Neuroprotective, Anti-Inflammatory and Antifibrillogenic Offerings by Emodin against Alzheimer's Dementia: A Systematic Review.

Background: Alzheimer's disease (AD) is among the major causes of dementia in the elderly and exerts tremendous clinical, psychological and socio-economic constraints. Currently, there are no effective disease-modifying/retarding anti-AD agents. Emodin is a bioactive phytochemical with potent multimodal anti-inflammatory, antioxidant, and antifibrillogenic properties. In particular, emodin may result in significant repression of the pathogenic mechanisms underlying AD. The purpose of this review is to accumulate and summarize all the primary research data evaluating the therapeutic actions of emodin in AD pathogenesis. Methodology: The search, selection, and retrieval of pertinent primary research articles were systematically performed using a methodically designed approach. A variety of keyword combinations were employed on online scholarly web-databases. Strict preset inclusion and exclusion criteria were used to select the retrieved studies. Data from the individual studies were summarized and compiled into different sections, based upon their findings. Results: Cellular and animal research indicates that emodin exerts robust multimodal neuroprotection in AD. While emodin effectively prevents tau and amyloid-beta (Aß) oligomerization, it also mitigates their neurotoxicity by attenuating neuroinflammatory, oxidative, and bioenergetic defects. Evidences for emodin-mediated enhancements in memory, learning, and cognition were also found in the literature. Conclusion: Emodin is a potential anti-AD dietary supplement; however, further studies are warrantied to thoroughly understand its target players and mechanisms. Moreover, human clinical data on emodin-mediated amelioration of AD phenotype is largely lacking, and must be addressed in the future. Lastly, the safety of exogenously supplemented emodin must be thoroughly evaluated.

The Potential of Epigallocatechin Gallate in Targeting Cancer Stem Cells: A Comprehensive Review.

The dreadful scenario of cancer prevails due to the presence of cancer stem cells (CSCs), which contribute to tumor growth, metastasis, invasion, resistance to chemo- and radiotherapy, and recurrence. CSCs are a small subpopulation of cells within the tumor that are characterized by self-renewal capability and have the potential to manifest heterogeneous lineages of cancer cells that constitute the tumor. The major bioactive green tea polyphenol (-)-epigallocatechin gallate (EGCG) has been fruitful in downgrading cancer stemness signaling and CSC biomarkers in cancer progression. EGCG has been evidenced to maneuver extrinsic and intrinsic apoptotic pathways in order to decrease the viability of CSCs. Cancer stemness is intricately related to epithelial-mesenchymal transition (EMT), metastasis and therapy resistance, and EGCG has been evidenced to regress all these CSC-related effects. By inhibiting CSC characteristics EGCG has also been evidenced to sensitize the tumor cells to radiotherapy and chemotherapy. However, the use of EGCG in in vitro and in vivo cancer models raises concern about its bioavailability, stability and efficacy against spheroids raised from parental cells. Therefore, novel nano formulations of EGCG and adjuvant therapy of EGCG with other phytochemicals or drugs or small molecules may have a better prospect in targeting CSCs. However, extensive clinical research is still awaited to elucidate a full proof impact of EGCG in cancer therapy.

Dysregulation of delta Np63 alpha in squamous cell carcinoma and its therapeutic targeting.

The gene p63 has two isoforms -a full length transactivated isoform (TA) p63 and an amino-terminally truncated isoform, ∆Np63. DeltaNp63 alpha (∆Np63α) is the predominant splice variant of the isoform, ∆Np63 and is expressed in the basal layer of stratified epithelia. ∆Np63α that is normally essential for the epithelial lineage maintenance may be dysregulated in squamous cell carcinomas (SCCs). The pro-tumorigenic or antitumorigenic role of ∆Np63 is a highly contentious arena. ∆Np63α may act as a double-edged sword. It may either promote tumor progression, epithelial-mesenchymal transition, migration, chemoresistance, and immune-inflammatory responses, or inhibit the aforementioned phenomena depending upon cell type and tumor microenvironment. Several signaling pathways, transforming growth factor-ß, Wnt and Notch, as well as epigenetic alterations involving microRNAs, and long noncoding RNAs are regulated by ∆Np63α. This review has attempted to provide an in-depth insight into the role of ∆Np63α in the development of SCCs during different stages of tumor formation and how it may be targeted for therapeutic implications.

