Recent Studies Research Articles

Molecular Mechanisms and Therapeutic Potential of Resolvins in Cancer - Current Status and Perspectives.

Resolvins are specialized pro-resolving mediators derived from omega-3 fatty acids that can suppress several cancer-related molecular pathways, including important activation of transcription parameters in the tumor cells and their microenvironment, inflammatory cell infiltration, cytokines as well as chemokines. Recently, an association between resolvins and an important anti-inflammatory process in apoptotic tumor cell clearance (efferocytosis) was shown. The inflammation status or the oncogene activation increases the risk of cancer development via triggering the transcriptional agents, including nuclear factor kappa-light-chain-enhancer of activated B cells by generating the pro-inflammatory lipid molecules and infiltrating the tumor cells along with the high level of pro-inflammatory signaling. These events can cause an inflammatory microenvironment. Resolvins might decrease the leukocyte influx into the inflamed tissues. It is widely accepted that resolvins prohibit the development of debris-triggered cancer via increasing the clearance of debris, especially by macrophage phagocytosis in tumors without any side effects. Resolvins D2, D1, and E1 might suppress tumor-growing inflammation by activation of macrophages clearance of cell debris in the tumor. Resolvin D5 can assist patients with pain during treatment. However, the effects of resolvins as anti-inflammatory mediators in cancers are not completely explained. Thus, based on the most recent studies, we tried to summarize the most recent knowledge on resolvins in cancers.

Polyphenolic Nano-formulations: A New Avenue against Bacterial Infection.

The gradual emergence of new bacterial strains impervious to one or more antibiotics necessitates discovering and applying natural alternatives. Among natural products, various polyphenols exhibit antibacterial activity. However, polyphenols with biocompatible and potent antibacterial characteristics are limited due to low aqueous solubility and bioavailability; therefore, recent studies are considering new polyphenol formulations. Nanoformulations of polyphenols, especially metal nanoparticles, are currently being investigated for their potential antibacterial activity. Nanonization of such products increases their solubility and helps attain a high surface-to-volume ratio and, therefore, a higher reactivity of the nanonized products with better remedial potential than nonnanonized products. Polyphenolic compounds with catechol and pyrogallol moieties efficiently bond with many metal ions, especially Au and Ag. These synergistic effects exhibit antibacterial pro-oxidant ROS generation, membrane damage, and biofilm eradication. This review discusses various nano-delivery systems for considering polyphenols as antibacterial agents.

Computational Advancement towards the Identification of Natural Inhibitors for Dengue Virus: A Brief Review.

Viral infectious illnesses represent a severe hazard to human health due to their widespread incidence worldwide. Among these ailments, the dengue virus (DENV) infection stands out. World Health Organization (WHO) estimates that DENV infection affects ~400 million people each year, with potentially fatal symptoms showing up in 1% of the cases. In several instances, academic and pharmaceutical researchers have conducted several pilot and clinical studies on a variety of topics, including viral epidemiology, structure and function analyses, infection source and route, therapeutic targets, vaccinations, and therapeutic drugs. Amongst Takeda, TAK-003, Sanofi, Dengvaxia®, and Butantan/NIH/Merck, Dengvaxia® (CYD-TDV) is the only licensed vaccination yet; however, the potential inhibitors are under development. The biology and evolution of DENVs are briefly discussed in this review, which also compiles the most recent studies on prospective antiviral targets and antiviral candidates. In conclusion, the triumphs and failures have influenced the development of anti-DENV medications, and the findings in this review article will stimulate more investigation.

Recombinant Antibody Fragments for Neurological Disorders: An Update.

Recombinant antibody fragments are promising alternatives to full-length immunoglobulins, creating big opportunities for the pharmaceutical industry. Nowadays, antibody fragments such as antigen-binding fragments (Fab), single-chain fragment variable (scFv), single-domain antibodies (sdAbs), and bispecific antibodies (bsAbs) are being evaluated as diagnostics or therapeutics in preclinical models and in clinical trials. Immunotherapy approaches, including passive transfer of protective antibodies, have shown therapeutic efficacy in several animal models of Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), Huntington's disease (HD), transmissible spongiform encephalopathies (TSEs) and multiple sclerosis (MS). There are various antibodies approved by the Food and Drug Administration (FDA) for treating multiple sclerosis and two amyloid beta-specific humanized antibodies, Aducanumab and Lecanemab, for AD. Our previous review summarized data on recombinant antibodies evaluated in pre-clinical models for immunotherapy of neurodegenerative diseases. Here, we explore recent studies in this fascinating research field, give an update on new preventive and therapeutic applications of recombinant antibody fragments for neurological disorders and discuss the potential of antibody fragments for developing novel approaches for crossing the blood-brain barrier (BBB) and targeting cells and molecules of interest in the brain.

Potential Correlation between Gene Mutations and Metabolic Changes in Acute Myeloid Leukemia

Abstract: Acute myeloid leukemia (AML) is a common type of leukemia. However, the understanding of AML remains insufficient. The pathological progression of AML is closely related to chromosome abnormalities and genetic mutations. Gene mutation is an important factor in the pathogenesis of AML and a potential cause of drug resistance. Recent studies have shown that gene mutations in AML can cause metabolic changes. Metabolites, as downstream products of human physiological activities, can amplify physiological and disease-related signals. Therefore, the analysis of metabolite markers related to gene mutations can be used for early prediction of the occurrence of the disease. This review describes the types and significance of AML gene mutations and analyzes the characteristics of metabolic changes related to gene mutations.

