Comparative evaluation of the efficacy of the Pro AF Baby Gold and Kedo-S pediatric endodontic files for canal instrumentation, transportation, and centering ratio - A systematic review and meta-analysis.

BACKGROUND: Traditionally, pediatric endodontics lacked access to the full potential of rotary instruments. These instruments, designed for the permanent root canal system, often presented limitations when used in primary teeth. To address this, exclusive pediatric rotary files with regular improvements have been introduced, featuring superior cutting efficiency with a focus on precise alignment. This design offers the advantage of reduced risk of ledges, perforations, instrument separation, and canal transportation. This study aimed to compare and evaluate the effectiveness of Pro AF Baby Gold and Kedo-S rotary files in preparing primary tooth root canals during pulpectomy procedures through a meta-analysis. METHODOLOGY: The review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. The review searched electronic databases from 2000 to February 2024 for studies evaluating the efficacy of Pro AF Baby Gold and Kedo-S files in terms of canal instrumentation, transportation, and centering ratio. The Cochrane risk of bias (ROB)-2 tool assessed quality, with analyses conducted using RevMan software version 5.3. The standardized mean difference (SMD) served as the summary with a random effects model (P < 0.05). RESULTS: Out of the five studies identified through the eligibility criteria, three were deemed suitable for a meta-analysis, while all five were included in a qualitative synthesis. The quality assessment revealed a presence of moderate-to-low ROB. The pooled analysis using SMD did not show any statistically significant differences between the files, except for the centering ratio in the mesiobuccal canal, where the Kedo-S file performed slightly better. In addition, the absence of any significant asymmetry in the funnel plot suggests that there is likely no publication bias present in the data. CONCLUSION: Pro AF Baby Gold files can be used as an alternative adjunct in pediatric endodontics to Kedo-S files and manual files.Prospero Registration: CRD42023469406.

The F-box E3 ligase protein FBXO11 regulates EBNA3C-associated degradation of BCL6.

Most mature B-cell malignancies originate from the malignant transformation of germinal center (GC) B cells. The GC reaction appears to have a role in malignant transformation, in which a major player of the GC reaction is BCL6, a key regulator of this process. We now demonstrate that BCL6 protein levels were dramatically decreased in Epstein-Barr virus (EBV)-positive lymphoblastoid cell lines and Burkitt's lymphoma cell lines. Notably, BCL6 degradation was significantly enhanced in the presence of both EBNA3C and FBXO11. Furthermore, the amino-terminal domain of EBNA3C, which contains residues 50-100, interacts directly with FBXO11. The expression of EBNA3C and FBXO11 resulted in a significant induction of cell proliferation. Furthermore, BCL6 protein expression levels were regulated by EBNA3C via the Skp Cullin Fbox (SCF)FBXO11 complex, which mediated its ubiquitylation, and knockdown of FBXO11 suppressed the transformation of lymphoblastoid cell lines. These data provide new insights into the function of EBNA3C in B-cell transformation during GC reaction and raise the possibility of developing new targeted therapies against EBV-associated cancers. IMPORTANCE: The novel revelation in our study involves the suppression of BCL6 expression by the essential Epstein-Barr virus (EBV) antigen EBNA3C, shedding new light on our current comprehension of how EBV contributes to lymphomagenesis by impeding the germinal center reaction. It is crucial to note that while several EBV latent proteins are expressed in infected cells, the collaborative mechanisms among these proteins in regulating B-cell development or inducing B-cell lymphoma require additional investigation. Nonetheless, our findings carry significance for the development of emerging strategies aimed at addressing EBV-associated cancers.

Superior Mesenteric Artery Syndrome in an 11-Year-Old Boy: A Case Report.

Superior Mesenteric Artery Syndrome (SMAS) is a rare but potentially life-threatening condition caused by the compression of the duodenum by the superior mesenteric artery. We report a case of an 11-year-old male who complaint of abdominal pain and intermittent vomiting for last 3 weeks. Diagnosis of SMAS was made with the help of radiological findings. The patient was managed conservatively with nutritional support, prokinetic agents, and stomach decompression. After 2 weeks of treatment, the patient's symptoms improved, and he was discharged from the hospital.

