Prevalence of internet addiction among college students in the Indian setting: a systematic review and meta-analysis

BackgroundThe internet is an integral part of everyone’s life. College going adolescents are highly vulnerable to the misuse of the internet.AimsTo estimate the pooled prevalence of internet addiction (IA) among college students in India.MethodsLiterature databases (PubMed, Web of Science, Scopus, EMBASE, PsycINFO and Google Scholar) were searched for studies assessing IA using the Young Internet Addiction Test (Y-IAT) among adolescents from India, published in the English language up to December 2020. We included studies from 2010 to 2020 as this is the marked era of momentum in wireless internet connectivity in India. The methodological quality of each study was scored, and data were extracted from the published reports. Pooled prevalence was estimated using the fixed-effects model. Publication bias was evaluated using Egger’s test and visual inspection of the symmetry in funnel plots.ResultsFifty studies conducted in 19 states of India estimated the prevalence of IA and the overall prevalence of IA as 19.9% (95% CI: 19.3% to 20.5%) and 40.7% (95% CI: 38.7% to 42.8%) based on the Y-IAT cut-off scores of 50 and 40, respectively. The estimated prevalence of severe IA was significantly higher in the Y-IAT cut-off points of 70 than 80 (12.7% (95% CI: 11.2% to 14.3%) vs 4.6% (95% CI: 4.1% to 5.2%)). The sampling method and quality of included studies had a significant effect on the estimation of prevalence in which studies using non-probability sampling and low risk of bias (total quality score ≥7) reported lower prevalence. The overall quality of evidence was rated as ‘moderate’ based on the Grading of Recommendations Assessment, Development and Evaluation criteria.ConclusionsOur nationally representative data suggest that about 20% to 40% of college students in India are at risk for IA. There is a need for further research in the reconsideration of Y-IAT cut-off points among Indian college students.PROSPERO registration numberCRD42020219511.     

In vitro anti inflammatory activity of Aloe vera by down regulation of MMP-9 in peripheral blood mononuclear cells

Aim of the study

The anti-inflammatory activity of Aloe vera was investigated through MMP inhibition studies. The effect of Aloe vera on MMP-9 inhibition was tested on peripheral blood mononuclear cells (PBMC).

Materials and methods

Peripheral blood mononuclear cells (PBMC) were isolated from the heparinised venous blood by Ficoll Diatrizoate gradient centrifugation. The cell count and viability was determined using dye exclusion technique. Cytotoxicity was evaluated by MTT assay. Activation of MMP-9 was visualized by gelatin zymography. Inhibition of MMP-9 in the presence of aqueous extract of Aloe vera was detected by gelatin zymography and confirmed by RT-PCR.

Results

Peripheral blood mononuclear cells (PBMC) showed significant inhibition in the activity of MMP-9, indicating the in vitro inhibitory effect of Aloe vera on MMP-9. Zymographic analysis and RT-PCR showed that it caused a significant reduction in the production of MMP-9 in a concentration dependent manner.

Conclusion

The inhibition of MMP-9 production in the cells was detected by gelatin zymography and was confirmed by RT-PCR.     

Role of astrocytes in reproduction and neuroprotection

Hypothalamic astrocytes secrete TGF-beta and 3 alpha,5 alpha-tetrahydro progesterone (3 alpha,5 alpha-THP) in culture. When the astrocyte-conditioned medium (ACM) was incubated with the hypothalamic cell line GT1-7, it resulted in the secretion of GnRH. Immunoneutralization with TGF-beta antibody or ultra-filteration with a 10 kDa cut off filter resulted in attenuation of the GnRH releasing ability of ACM, indicating that TGF-beta was a major factor involved with GnRH release. Treatment with estrogens increases TGF-beta secretion. These observations indicate a significant role of astrocytes in GnRH secretion. Serum-deprivation results in the death of GT1-7 neurons in culture and addition of ACM or TGF-beta to the culture, attenuates cell death. The mechanism of protection from cell death appears to involve phosphorylation of MKK4, JNK, c-Jun(Ser63), and enhancement of AP-1 binding. Co-administration of JNK inhibitors, but not MEK inhibitors attenuated ACM or TGF-beta-induced c-Jun(Ser63) phosphorylation and their neuroprotective effects. These studies suggest that astrocytes can protect neurons, at least in part, by the release of TGF-beta and activation of a c-Jun/AP-1 protective pathway.     

Enhanced ubiquitination of cytoskeletal proteins in pressure overloaded myocardium is accompanied by changes in specific E3 ligases

Ubiquitin conjugation of proteins is critical for cell homeostasis and contributes to both cell survival and death. Here we studied ubiquitination of proteins in pressure overloaded (PO) myocardium in the context of cardiomyocyte survival. Analysis using a feline right ventricular pressure overload (RVPO) model revealed a robust and transient increase in ubiquitination of proteins present in the Triton X-100-insoluble fraction in 24 to 48 h PO myocardium, and confocal micrographs indicate this increase in ubiquitination occurs subsarcolemmaly near the intercalated disc area of cardiomyocytes. The ubiquitination was accompanied by changes in E3 ligases including Cbl, E6AP, Mdm2 and cIAP in the same period of PO, although atrophy-related E3 ligases, MuRF1 and MuRF3 were unaltered. Furthermore, Cbl displayed a substantial increase in both levels of expression and tyrosine phosphorylation in 48 h PO myocardium. Confocal studies revealed enrichment of Cbl at the intercalated discs of 48 h PO cardiomyocytes, as evidenced by its colocalization with N-cadherin. Although apoptosis was observed in 48 h PO myocardium by TUNEL staining, cardiomyocytes showing ubiquitin staining were not positive for TUNEL staining. Furthermore, 48 h PO resulted in the phosphorylation of inhibitor of nuclear factor kappa B (IkappaB), suggesting its ubiquitin-mediated degradation and the nuclear localization of NFkappaB for the expression of specific cell survival factors such as cIAPs. Together these data indicate that increased levels of E3 ligases that regulate cell homeostasis and promote cell survival could ubiquitinate multiple cytoskeletal protein targets and that these events that occur during the early phase of PO may contribute to both cardiomyocyte survival and hypertrophy.     