The Optimization and Analysis of a Triple-Fin Heterostructure-on-Insulator Fin Field-Effect Transistor with a Stacked High-k Configuration and 10 nm Channel Length.

The recent developments in the replacement of bulk MOSFETs with high-performance semiconductor devices create new opportunities in attaining the best device configuration with drive current, leakage current, subthreshold swing, Drain-Induced Barrier Lowering (DIBL), and other short-channel effect (SCE) parameters. Now, multigate FETs (FinFET and tri-gate (TG)) are advanced methodologies to continue the scaling of devices. Also, strain technology is used to gain a higher current drive, which raises the device performance, and high-k dielectric material is used to minimize the subthreshold current. In this work, we used stacked high-k dielectric materials in a TG n-FinFET with three fins and a 10 nm channel length, incorporating a three-layered strained silicon channel to determine the short-channel effects. Here, we replaced the gate oxide (SiO2) with a stacked gate oxide of 0.5 nm of SiO2 with a 0.5 nm effective oxide thickness of different high-k dielectric materials like Si3N4, Al2O3, ZrO2, and HfO2. It was found that the use of strained silicon and replacing only the SiO2 device with the stacked SiO2 and HfO2 device was more beneficial to obtain an optimized device with the least leakage and improved drive currents.

Nonprescription use of buprenorphine tablets among patients at a tertiary care addictive disorder treatment center in India: Observa-tions and implications.

OBJECTIVE: Nonprescribed use of drugs is a clinical and public health challenge fueled by diversion of controlled opioids like buprenorphine. In this study, we report the nonprescription use of buprenorphine and buprenorphine-naloxone for the first time in India. DESIGN: A cross-sectional observational study utilizing semistructured interviews. SETTING: A tertiary care addictive disorder treatment center in India, which provides inpatient and outpatient medically oriented care that includes agonist treatment (buprenorphine) or detoxification and antagonist treatment (naltrexone). PARTICIPANTS: Patients aged 18-65 years, registered at the center, and who had a history of current (within the past 6 months) nonprescription use of buprenorphine tablets were recruited. MAIN OUTCOME MEASURES: Participants were questioned about demographic and clinical factors and details of nonprescription use of buprenorphine and buprenorphine-naloxone using a structured questionnaire. Since both buprenorphine with naloxone and buprenorphine without naloxone are available and transacted on the street "loose" out of the blister packs, we were unable to differentiate the use of plain buprenorphine and a combination of buprenorphine- naloxone. RESULTS: A majority of the participants used nonprescribed tablets buprenorphine and buprenorphine-naloxone with an intent to control the withdrawal symptoms, and the reason for this use was that other patients shared their prescriptions of these medications. About half of the participants injected the tablets, and liquid pheniramine was most commonly used as the solvent for dissolving the tablets. A "high" was perceived by around half of those who injected. Participants reported knowing, on an average, around 13 peers who injected the tablet buprenorphine or -buprenorphine-naloxone. CONCLUSION: Nonprescription use of tablets buprenorphine and -buprenorphine-naloxone is a clinical concern and also an important public health issue. Geographical and systemic expansions of the availability of buprenorphine may reduce the "demand" for nonprescribed buprenorphine, while the opportunities for diversion from treatment centers can be minimized through more careful clinical prescriptions and monitoring practices.

Racial and Ethnic Disparities in Cardiac Reintervention After Pediatric Cardiac Surgical Procedures.