Bisphenol-F and Bisphenol-S (BPF and BPS) Impair the Stemness of Neural Stem Cells and Neuronal Fate Decision in the Hippocampus Leading to Cognitive Dysfunctions.

Neurogenesis occurs throughout life in the hippocampus of the brain, and many environmental toxicants inhibit neural stem cell (NSC) function and neuronal generation. Bisphenol-A (BPA), an endocrine disrupter used for surface coating of plastic products causes injury in the developing and adult brain; thus, many countries have banned its usage in plastic consumer products. BPA analogs/alternatives such as bisphenol-F (BPF) and bisphenol-S (BPS) may also cause neurotoxicity; however, their effects on neurogenesis are still not known. We studied the effects of BPF and BPS exposure from gestational day 6 to postnatal day 21 on neurogenesis. We found that exposure to non-cytotoxic concentrations of BPF and BPS significantly decreased the number/size of neurospheres, BrdU+ (proliferating NSC marker) and MAP-2+ (neuronal marker) cells and GFAP+ astrocytes in the hippocampus NSC culture, suggesting reduced NSC stemness and self-renewal and neuronal differentiation and increased gliogenesis. These analogs also reduced the number of BrdU/Sox-2+, BrdU/Dcx+, and BrdU/NeuN+ co-labeled cells in the hippocampus of the rat brain, suggesting decreased NSC proliferation and impaired maturation of newborn neurons. BPF and BPS treatment increases BrdU/cleaved caspase-3+ cells and Bax-2 and cleaved caspase protein levels, leading to increased apoptosis in hippocampal NSCs. Transmission electron microscopy studies suggest that BPF and BPS also caused degeneration of neuronal myelin sheath, altered mitochondrial morphology, and reduced number of synapses in the hippocampus leading to altered cognitive functions. These results suggest that BPF and BPS exposure decreased the NSC pool, inhibited neurogenesis, induced apoptosis of NSCs, caused myelin degeneration/synapse degeneration, and impaired learning and memory in rats.

From Hypertension to Beyond: Unraveling the Diverse Mechanisms of Olmesartan in Disease Modulation.

Olmesartan, originally known for its antihypertensive properties, exhibits promising potential in addressing inflammation-mediated diseases. As an angiotensin II receptor blocker (ARB), Olmesartan influences pivotal pathways, including reactive oxygen species, cytokines, NF-κB, TNF-α, and MAPK. This suggests a viable opportunity for repurposing the drug in conditions such as ulcerative colitis, neuropathy, nephropathy, and cancer, as supported by multiple preclinical studies. Ongoing clinical trials, particularly in cardiomyopathy and nephropathy, suggest a broader therapeutic scope for Olmesartan. Repurposing efforts would entail comprehensive investigations using disease-specific preclinical models and dedicated clinical studies. The drug's established safety profile, wide availability, and well-understood ARB mechanism of action offer distinct advantages that could facilitate a streamlined repurposing process. In summary, Olmesartan's versatile impact on inflammation-related pathways positions it as a promising candidate for repurposing across various diseases. Ongoing clinical trials and the drug's favorable attributes enhance its appeal for further exploration and potential application in diverse medical contexts.

KSHV-encoded LANA bypasses transcriptional block through the stabilization of RNA Pol II in hypoxia.

IMPORTANCE: Hypoxia can induce the reactivation of Kaposi sarcoma-associated virus (KSHV), which necessitates the synthesis of critical structural proteins. Despite the unfavorable energetic conditions of hypoxia, KSHV utilizes mechanisms to prevent the degradation of essential cellular machinery required for successful reactivation. Our study provides new insights on strategies employed by KSHV-infected cells to maintain steady-state transcription by overcoming hypoxia-mediated metabolic stress to enable successful reactivation. Our discovery that the interaction of latency-associated nuclear antigen with HIF1α and NEDD4 inhibits its polyubiquitination activity, which blocks the degradation of RNA Pol II during hypoxia, is a significant contribution to our understanding of KSHV biology. This newfound knowledge provides new leads in the development of novel therapies for KSHV-associated diseases.

Ecological and Health Risk Assessment of Heavy Metals Bioaccumulation in Ganges Fish Near Varanasi, India.

