks later. Dosing sessions were embedded within a manualized psychotherapy that incorporated principles of Acceptance and Commitment Therapy. Depression severity, psychological flexibility, mindfulness, and values-congruent living were measured over a 16-weeks study period. Psychological flexibility, several facets of mindfulness, and values-congruent living significantly improved following psilocybin and were maintained through week 16. Additionally, improvements in psychological flexibility and experiential acceptance were strongly associated with reductions in depression severity following psilocybin. These findings support the theoretical premise of integrating psilocybin treatment with psychotherapeutic platforms that target psychological flexibility and add to emerging evidence that increasing psychological flexibility may be an important putative mechanism of change in psilocybin-assisted therapy for MDD and potentially, other mental health conditions.
COVID-19 and Cancer Comorbidity: Therapeutic Opportunities and Challenges
The coronavirus disease 2019 (COVID-19) is a viral disease caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that affects the respiratory system of infected individuals. COVID-19 spreads between humans through respiratory droplets produced when an infected person coughs or sneezes. The COVID-19 outbreak originated in Wuhan, China at the end of 2019. As of 29 Sept 2020, over 235 countries, areas or territories across the globe reported a total of 33,441,919 confirmed cases, and 1,003,497 confirmed deaths due to COVID-19. Individuals of all ages are at risk for infection, but in most cases disease severity is associated with age and pre-existing diseases that compromise immunity, like cancer. Numerous reports suggest that people with cancer can be at higher risk of severe illness and related deaths from COVID-19. Therefore, managing cancer care under this pandemic is challenging and requires a collaborative multidisciplinary approach for optimal care of cancer patients in hospital settings. In this comprehensive review, we discuss the impact of the COVID-19 pandemic on cancer patients, their care, and treatment. Further, this review covers the SARS-CoV-2 pandemic, genome characterization, COVID-19 pathophysiology, and associated signaling pathways in cancer, and the choice of anticancer agents as repurposed drugs for treating COVID-19.
The miR-29 family facilitates the activation of NK-cell immune responses by targeting the B7-H3 immune checkpoint in neuroblastoma
Neuroblastoma (NB) is a highly aggressive pediatric cancer that originates from immature nerve cells, presenting significant treatment challenges due to therapy resistance. Despite intensive treatment, approximately 50% of high-risk NB cases exhibit therapy resistance or experience relapse, resulting in poor outcomes often associated with tumor immune evasion. B7-H3 is an immune checkpoint protein known to inhibit immune responses. MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation. Our study aims to explore the impact of miRNAs on B7-H3 regulation, the anti-tumor immune response, and tumorigenicity in NB. Analysis of NB patients and patient-derived xenograft tumors revealed a correlation between higher B7-H3 expression and poorer patient survival. Notably, deceased patients exhibited a depletion of miR-29 family members (miR-29a, miR-29b, and miR-29c), which displayed an inverse association with B7-H3 expression in NB patients. Overexpression and knockdown experiments demonstrated that these miRNAs degrade B7-H3 mRNA, resulting in enhanced NK cell activation and cytotoxicity. In vivo, experiments provided further evidence that miR-29 family members reduce tumorigenicity, macrophage infiltration, and microvessel density, promote infiltration and activation of NK cells, and induce tumor cell apoptosis. These findings offer a rationale for developing more effective combination treatments that leverage miRNAs to target B7-H3 in NB patients.
Comparative analysis the complete chloroplast genomes in wild Musa species of India for its phylogenetic and taxonomic implications
Background The genus Musa , belonging to the family Musaceae, includes important horticultural and food crops such as bananas and plantains. In this study, we sequenced and analyzed the complete chloroplast genomes of four wild Indian Musa taxa: M. balbisiana var. andamanica , M. indandamanensis , M. paramjitiana , and M. sikkimensis , for ascertaining their taxonomic status and phylogenetic relationship. Results The chloroplast genomes ranged from 169,485 bp to 169,861 bp in length and exhibited a typical quadripartite structure with a pair of inverted repeat regions separated by a large single copy and a small single copy region. The genomes encoded 113 unique genes, including 79 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. Comparative analyses revealed a relatively conserved genome structure, with coding regions being less variable than noncoding regions. Eleven divergent hotspots were identified that could serve as potential molecular markers for species identification and phylogenetic studies. Codon usage analysis revealed a preference for A/T-ending codons, and most protein-coding genes were under purifying selection. Phylogenetic analyses based on the complete chloroplast genomes and various regions (LSC, SSC, IR, and CDS) supported the conspecific status of M. paramjitiana and M. balbisiana var. andamanica with M. balbisiana . Conclusions The results provide valuable insights into the evolutionary relationships and taxonomic classification of wild Musa species and highlight the potential of chloroplast genomes as tools for species identification and phylogenetic studies in the genus Musa .