BACKGROUND: Children undergoing cardiac surgical procedures may require postoperative surgical or catheter-based reintervention before discharge. We examined racial/ethnic variations in reintervention and associated in-hospital death. METHODS: Children undergoing cardiac surgical procedures from 2004 to 2015 were identified in the Pediatric Health Information Systems (PHIS) database. Regression analysis measured associations between race/ethnicity, in-hospital death, and postoperative cardiac surgical or catheter-based reintervention (surgical/catheter reintervention). RESULTS: Of 124,263 patients, 8265 (6.7%) had a surgical/catheter reintervention. Black patients had fewer reinterventions (5.9% vs 6.7%) and higher in-hospital mortality (3.9% vs 2.7%, P < .01) than White patients. After adjusting for sociodemographic and illness severity indicators, Black patients remained less likely to receive surgical/catheter reintervention (adjusted hazard ratio [aHR], 0.89; 95% CI, 0.82-0.98) despite having similar risk of death after reintervention (adjusted odds ratio, 1.17; 95% CI, 0.98-1.41) compared with White patients. The risk of death without surgical/catheter reintervention was also higher for Black (aHR, 1.26; 95% CI, 1.08-1.47) and other race/ethnicity (aHR, 1.33; 95% CI, 1.13-1.57) patients than for White patients. Similar trends were demonstrated when mechanical circulatory support and cardiac transplantation were included as reinterventions. CONCLUSIONS: Patients of Black and other race/ethnicity undergoing pediatric cardiac surgical procedures are more likely to die without postoperative cardiac reintervention than White patients. Black patients are also less likely to receive reintervention despite no significant difference in mortality with reintervention. Further studies should evaluate etiologies and methods of addressing these disparities.

A cross-sectional study exploring the positive aspects of caregiving in opioid dependence and its relation with quality of life, social support, and caregivers' burden.

Background and Aims: Despite a large body of research linking caregiver burden and social support in substance dependence, positive aspects of caregiving in these disorders have received very minimal attention. This exploratory observational study aimed to assess the positive aspects of caregiving for opioid dependence and evaluate the association of these positive aspects with caregiver quality of life, burden, and social support. Methods: This cross-sectional study included 199 caregivers of patients with opioid dependence recruited through purposive sampling. Participants were assessed using the Scale for Positive Aspects of Caregiving Experience (SPACE), World Health Organization Quality of Life-BREF version, Family Burden Interview Schedule (FBIS), and Social Support Questionnaire. Results: Of the 199 caregivers recruited, a majority of the caregivers were middle-aged women. About two-thirds of the patients were currently using opioids (n = 135, 67.8%), while the remaining were abstinent. Among the SPACE domain scores, the mean was highest for motivation for the caregiving role (2.07), which was followed by self-esteem and social aspect of caring (2.04), caregiving personal gains (1.76), and caregiver satisfaction (1.65). Caregivers of patients currently abstinent experienced greater positive aspects of caregiving (SPACE mean item score 2.57 versus 1.62, P < 0.001), and lesser burden (FBIS mean score 13.4 versus 29.3, P < 0.001). Conclusion: Positive aspects of caregiving can be potentially utilized for better caregiver engagement in treatment and improved caregiver outcomes.

Neuroprotection by agmatine: Possible involvement of the gut microbiome?

Agmatine, an endogenous polyamine derived from L-arginine, elicits tremendous multimodal neuromodulant properties. Alterations in agmatinergic signalling are closely linked to the pathogeneses of several brain disorders. Importantly, exogenous agmatine has been shown to act as a potent neuroprotectant in varied pathologies, including brain ageing and associated comorbidities. The antioxidant, anxiolytic, analgesic, antidepressant and memory-enhancing activities of agmatine may derive from its ability to regulate several cellular pathways; including cell metabolism, survival and differentiation, nitric oxide signalling, protein translation, oxidative homeostasis and neurotransmitter signalling. This review briefly discusses mammalian metabolism of agmatine and then proceeds to summarize our current understanding of neuromodulation and neuroprotection mediated by agmatine. Further, the emerging exciting bidirectional links between agmatine and the resident gut microbiome and their implications for brain pathophysiology and ageing are also discussed.

Bis-Olefin Based Crystalline Schlenk Hydrocarbon Diradicals with a Triplet Ground State.