Heavy metal contamination in river Ganga is one of the factors for deterioration in its water quality and also adds to human health risks. We designed our study to achieve a holistic approach by not only estimating the concentration of heavy metals (lead, manganese, chromium, and cadmium) in the river water at different sites based on human anthropogenic activities but also in the fishes residing in the same sites that are collected for human consumption on daily basis. We found that Ganga River in Varanasi is highly loaded with metals (PLI = 6.698). Mean concentration in water was 1.29 mg/L for Pb, 1.325 mg/L for Mn, 0.169 mg/L for Cr, and 0.161 mg/L for Cd, which were above the permissible limits stated by Environment Protection Agency (EPA) in drinking water. Fish, including exotic and invasive species, were collected from the wild and were processed for the presence of these metals in their tissues. Degree of heavy metal concentration followed liver > gills > muscles. The highest accumulation of Pb was observed in Carpio (Cyprinus carpio) liver (8.86 µg/g) and lowest in Baikari (Clupisoma garua) muscles (0.07 µg/g). Total target hazard quotient (THQ) value, i.e., hazard index (HI) showed values in following sequence: Cyprinus carpio > Oreochromis niloticus > Channa gachua > Johnius coitor > Mastacembelus armatus > Mystus tengara > Clupisoma garua. Maximum HI value was recorded in C. carpio, which is highly consumed fish by humans, hence, may be harmful to them.

Material matters: exploring the interplay between natural biomaterials and host immune system.

Biomaterials are widely used for various medical purposes, for instance, implants, tissue engineering, medical devices, and drug delivery systems. Natural biomaterials can be obtained from proteins, carbohydrates, and cell-specific sources. However, when these biomaterials are introduced into the body, they trigger an immune response which may lead to rejection and failure of the implanted device or tissue. The immune system recognizes natural biomaterials as foreign substances and triggers the activation of several immune cells, for instance, macrophages, dendritic cells, and T cells. These cells release pro-inflammatory cytokines and chemokines, which recruit other immune cells to the implantation site. The activation of the immune system can lead to an inflammatory response, which can be beneficial or detrimental, depending on the type of natural biomaterial and the extent of the immune response. These biomaterials can also influence the immune response by modulating the behavior of immune cells. For example, biomaterials with specific surface properties, such as charge and hydrophobicity, can affect the activation and differentiation of immune cells. Additionally, biomaterials can be engineered to release immunomodulatory factors, such as anti-inflammatory cytokines, to promote a tolerogenic immune response. In conclusion, the interaction between biomaterials and the body's immune system is an intricate procedure with potential consequences for the effectiveness of therapeutics and medical devices. A better understanding of this interplay can help to design biomaterials that promote favorable immune responses and minimize adverse reactions.

Tablet-Based Puzzle Game Intervention for Cognitive Function and Well-Being in Healthy Adults: Pilot Feasibility Randomized Controlled Trial.

Background: Promoting cognitive health is key to maintaining cognitive and everyday functions and preventing the risk of cognitive impairment or dementia. Existing scientific evidence shows the benefits of various training modalities on cognition. One way to promote cognitive health is through engagement in cognitive activities (eg, board and video games). Objective: This study aims to investigate the benefits of dynamic adaptive casual puzzle games on cognitive function and well-being in healthy adults and older people. Methods: A total of 12 adults and older people (female participants: n=6; mean age 58.92, SD 10.28 years; range 46-75 years) were included in this pilot randomized controlled trial. This study used a crossover design with two phases (8 weeks each) and three measurement waves (pretest, midtest, and posttest). The participants were randomly allocated either to the control or experimental group. In the control group, participants read newspapers between the pre- and midtest, then switched to cognitive training with puzzle games. In the experimental group, the interventions were reversed. Baseline measurements (pretest) were collected before the intervention. The interventions were delivered on tablet computers and took place unsupervised at participants' homes. Results: The outcome measures included global cognitive function, higher cognitive function, and emotional well-being at 3 time points (pretest, midtest, and posttest) using standardized neuropsychological tests. The participants showed improvements in their visual attention and visuospatial measures after the puzzle game intervention. Conclusions: The study showed that digital games are a feasible way to train cognition in healthy adults and older people. The algorithm-based dynamic adaption allows accommodations for persons with different cognitive levels of skill. The results of the study will guide future prevention efforts and trials in high-risk populations.

