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Abstract Background HPV status in a subset of HNSCC is linked with distinct treatment outcomes. Present investigation aims to elucidate the distinct clinicopathological features of HPV-positive and HPV-negative HNSCC and investigate their association with the HNSCC patient survival. Materials and methods The total RNA of exosomes from HPV-positive (93VU147T) and HPV-negative (OCT-1) HNSCC cells was isolated, and the transcripts were estimated using Illumina HiSeq X. The expression of altered transcripts and their clinical relevance were further analyzed using publicly available cancer transcriptome data from The Cancer Genome Atlas (TCGA). Results Transcriptomic analyses identified 3785 differentially exported transcripts (DETs) in HPV-positive exosomes compared to HPV-negative exosomes. DETs that regulate the protein machinery, cellular redox potential, and various neurological disorder-related pathways were over-represented in HPV-positive exosomes. TCGA database revealed the clinical relevance of altered transcripts. Among commonly exported abundant transcripts, SGK1 and MAD1L1 showed high expression, which has been correlated with poor survival in HNSCC patients. In the top 20 DETs of HPV-negative exosomes, high expression of FADS3, SGK3, and TESK2 correlated with poor survival of the HNSCC patients in the TCGA database. Conclusion Overall, our study demonstrates that HPV-positive and HPV-negative cells’ exosomes carried differential transcripts cargo that may be related to pathways associated with neurological disorders. Additionally, the altered transcripts identified have clinical relevance, correlating with patient survival in HNSCC, thereby highlighting their potential as biomarkers and as therapeutic targets.

Abstract Background Angiogenesis is an important hallmark of Glioblastoma (GBM) marked by elevated vascular endothelial growth factor-A (VEGF-A) and its receptor 2 (VEGFR-2). As previously reported nimbolide (NBL), trans-chalcone (TC) and piperine (PPR) possess promising antiangiogenic activity in several cancers however, their comparative efficacy and mechanism of antiangiogenic activity in GBM against VEGFR-2 has not been elucidated. Methods 2D and 3D spheroids cultures of U87 (Uppsala 87 Malignant Glioma) were used for evaluation of non-cytotxoic dose for anti-angiogenic activity. The antiangiogenic effect was investigated by the GBM U87 cell line bearing chick CAM model. Excised U87 xenografts were histologically examined for blood vascular density by histochemistry. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the presence of avian and human VEGF-A and VEGFR-2 mRNA transcripts. Results Using 2D and 3D spheroid models, the non-cytotoxic dose of NBL, TC and PPR was ≤ 11 µM. We found NBL, TC and PPR inhibit U87-induced neoangiogenesis in a dose-dependent manner in the CAM stand-alone model as well as in CAM U87 xenograft model. The results also indicate that these natural compounds inhibit the expression of notable angiogenic factors, VEGF-A and VEGFR-2. A positive correlation was found between blood vascular density and VEGF-A as well as VEGFR-2 transcripts. Conclusion Taken together, NBL, TC and PPR can suppress U87-induced neoangiogenesis via a reduction in VEGF-A and its receptor VEGFR-2 transcript expression at noncytotoxic concentrations. These phytochemicals showed their utility as adjuvants to GBM therapy, with Piperine demonstrating superior effectiveness among them all.

Introduction: Presumptive stressful life events scale (PSLES) is used widely in Indian life-event research. The use of PSLES in the elderly has been rather mechanistic, without giving due emphasis on the unique experiences of the elderly, particularly within the context of contemporary social change of family values in India. This research aimed to critically appraise the relevance of PSLES in the elderly. Methodology: The research was part of a larger project on stress, coping, and religiosity in (faith bases) ashram-dwelling elderly. A single consenting ashram for the elderly (for aged > 60 years) consented to the study. Participants were included if they had stayed for more than 6 months and had no impairment that compromised understanding of the research. We used the PSLES (a checklist method) for evaluating life events. We supplemented our exploration with open-ended interviews to evaluate the relevance and salience attributed to these life-events. Results: Ninety-four elderly participated (response rate was 70.15') with a mean (standard deviation) age of 74.56 (7.39) years, equally represented by either gender, with a mean duration of ashram stay of 10.85 years. Most frequent events reported were death in the family, going on a trip/pilgrimage, personal illness, and changes in biological functions. Discussion: PSLES was developed for adult Indians, and its use in the elderly may need modification due to qualitatively and quantitatively varying life events, such as the importance of nonegocentric stress (loss of job of one's child) versus egocentric stress (own hospitalization) or change of salience of events (e.g., lack of son versus daughter). Conclusion: To improve the relevance of PSLES for life-event research and capture the unique experiences of the elderly, suggested modifications are necessary.

Background: Scrub typhus, a rickettsial zoonosis, is endemic in the Indian sub-continent but is rare in the Himalayan region due to natural geographic barriers to both organism and vector. Aims: To study the clinical profile of scrub typhus cases admitted in a tertiary care center. Patients and Methods: We did a retrospective observational study of the positive cases from July 2018 to June 2019 in a tertiary care center. All possible risk factors, demographic details, clinical presentations, laboratory parameters, treatment, and outcomes were analyzed. Results: A total of 80 cases were analyzed. The maximum number of cases was observed in September. Major symptoms noted were fever, abdominal pain, headache, cough, breathlessness, and myalgia. Atypical presentations including capillary syndrome and demyelinating polyneuropathy were observed. The eschar detection rate was low. Among organ involvement, hematology system (70%) was most commonly involved followed by liver, kidney, brain, lungs, and heart respectively. The case fatality rate was 6.82%. Himalayan and non-Himalayan cohorts (n = 32 vs 48 respectively) did not show any statistically significant differences in clinical profile, although one could observe that Himalayan cohorts had higher incidences of leukopenia, splenomegaly, and myocarditis, while fever for >7days at admission, hepatomegaly, acute respiratory distress syndrome, major organ involvement resulting admission in high dependency unit (HDU), and mortality were higher in non-Himalayan cohorts. Conclusion: The current study reveals few atypical presentations and complications differing from the classical scrub typhus. Raised ALP is noticed in majority of cases which can be established as a diagnostic marker in acute undifferentiated febrile illnesses in further study. The presence of leukocytosis has high predictive association with major organ involvement and complications.

Head and neck cancer (HNC) usually arises from squamous cells of the upper aerodigestive tract that line the mucosal surface in the head and neck region. In India, HNC is common in males, and it is the sixth most common cancer globally. Conventionally, HNC attributes to the use of alcohol or chewing tobacco. Over the past four decades, portions of human papillomavirus (HPV)-positive HNC are increasing at an alarming rate. Identification based on the etiological factors and molecular signatures demonstrates that these neoplastic lesions belong to a distinct category that differs in pathological characteristics and therapeutic response. Slow development in HNC therapeutics has resulted in a low 5-year survival rate in the last two decades. Interestingly, HPV-positive HNC has shown better outcomes following conservative treatments and immunotherapies. This raises demand to have a pre-therapy assessment of HPV status to decide the treatment strategy. Moreover, there is no HPV-specific treatment for HPV-positive HNC patients. Accumulating evidence suggests that phytochemicals are promising leads against HNC and show potential as adjuvants to chemoradiotherapy in HNC. However, only a few of these phytochemicals target HPV. The aim of the present article was to collate data on various leading phytochemicals that have shown promising results in the prevention and treatment of HNC in general and HPV-driven HNC. The review explores the possibility of using these leads against HPV-positive tumors as some of the signaling pathways are common. The review also addresses various challenges in the field that prevent their use in clinical settings.