A modular approach for the synthesis of isolable crystalline Schlenk hydrocarbon diradicals from m-phenylene bridged electron-rich bis-triazaalkenes as synthons is reported. EPR spectroscopy confirms their diradical nature and triplet electronic structure by revealing a half-field signal. A computational analysis confirms the triplet state to be the ground state. As a proof-of-principle for the modular methodology, the 4,6-dimethyl-m-phenylene was further utilized as a coupling unit between two alkene motifs. The steric conjunction of the 4,6-dimethyl groups substantially twists the substituents at the nonbonding electron bearing centers relative to the central coupling m-phenylene motif. As a result, the spin delocalization is decreased and the exchange coupling between the two unpaired spins, hence, significantly reduced. Notably, 108 years after Schlenk's m-phenylene-bis(diphenylmethyl) synthesis as a diradical, for the first time we were able to isolate its derivative with the same spacer, i.e. m-phenylene, between two radical centers in a crystalline form.

Molecular mechanisms of neuroprotective offerings by rosmarinic acid against neurodegenerative and other CNS pathologies.

Rosmarinic acid (RA) is a natural phenolic compound present in culinary herbs of the Boraginaceae, Lamiaceae/Labiatae, and Nepetoideae families. While the medicinal applications of these plants have been known for ages, RA has only been relatively recently established as an effective ameliorative agent against various disorders including cardiac diseases, cancer, and neuropathologies. In particular, several studies have confirmed the neuroprotective potential of RA in multiple cellular and animal models, as well as in clinical studies. The neuroprotective effects mediated by RA stem from its multimodal actions on a plethora of cellular and molecular pathways; including oxidative, bioenergetic, neuroinflammatory, and synaptic signaling. In recent years, RA has garnered tremendous interest as an ideal therapeutic candidate for treating neurodegenerative diseases. This review first briefly discusses the pharmacokinetics of RA and then proceeds to detail the neuroprotective mechanisms of RA at the molecular levels. Finally, the authors focus on the ameliorative potential of RA against several central nervous system (CNS) disorders, ranging from neuropsychological stress and epilepsy to neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Parkinson's disease, Lewy body dementia, and amyotrophic lateral sclerosis.

Investigation of gate-engineered heterostructure tunnel field effect transistor as a label-free biosensor: a compact study.

In this article, the authors have articulated DC as well as transient response of a dielectric modulated gate-engineered heterostructure tunnel field effect transistor (GE-HTFET)-based biosensor for label-free detection. A low (direct) bandgap material, indium arsenide (InAs) has been selectively used in the source region to achieve improved band-to-band tunneling of carriers in the tunnel FET. The extended gate architecture is incorporated to stabilize the biomolecules in the nano-cavity aiding significant boost in ON current sensitivity. Using SILVACO ATLAS TCAD tool, the sensitivity of the biosensor is evaluated considering two important parameters possessed by bio-targets, i.e. dielectric constant (k) and charge density (N). A thorough analysis has been performed to show the impact of variation of dielectric constants and charge density of biomolecules over transfer characteristics of the device. ON current level (Ion) is eventually extracted which is considered here as the suitable sensing parameter of the device. Transient response to detect the settling time of Ion is also demonstrated here in presence of both positively and negatively charged bio-species with varying values of dielectric constant. Then ON current sensitivity is extracted accordingly for different locations of biomolecules within the nano-gap. Finally, an extensive comparative analysis of the present structure in terms of ON current sensitivity is shown to justify its sensing ability as compared to recently reported device structures.

Diet as a modifiable factor in tumorigenesis: Focus on microbiome-derived bile acid metabolites and short-chain fatty acids.

Several lines of evidences have implicated the resident microbiome as a key factor in the modulation of host physiology and pathophysiology; including the resistance to cancers. Gut microbiome heavily influences host lipid homeostasis by their modulatory effects on the metabolism of bile acids (BAs). Microbiota-derived BA metabolites such as deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) are implicated in the pathogeneses of various cancer types. The pathogenic mechanisms are multimodal in nature, with widespread influences on the host immunes system, cell survival and growth signalling and DNA damage. On the other hand, short-chain fatty acids (SCFAs) produced by the resident microbial activity on indigestible dietary fibres as well as during intermittent fasting regimens (such as the Ramazan fasting) elicit upregulation of the beneficial anti-inflammatory and anticancer pathways in the host. The present review first provides a brief overview of the molecular mechanisms of microbiota-derived lipid metabolites in promotion of tumour development. The authors then discuss the potential of diet as a therapeutic route for beneficial alteration of microbiota and the consequent changes in the production of SCFAs, particularly butyrate, in relation to the cancer prevention and treatment.