Insight into the Epigenetics of Kaposi's Sarcoma-Associated Herpesvirus.

Epigenetic reprogramming represents a series of essential events during many cellular processes including oncogenesis. The genome of Kaposi's sarcoma-associated herpesvirus (KSHV), an oncogenic herpesvirus, is predetermined for a well-orchestrated epigenetic reprogramming once it enters into the host cell. The initial epigenetic reprogramming of the KSHV genome allows restricted expression of encoded genes and helps to hide from host immune recognition. Infection with KSHV is associated with Kaposi's sarcoma, multicentric Castleman's disease, KSHV inflammatory cytokine syndrome, and primary effusion lymphoma. The major epigenetic modifications associated with KSHV can be labeled under three broad categories: DNA methylation, histone modifications, and the role of noncoding RNAs. These epigenetic modifications significantly contribute toward the latent-lytic switch of the KSHV lifecycle. This review gives a brief account of the major epigenetic modifications affiliated with the KSHV genome in infected cells and their impact on pathogenesis.

Insights into Diversity, Distribution, and Systematics of Rust Genus Puccinia.

Puccinia, which comprises 4000 species, is the largest genus of rust fungi and one of the destructive plant pathogenic rust genera that are reported to infect both agricultural and nonagricultural plants with severe illnesses. The presence of bi-celled teliospores is one of the major features of these rust fungi that differentiated them from Uromyces, which is another largest genus of rust fungi. In the present study, an overview of the current knowledge on the general taxonomy and ecology of the rust genus Puccinia is presented. The status of the molecular identification of this genus along with updated species numbers and their current statuses in the 21st century are also presented, in addition to their threats to both agricultural and nonagricultural plants. Furthermore, a phylogenetic analysis based on ITS and LSU DNA sequence data available in GenBank and the published literature was performed to examine the intergeneric relationships of Puccinia. The obtained results revealed the worldwide distribution of Puccinia. Compared with other nations, a reasonable increase in research publications over the current century was demonstrated in Asian countries. The plant families Asteraceae and Poaceae were observed as the most infected in the 21st century. The phylogenetic studies of the LSU and ITS sequence data revealed the polyphyletic nature of Puccinia. In addition, the presences of too short, too lengthy, and incomplete sequences in the NCBI database demonstrate the need for extensive DNA-based analyses for a better understanding of the taxonomic placement of Puccinia.

Total external ophthalmoplegia and orbital apex syndrome as first presenting feature of Rhabdomyosarcoma involving petrous part of the temporal bone: A case report.

INTRODUCTION AND IMPORTANCE: Rhabdomyosarcoma (RMS) can have various unusual presentations. We report an unusual presentation of RMS as orbital apex syndrome in a six-year-old boy involving the petrous part of the temporal bone. CASE PRESENTATION: A six-year-old boy presented with drooping of the left eyelid for seven days associated with headache, left-sided hearing loss, and nasal blockage. Contrast-enhanced magnetic resonance imaging (CE-MRI) brain and orbit revealed an ill-defined expansile vascular lesion centered at the petrous part of the left temporal bone with extension to the cavernous sinus, which was confirmed as RMS on histopathology and immunohistochemistry. The patient was managed by chemotherapy and radiotherapy. CLINICAL DISCUSSION: RMS is the most common aggressive malignant soft tissue tumor in the pediatric population. It accounts for 4-8 % of all malignancies in children below 15 years of age, with strong male preponderance. The most common site for RMS is head and neck (45 %), having maximum incidence during the first decade of life. CONCLUSION: Total external ophthalmoplegia in a child is an acute emergency; it should be properly worked up, and neuroimaging should always be advised. Prompt diagnosis and management by a multidisciplinary team can be both life and sight-saving.

The influence of tumor topography on the surgical outcome of craniopharyngiomas.