Efficacy of 20 min yoga module for reducing burnout among healthcare workers: protocol of randomised control trial and results of pilot study
Burnout among healthcare workers is a significant global concern that affects their well-being and professional efficacy. Yoga has shown promise in reducing burnout and improving mental health outcomes. However, due to their hectic schedules, healthcare workers often struggle to find time for self-care. A 20 min yoga module has been developed specifically for them to address this. So, this study aims to assess the efficacy of a specific 20 min yoga module in reducing burnout among healthcare workers. An open-label, two-arm, randomised controlled trial involving healthcare workers aged 20–35 years participating for 4 weeks. Exclusion criteria included recent illness, respiratory ailments, pregnancy, life-threatening medical conditions or physical inability to perform yoga. After randomisation of 108 participants, they will be equally allocated to either the yoga group (20 min yoga) or the control group (20 min medium-paced walking). The primary outcome will be burnout, whereas the secondary outcomes include stress, anxiety, selective attention and happiness. Data collection: at baseline and after 4 weeks of intervention, compliance is monitored via daily attendance records. Descriptive and inferential analyses will employ intention-to-treat and per-protocol analysis using SPSS 26.0. A study with 20 participants found that a 20 min yoga intervention significantly improved emotional exhaustion, depersonalisation, personal accomplishment, happiness and Spielberger’s State-Trait Anxiety/Six-letter cancellation test scores. Cortisol levels showed trends of reduction but were not significant. These results inform the upcoming main trial. Ethical approval is obtained from the Institutional Ethical Committee via letter number AIIMS/IEC/20/762. The trial findings will be shared through peer-reviewed publications and presentations at conferences. Trial registration number: CTRI/2021/01/030568; Clinical Trial Registry of India.
Etomidate-ketamine versus dexmedetomidine-ketamine for entropy-guided procedural sedation during endoscopic retrograde cholangiopancreatography procedures: A randomized single blind study
  Background and Aims The major challenge for the anesthetist in endoscopic retrograde cholangiopancreatography (ERCP) procedures is to provide moderate to deep levels of sedation in prone position with preservation of spontaneous respiratory efforts in shared airway scenario with an endoscopist. These patients have other comorbidities, making them vulnerable to complications during the routinely used sedation with propofol. We compared the entropy-guided efficacy of combination of etomidate-ketamine to dexmedetomidine-ketamine in patients undergoing ERCP. Methods This prospective single blind randomized entropy-guided trial was conducted on 60 patients with etomidate-ketamine in group I ( n  = 30) and dexmedetomidine-ketamine in group II ( n  = 30). The purpose was to compare etomidate-ketamine versus dexmedetomidine-ketamine for ERCP in terms of intraprocedural hemodynamics with desaturation, onset of sedation, recovery time and endoscopist’s satisfaction. Results Hypotension was observed only in six (20%) patients of group II ( p  < 0.009). Two patients of group I and three in group II desaturated (Spo2 < 90) briefly during the procedure, but none of the patient required intubation ( p  > 0.05). The mean time in minutes of onset of sedation was 1.15 in group I and 5.6 in group II ( p  < 0.001). Endoscopists’ satisfaction was better in group I ( p  ≤ 0.001) and length of recovery room stay was shorter in group I as compared to that in group II ( p  ≤ 0.007). Conclusion We conclude that entropy-guided intravenous procedural sedation with etomidate-ketamine combination provides faster onset of sedation, stable periprocedural hemodynamics, rapid recovery and fair to excellent endoscopist satisfaction compared to dexmedetomidine-ketamine combination for ERCP.