Complexity of Tumor Microenvironment: Therapeutic Role of Curcumin and Its Metabolites.

The tumor microenvironment (TME) is a complex network of cellular and non-cellular components surrounding the tumor. The cellular component includes fibroblasts, adipocytes, endothelial cells, and immune cells, while non-cellular components are tumor vasculature, extracellular matrix and signaling molecules. The tumor cells have constant close interaction with their surrounding TME components that facilitate their growth, survival, and metastasis. Targeting a complex TME network and its interaction with the tumor can offer a novel strategy to disrupt cancer cell progression. Curcumin, from turmeric rhizome, is recognized as a safe and effective natural therapeutic agent against multiple diseases including cancer. Here the effects of curcumin and its metabolites on tumor-TME interaction modulating ability have been described. Curcumin and its metabolites regulate TME by inhibiting the growth of its cellular components such as cancer-associated adipocytes, cancer-associated fibroblast, tumor endothelial cells, tumor-stimulating immune cells, and inducing anticancer immune cells. They also inhibit the interplay of tumor cells to TME by suppressing non-cellular components such as extracellular matrix, and associated tumor promoting signaling-pathways. In addition, curcumin inhibits the inflammatory environment, suppresses angiogenic factors, and increases antioxidant status in TME. Overall, curcumin has the capability to regulate TME components and their interaction with tumor cells.

Sneaking into the viral safe-houses: Implications of host components in regulating integrity and dynamics of rotaviral replication factories.

The biology of the viral life cycle essentially includes two structural and functional entities-the viral genome and protein machinery constituting the viral arsenal and an array of host cellular components which the virus closely associates with-to ensure successful perpetuation. The obligatory requirements of the virus to selectively evade specific host cellular factors while exploiting certain others have been immensely important to provide the platform for designing host-directed antiviral therapeutics. Although the spectrum of host-virus interaction is multifaceted, host factors that particularly influence viral replication have immense therapeutic importance. During lytic proliferation, viruses usually form replication factories which are specialized subcellular structures made up of viral proteins and replicating nucleic acids. These viral niches remain distinct from the rest of the cellular milieu, but they effectively allow spatial proximity to selective host determinants. Here, we will focus on the interaction between the replication compartments of a double stranded RNA virus rotavirus (RV) and the host cellular determinants of infection. RV, a diarrheagenic virus infecting young animals and children, forms replication bodies termed viroplasms within the host cell cytoplasm. Importantly, viroplasms also serve as the site for transcription and early morphogenesis of RVs and are very dynamic in nature. Despite advances in the understanding of RV components that constitute the viroplasmic architecture, knowledge of the contribution of host determinants to viroplasm dynamicity has remained limited. Emerging evidence suggests that selective host determinants are sequestered inside or translocated adjacent to the RV viroplasms. Functional implications of such host cellular reprogramming are also ramifying-disarming the antiviral host determinants and usurping the pro-viral components to facilitate specific stages of the viral life cycle. Here, we will provide a critical update on the wide variety of host cellular pathways that have been reported to regulate the spatial and temporal dynamicity of RV viroplasms. We will also discuss the methods used so far to study the host-viroplasm interactions and emphasize on the potential host factors which can be targeted for therapeutic intervention in the future.

Concat_CNN: A Model to Detect COVID-19 from Chest X-ray Images with Deep Learning.