OBJECTIVE: Various topographical classifications for craniopharyngioma have been proposed based on their relationship with optic chiasm and the third ventricular floor. There is a paucity of literature evaluating the surgical outcome based on tumor topography. This study aims to compare the surgical outcomes of retrochiasmatic craniopharyngiomas (RCPs) and nonretrochiasmatic craniopharyngiomas (non-RCPs). METHODS: This retrospective study includes newly diagnosed patients with craniopharyngioma who underwent surgery between January 2000 and December 2015. Clinical features, the extent of resection (EOR), surgical outcomes, tumor recurrence, and progression-free survival (PFS) of craniopharyngiomas were compared with respect to their relationship to the optic chiasm and third ventricular floor. RESULTS: The authors identified RCPs in 104 and non-RCPs in 33 patients. RCPs were significantly larger and more associated with hydrocephalus than were non-RCPs (p < 0.001) at the time of diagnosis. Puget grade 2 hypothalamic involvement was more frequent with RCPs. EOR and PFS following either subtotal resection (p = 0.07) or gross-total resection (p = 0.7) were comparable between RCPs and non-RCPs. There was no significant difference in the postoperative visual outcome. Resection of RCPs resulted in higher postoperative hypopituitarism (64% vs 42%, p = 0.01) and hypothalamic dysfunction (18% vs 3%, p = 0.02). Location of the tumor, either retrochiasmatic (HR 0.5; 95% CI 0.14-2.2; p = 0.4) or nonretrochiasmatic (HR 1.3; 95% CI 0.3-5.5; p = 0.6), did not show association with recurrence. RCPs with extra- and intraventricular components (type 3b) had a higher incidence of postoperative hypothalamic morbidities (p = 0.01) and tumor recurrence (36% vs 19%; p = 0.05) during follow-up than the extraventricular (type 3a) RCP. Between prechiasmatic and infrachiasmatic/intrasellar craniopharyngiomas, EOR (p = 0.7), postoperative diabetes insipidus (p = 0.4), endocrinological outcome (p = 0.7), and recurrence (p = 0.1) were comparable. The patients with complex multicompartmental tumors had a lower rate of gross-total resection (25%, p = 0.02) and a higher incidence of tumor recurrence (75%, p = 0.004) than the rest. CONCLUSIONS: The tumor topography can influence the postoperative outcome. RCPs can be associated with a higher incidence of hypopituitarism and hypothalamic morbidities postoperatively. The influence of topography on EOR and tumor recurrence is controversial. However, this study did not find a significant difference in EOR and tumor recurrence between RCPs and non-RCPs. PFS and overall mortality are also comparable.

A wideband hybrid combiner design for ITER ion cyclotron radio frequency source.

The high-power radio frequency source for ion cyclotron heating and current drive of ITER tokamak consists of two identical 1.5 MW amplifier chains. These two chains will be combined using a wideband hybrid combiner with adequate coupling flatness, phase balance, return loss, and isolation response to generate 2.5 MW radio frequency (RF) power in the frequency range of 36 to 60 MHz. As part of the in-house development program at ITER-India, a wideband hybrid combiner with coupling flatness and return loss/isolation better than 0.4 and -25 dB, respectively, has been simulated. A detailed analysis for matched load performance of the hybrid combiner for the output power level of 3 MW as well as mismatched load performance for load power of 2.5 MW with voltage standing wave ratio 2.0 and 3.0 MW with voltage standing wave ratio 1.5 has been performed. Based on the simulation, a prototype model was in-house fabricated, and the simulated results have been validated experimentally in splitter and combiner mode. To evaluate performance as a combiner, two solid-state power amplifiers were combined through the prototype combiner for input power levels up to 2.5 kW on matched and mismatched load conditions. In the power splitter experiment, the RF power level up to 1.5 MW from a single amplifier chain was split through the prototype combiner to be dumped in the high power loads in the frequency range of 36 to 60 MHz.

Bisphenol-A (BPA) Impairs Hippocampal Neurogenesis via Inhibiting Regulation of the Ubiquitin Proteasomal System.