Erythropoietin prevents haloperidol treatment-induced neuronal apoptosis through regulation of BDNF.

Functional alterations in the neurotrophin, brain-derived neurotrophic factor (BDNF) have recently been implicated in the pathophysiology of schizophrenia. Furthermore, animal studies have indicated that several antipsychotic drugs have time-dependent (and differential) effects on BDNF levels in the brain. For example, our previous studies in rats indicated that chronic treatment with the conventional antipsychotic, haloperidol, was associated with decreases in BDNF (and other neurotrophins) in the brain as well as deficits in cognitive function (an especially important consideration for the therapeutics of schizophrenia). Additional studies indicate that haloperidol has other deleterious effects on the brain (eg increased apoptosis). Despite such limitations, haloperidol remains one of the more commonly prescribed antipsychotic agents worldwide due to its efficacy for the positive symptoms of schizophrenia and its low cost. Interestingly, the hematopoietic hormone, erythropoietin, in its recombinant human form rhEPO has been reported to increase the expression of BDNF in neuronal tissues and to have neuroprotective effects. Such observations provided the impetus for us to investigate in the present study whether co-treatment of rhEPO with haloperidol could sustain the normal levels of BDNF in vivo in rats and in vitro in cortical neuronal cultures and further, whether BDNF could prevent haloperidol-induced apoptosis through the regulation of key apoptotic/antiapoptotic markers. The results indicated that rhEPO prevented the haloperidol-induced reduction in BDNF in both in vivo and in vitro experimental conditions. The sustained levels of BDNF in rats with rhEPO prevented the haloperidol-induced increase in caspase-3 (p<0.05) and decrease in Bcl-xl (p<0.01) protein levels. Similarly, in vitro experiments showed that rhEPO prevented (p<0.001) the haloperidol-induced neuronal cell death as well as the decrease in Bcl-xl levels (p<0.01). These findings may have significant implications for the development of neuroprotective strategies to improve clinical outcomes when antipsychotic drugs are used chronically.     

Dendritic cells primed with HPV positive cervical tumor lysate are superior to unprimed DCs in migratory capacity and induce a potent Th1 response

In this study, we assessed the efficacy of tumor lysate primed and unprimed monocyte derived mature dendritic cells (DCs) to trigger an effective anti-tumor immune response in cervical cancer patients who tested positive for human papilloma virus (HPV) DNA. Lysate primed and unprimed DCs were assessed for the expression of CD80, CD86, CD40, HLADR and CD83. The ability of DCs to migrate in response to the chemokines CCL19 and 21 as well as their ability to secrete IL12p40 was investigated. Mixed lymphocyte proliferation assays were used to assess DC stimulatory capacity and their ability to generate a Th1 response. Our results showed no difference in phenotypic expression between primed and unprimed DCs but both had significantly increased expression of the activation marker CD83 when compared to immature DCs. Importantly, the primed DCs showed significant (P value = 0.03) IL-12p40 secretion and a superior migratory capacity towards CC19 and CCL21 (P value = 0.04) compared to unprimed DCs even after cytokine withdrawal. Primed DCs showed superior stimulation of T cell proliferation (allogeneic and autologous) and secretion of IFN gamma (IFN-γ) than the unprimed DCs. Hence whole tumor lysate primed mature DCs could be potent immunotherapeutic adjuvants to standard treatment for cervical cancer.     

High mobility group box protein‐1 promotes cerebral edema after traumatic brain injury via activation of toll‐like receptor 4

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Cerebral edema, a life‐threatening medical complication, contributes to elevated intracranial pressure (ICP) and a poor clinical prognosis after TBI. Unfortunately, treatment options to reduce post‐traumatic edema remain suboptimal, due in part, to a dearth of viable therapeutic targets. Herein, we tested the hypothesis that cerebral innate immune responses contribute to edema development after TBI. Our results demonstrate that high‐mobility group box protein 1 (HMGB1) was released from necrotic neurons via a NR2B‐mediated mechanism. HMGB1 was clinically associated with elevated ICP in patients and functionally promoted cerebral edema after TBI in mice. The detrimental effects of HMGB1 were mediated, at least in part, via activation of microglial toll‐like receptor 4 (TLR4) and the subsequent expression of the astrocytic water channel, aquaporin‐4 (AQP4). Genetic or pharmacological (VGX‐1027) TLR4 inhibition attenuated the neuroinflammatory response and limited post‐traumatic edema with a delayed, clinically implementable therapeutic window. Human and rodent tissue culture studies further defined the cellular mechanisms demonstrating neuronal HMGB1 initiates the microglial release of interleukin‐6 (IL‐6) in a TLR4 dependent mechanism. In turn, microglial IL‐6 increased the astrocytic expression of AQP4. Taken together, these data implicate microglia as key mediators of post‐traumatic brain edema and suggest HMGB1‐TLR4 signaling promotes neurovascular dysfunction after TBI. GLIA 2013;62:26–38