COVID-19 is creating havoc on the lives of human beings all around the world. It continues to affect the normal lives of people. As number of cases are high, a cost effective and fast system is required to detect COVID-19 at appropriate time to provide the necessary healthcare. Chest X-rays have emerged as an easiest way to detect COVID-19 in no time as RT-PCR takes time to detect the infection. In this paper we propose a concatenation-based CNN model that will detect COVID-19 from chest X-rays. We have developed a multiclass classification problem which can detect and classify a chest X-ray image as either COVID + ve, or viral pneumonia, or normal. We have used chest X-rays collected from different open sources. To maintain class balancing, we took 500 images of COVID, 500 normal images, and 500 pneumonia images. We divided our dataset in training, validation, and test set in 70:10:20 ratio respectively. We used four CNNs as feature extractors from the images and concatenated their feature maps to get better efficiency of the network. After training our model for 5 folds, we have obtained around 96.31% accuracy, 95.8% precision, 92.99% recall, and 98.02% AUC. We have compared our work with state-of-the-art pretrained transfer learning algorithms and other state-of-the-art CNN models referred in different research papers. The proposed model (Concat_CNN) exhibits better accuracy than the state-of-the-art models. We hope our proposed model will help to classify chest X-rays effectively and help medical professionals with their treatment.

Interleukin-1ß activated c-FOS transcription factor binds preferentially to a specific allele of the matrix metalloproteinase-13 promoter and increases susceptibility to endometriosis.

Endometriosis is a benign gynecological condition characterized by increased growth, inflammation, invasion, and angiogenesis, partly regulated by a class of enzymes called matrix metalloproteinases (MMPs). The importance of a few MMPs, e.g., MMP-9, -3, and -7 has been studied in endometriosis progression. Although MMP-13 plays an essential role in bone regeneration and cancer, no report has been found on the part of MMP-13 and endometriosis progression. We found the upregulation of MMP-13 expression and activity in patients having endometriosis in the eastern Indian population. In addition, the -77A/G polymorphism of the MMP13 promoter (rs: 2252070) is associated with regulating transcription and subsequent susceptibility to disease. In eastern Indian case-control groups, the effect of the -77A/G single-nucleotide polymorphism on MMP13 promoter activity and its relationship with endometriosis susceptibility was studied. The AG genotype was shown to be more predisposed to endometriosis risk than the GG genotype (p: 0.02; odds ratio [OR]: 1.65, 95% confidence interval [CI]: 1.10-2.49), also AG genotype was more frequent in late-stage patients compared to early-stage (p: 0.03, OR: 2.0, 95% CI: 1.09-3.66). Furthermore, the MMP13 gene levels were greater in AA compared to GG individuals. Additionally, MMP13 promoter-reporter experiments in cultured endometrial epithelial cells and in silico analyses both demonstrated increased transcriptional activity near the G to A transition under basal/IL-1ß -induced/c-FOS overexpressed condition. Overall, c-FOS tighter binding to the A allele-carrying promoter enhances MMP13 transcription, which is further amplified by IL-1ß due to increased c-FOS phosphorylation, promoting MMP-13 production and endometriosis risk.

Chemokines driven ovarian cancer progression, metastasis and chemoresistance: Potential pharmacological targets for cancer therapy.

Ovarian cancer is a leading cause of death among women globally often characterized by poor prognosis and aggressive tumor growth. The therapeutic outcomes of ovarian cancer patients are majorly limited by the development of acquired chemo/radioresistance and the lack of targeted therapies. The tumor microenvironment (TME) comprises a diverse population of cells including adipocytes, fibroblasts, tumor cells, and immune cells which play an imperative role in promoting tumor growth, invasion, and malignant phenotypes of cancer cells. The cells present in TME secrete various inflammatory mediators including chemokines and cytokines, which regulate the tumor progression and metastasis. This review article highlights new insights about the general mechanisms associated with chemokines-mediated cell proliferation, inflammation, tumor initiation, progression, metastasis, chemoresistance, and immune evasion in ovarian cancer. We also discuss the microRNAs (miRNAs) regulating the oncogenic potential of chemokines. Overall, this is a comparatively less explored area that could provide important insights into ovarian cancer development and a promising avenue for targeted therapy of ovarian cancer.

Association of SAPAP3 allelic variants with symptom dimensions and pharmacological treatment response in obsessive-compulsive disorder.