The ubiquitin-proteasome system (UPS) controls protein homeostasis to maintain cell functionality and survival. Neurogenesis relies on proteasome function, and a defective proteasome system during brain development leads to neurological disorders. An endocrine-disrupting xenoestrogen bisphenol-A (BPA) used in plastic products adversely affects human health and causes neurotoxicity. Previously, we reported that BPA reduces neural stem cells (NSCs) proliferation and differentiation, impairs myelination and mitochondrial protein import, and causes excessive mitochondrial fragmentation leading to cognitive impairments in rats. Herein, we examined the effect(s) of prenatal BPA exposure on UPS functions during NSCs proliferation and differentiation in the hippocampus. Rats were orally treated with 40 µg/kg body weight BPA during day 6 gestation to day 21 postnatal. BPA significantly reduced proteasome activity in a cellular extract of NSCs. Immunocytochemistry exhibited a significant reduction of 20S proteasome/Nestin+ and PSMB5/Nestin+ cells in NSCs culture. BPA decreased 20S/Tuj1+ and PSMB5/Tuj1+ cells, indicating disrupted UPS during neuronal differentiation. BPA reduced the expression of UPS genes, 20S, and PSMB5 protein levels and proteasome activity in the hippocampus. It significantly reduced overall protein synthesis by the loss of Nissl substances in the hippocampus. Pharmacological activation of UPS by a bioactive triterpenoid 18α-glycyrrhetinic acid (18α GA) caused increased proteasome activities, significantly increased neurosphere size and number, and enhanced NSCs proliferation in BPA exposed culture, while proteasome inhibition by MG132 further aggravates BPA-mediated effects. In silico studies demonstrated that BPA strongly binds to catalytic sites of UPS genes (PSMB5, TRIM11, Parkin, and PSMD4) which may result in UPS inactivation. These results suggest that BPA significantly reduces NSCs proliferation by impairing UPS, and UPS activation by 18α GA could suppress BPA-mediated neurotoxicity and exerts neuroprotection.

Targeting Kaposi's sarcoma associated herpesvirus encoded protease (ORF17) by a lysophosphatidic acid molecule for treating KSHV associated diseases.

Kaposi's sarcoma associated herpesvirus (KSHV) is causative agent of Kaposi's sarcoma, Multicentric Castleman Disease and Pleural effusion lymphoma. KSHV-encoded ORF17 encodes a protease which cleaves -Ala-Ala-, -Ala-Ser- or -Ala-Thr-bonds. The protease plays an important role in assembly and maturation of new infective virions. In the present study, we investigated expression pattern of KSHV-encoded protease during physiologically allowed as well as chemically induced reactivation condition. The results showed a direct and proportionate relationship between ORF17 expression with reactivation time. We employed virtual screening on a large database of natural products to identify an inhibitor of ORF17 for its plausible targeting and restricting Kaposi's sarcoma associated herpesvirus assembly/maturation. A library of 307,814 compounds of biological origin (A total 481,799 structures) has been used as a screen library. 1-oleoyl-2-hydroxy-sn-glycero-3-phospho-(1'-myo-inositol) was highly effective against ORF17 in in-vitro experiments. The screened compound was tested for the cytotoxic effect and potential for inhibiting Kaposi's sarcoma associated herpesvirus production upon induced reactivation by hypoxia, TPA and butyric acid. Treatment of reactivated KSHV-positive cells with 1-oleoyl-2-hydroxy-sn-glycero-3-phospho-(1'-myo-inositol) resulted in significant reduction in the production of Kaposi's sarcoma associated herpesvirus. The study identified a lysophosphatidic acid molecule for alternate strategy to inhibit KSHV-encoded protease and target Kaposi's sarcoma associated herpesvirus associated malignancies.

A Comprehensive Account of the Rust Genus Skierka (Skierkaceae).

The rust genus Skierka belonging to the phylum Basidiomycota was described in 1900 by Raciborski with Skierka canarii as the type species. The published literature on this rust genus reveals its ambiguity in taxonomic placement. It was challenging to taxonomically delineate and precisely identify each species within this genus due to the species sharing some common characteristics. The latest studies based on morphology taxonomy and molecular characteristics, however, have solved this puzzle now and placed this genus in its new family Skierkaceae. To understand all about the genus Skierka, this compilation was carried out to unveil the general characteristics, history, diversity, distribution, ecology, morphology and molecular taxonomy of different species of Skierka. After exploring 14 species of Skierka, it was observed that this genus is distributed in seven plant families in 19 countries all over the world. The genus appears to be well-represented in Asian and South American counties. This rust has not been reported from any European countries to date. The morpho-taxonomy of all species is well studied, but molecular analyses are still required. Only two species of the genus namely S. robusta and S. diploglottidis were identified based molecular analyses. Therefore, further studies should be focused on epitypifying the taxa that are too old and updating their taxonomy based on molecular, biochemical, and physiological aspects along with morphological characteristics. Multiple analytical methods should be considered when dealing with multi-locus datasets. This will increase our understanding of the diversity, distribution, and identification of these rust fungi.

Epigenetic Reprogramming of Kaposi's Sarcoma-Associated Herpesvirus during Hypoxic Reactivation.

The biphasic life cycle (latent and lytic) of Kaposi's sarcoma-associated Herpesvirus (KSHV) is regulated by epigenetic modification of its genome and its associated histone proteins. The temporal events driving epigenetic reprogramming of the KSHV genome on initial infection to establish latency has been well studied, but the reversal of these epigenetic changes during lytic replication, especially under physiological conditions such as hypoxia, has not been explored. In this study, we investigated epigenetic reprogramming of the KSHV genome during hypoxic reactivation. Hypoxia induced extensive enrichment of both transcriptional activators and repressors on the KSHV genome through H3K4Me3, H3K9Me3, and H3K27Me3, as well as histone acetylation (H3Ac) modifications. In contrast to uniform quantitative enrichment with modified histones, a distinct pattern of RTA and LANA enrichment was observed on the KSHV genome. The enrichment of modified histone proteins was due to their overall higher expression levels, which was exclusively seen in KSHV-positive cells. Multiple KSHV-encoded factors such as LANA, RTA, and vGPCR are involved in the upregulation of these modified histones. Analysis of ChIP-sequencing for the initiator DNA polymerase (DNAPol1α) combined with single molecule analysis of replicated DNA (SMARD) demonstrated the involvement of specific KSHV genomic regions that initiate replication in hypoxia.

HPV18 oncoproteins driven expression of PKM2 reprograms HeLa cell metabolism to maintain aerobic glycolysis and viability.

The molecular basis of human papillomavirus (HPV)-mediated cellular immortalization and malignant transformation has illustrated an indispensable role of viral E6/E7-oncoproteins. However, the impact of viral-oncoproteins on the metabolic phenotype of cancer cells remains ambiguous. We showed silencing of HPV18-encoded E6/E7-oncoprotein significantly reduced glucose consumption, lactate production, ATP level and viability. Silencing of HPV18-encoded E6/E7 in HeLa cells significantly down-regulated expression and activity of HK1, HK2, LDHA, and LDHB. Interestingly, there was an increased pyruvate kinase activity due to switch in expression from PKM2 isoform to PKM1. The switch in favor of alternatively spliced isoform PKM1, was regulated by viral-E6/E7-oncoprotein by inhibiting the c-Myc/hnRNP-axis. Further, the near absence of the PKM1 protein despite an adequate amount of PKM1 mRNA in HeLa cells was due to its proteasomal degradation. Our results suggests HPV18-encoded E6/E7 driven preferential expression of PKM2 is essential to support aerobic glycolysis and cell proliferation. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-022-00776-w.

Assessment of Oral Health-Related Quality of Life among Kutia Kandha Tribes of Odisha.

Aim and Objectives: Among the 75 listed particularly vulnerable tribal groups (PVTG), the highest number is found in Odisha. They do not have proper access to oral health-care services and at-risk to various oral conditions and lesions. Hence, the purpose of the study was to assess the oral health quality of life and its association with different factors of the Kutia Kandha tribal population. Materials and Methodology: A cross-sectional study was channeled among 600 Kutia Kandha tribe of Odisha. The oral health impact profile (OHIP-14) questionnaire was used to check the oral health-related quality of life. Number and percentages were derived using Microsoft Excel and for inferential statistics, a model was developed using multivariable logistic regression using STATA software. P was set at 0.05, which was considered to be statistically significant. Results: Total sample composed of 330 men and 270 women with a mean age of 40.62 ± 16.29 years. Smoking was seen among 19.8% of tribal people had smoking habit and 72.33% (n = 434) of the study group consumed smokeless tobacco. Only a few used fluoridated (3.8%) dentifrice. The mean OHIP score of the tribe was 30.67 ± 4.514 and about 65% of participants reported poor oral health quality of life scores. Conclusion: The oral health quality of life of the tribe is poor and the prevalence of tobacco among the target population because of the unavailability of dental services. Proper health education and motivation can be acknowledged to this group are required to improve their oral health.