Though several SAPAP3 gene knockout studies in mice have implicated its role in compulsivity, human studies have failed to demonstrate its association with obsessive-compulsive disorder (OCD). We examined the association between allelic variants of a single nucleotide polymorphism in the SAPAP3 gene (rs6662980) with specific aspects of the OCD phenotype. A total of 200 individuals with OCD were genotyped using the TaqMan assay. All participants were assessed using the Mini International Neuropsychiatric Interview and the Yale-Brown Obsessive-Compulsive Scale, and their response to serotonin reuptake inhibitors (SRIs) was evaluated over naturalistic treatment and follow-up. After correcting for multiple comparisons, the G allele at rs6662980 was found to be associated with contamination and washing symptoms (p = .003). Logistic regression analysis also showed that presence of the G allele predicted poor response to SRIs (odds ratio [OR] = 2.473, 95% confidence interval [1.157, 5.407], p = .021). Interaction between presence of the G allele and the Contamination and Washing factor score predicted greater SRI resistance (OR = 3.654, [2.761, 4.547], p = .004). We conclude that specific phenotypic manifestations of OCD, which include contamination and washing-related symptoms along with resistance to SRIs, may be affected by variations in the SAPAP3 gene. Limitations of the study are the lack of a dimensional measure for assessing OCD symptoms, the evaluation of treatment response over naturalistic follow-up, and that only a single locus in the SAPAP3 gene was examined. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Impact of anesthetics on oncogenic signaling network: a review on propofol and isoflurane.

Propofol as an intravenous anesthetic and isoflurane as an inhalational/volatile anesthetic continue to be an important part of surgical anesthetic interventions worldwide. The impact of these anesthetics on tumor progression, immune modulation, and survival rates of cancer patients has been widely investigated. Although most of the preclinical studies have provided a beneficial effect of propofol over isoflurane or other volatile anesthetics, several investigations have shown contradictory results, which warrant more preclinical and clinical studies. Propofol mostly exhibits antitumor properties, whereas isoflurane being a cost-effective anesthetic is frequently used. However, isoflurane has been also reported with protumorigenic activity. This review provides an overall perspective on the network of signaling pathways that may modulate several steps of tumor progression from inflammation, immunomodulation, epithelial-mesenchymal transition (EMT) to invasion, metastasis, angiogenesis, and cancer stemness and extracellular vesicles along with chemotherapeutic applications and clinical status of these anesthetics. A clear understanding of the mechanistic viewpoints of these anesthetics may pave the way for more prospective clinical trials with the ultimate goal of obtaining a safe and optimal anesthetic intervention that would prevent cancer recurrence and may influence better postoperative survival.

Rotavirus activates MLKL-mediated host cellular necroptosis concomitantly with apoptosis to facilitate dissemination of viral progeny.

Reprogramming the host cellular environment is an obligatory facet of viral pathogens to foster their replication and perpetuation. One of such reprogramming events is the dynamic cross-talk between viruses and host cellular death signaling pathways. Rotaviruses (RVs) have been reported to develop multiple mechanisms to induce apoptotic programmed cell death for maximizing viral spread and pathogenicity. However, the importance of non-apoptotic programmed death events has remained elusive in context of RV infection. Here, we report that RV-induced apoptosis accompanies another non-apoptotic mode of programmed cell death pathway called necroptosis to promote host cellular demise at late phase of infection. Phosphorylation of mixed lineage kinase domain-like (MLKL) protein indicative of necroptosis was observed to concur with caspase-cleavage (apoptotic marker) beyond 6 hr of RV infection. Subsequent studies demonstrated phosphorylated-MLKL to oligomerize and to translocate to plasma membrane in RV infected cells, resulting in loss of plasma membrane integrity and release of alarmin molecules e.g., high mobility group box protein 1 (HMGB1) in the extracellular media. Moreover, inhibiting caspase-cleavage and apoptosis could not fully rescue virus-induced cell death but rather potentiated the necroptotic trigger. Interestingly, preventing both apoptosis and necroptosis by small molecules significantly rescued virus-induced host cytopathy by inhibiting viral dissemination.