Pharmacoeconomic Aspects of Diabetes Mellitus: Outcomes and Analysis of Health Benefits Approach.

Pharmacoeconomics is an important tool for investigating and restructuring healthcare policies. In India, recent statistical studies have shown that the number of diabetic patients is rapidly increasing in the rural, middle and upper-class settings. The aim of this review is to call attention towards the need to carry out pharmacoeconomic studies for diabetes mellitus and highlight the outcome of these studies on healthcare. A well-structured literature search from PubMed, Embase, Springer, ScienceDirect, and Cochrane was done. Studies that evaluated the cost-effectiveness of various anti-diabetic agents for type 2 diabetes were eligible for inclusion in the analysis and review. Two independent reviewers sequentially assessed the titles, abstracts, and full articles to select studies that met the predetermined inclusion and exclusion criteria for data abstraction. Any discrepancies between the reviewers were resolved through consensus. By employing search terms such as pharmacoeconomics, diabetes mellitus, cost-effective analysis, cost minimization analysis, cost-utility analysis, and cost-benefit analysis, a total of 194 papers were gathered. Out of these, 110 papers were selected as they aligned with the defined search criteria and underwent the removal of duplicate entries. This review outlined four basic pharmacoeconomic studies carried out on diabetes mellitus. It gave a direction that early detection, patient counseling, personalized medication, appropriate screening intervals, and early start of pharmacotherapy proved to be a cost-effective as well as health benefits approach.

Cancer Pathways Targeted by Berberine: Role of microRNAs.

Cancer is a complex and heterogeneous malignant disease. Due to its multifactorial nature, including progressive changes in genetic, epigenetic, transcript, and protein levels, conventional therapeutics fail to save cancer patients. Evidence indicates that dysregulation of microRNA (miRNA) expression plays a crucial role in tumorigenesis, metastasis, cell proliferation, differentiation, metabolism, and signaling pathways. Moreover, miRNAs can be used as diagnostic and prognostic markers and therapeutic targets in cancer. Berberine, a naturally occurring plant alkaloid, has a wide spectrum of biological activities in different types of cancers. Inhibition of cell proliferation, metastasis, migration, invasion, and angiogenesis, as well as induction of cell cycle arrest and apoptosis in cancer cells, is reported by berberine. Recent studies suggested that berberine regulates many oncogenic and tumor suppressor miRNAs implicated in different phases of cancer. This review discussed how berberine inhibits cancer growth and propagation and regulates miRNAs in cancer cells. And how berberine-mediated miRNA regulation changes the landscape of transcripts and proteins that promote or suppress cancer progression. Overall, the underlying molecular pathways altered by berberine and miRNA influencing the tumor pathophysiology will enhance our understanding to combat the malignancy.

Potential Neuroprotective Role of Neurotrophin in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major global health issue that affects millions of people every year. It is caused by any form of external force, resulting in temporary or permanent impairments in the brain. The pathophysiological process following TBI usually involves excitotoxicity, mitochondrial dysfunction, oxidative stress, inflammation, ischemia, and apoptotic cell death. It is challenging to find treatment for TBI due to its heterogeneous nature, and no therapeutic interventions have been approved thus far. Neurotrophins may represent an alternative approach for TBI treatment because they influence various functional activities in the brain. The present review highlights recent studies on neurotrophins shown to possess neuroprotective roles in TBI. Neurotrophins, specifically brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have demonstrated reduced neuronal death, alleviated neuroinflammatory responses and improved neurological functions following TBI via their immunomodulatory, anti-inflammatory and antioxidant properties. Further studies are required to ensure the efficacy and safety of neurotrophins to be used as TBI treatment in clinical settings.

Medical-Knowledge-Based Graph Neural Network for Medication Combination Prediction.

Medication combination prediction (MCP) can provide assistance for experts in the more thorough comprehension of complex mechanisms behind health and disease. Many recent studies focus on the patient representation from the historical medical records, but neglect the value of the medical knowledge, such as the prior knowledge and the medication knowledge. This article develops a medical-knowledge-based graph neural network (MK-GNN) model which incorporates the representation of patients and the medical knowledge into the neural network. More specifically, the features of patients are extracted from their medical records in different feature subspaces. Then these features are concatenated to obtain the feature representation of patients. The prior knowledge, which is calculated according to the mapping relationship between medications and diagnoses, provides heuristic medication features according to the diagnosis results. Such medication features can help the MK-GNN model learn optimal parameters. Moreover, the medication relationship in prescriptions is formulated as a drug network to integrate the medication knowledge into medication representation vectors. The results reveal the superior performance of the MK-GNN model compared with the state-of-the-art baselines on different evaluation metrics. The case study manifests the application potential of the MK-GNN model.

Fear of Happiness: Description, Causes and Prevention

Studies in mental health is to increase the positive emotions of the person and to reduce the negative emotions, beliefs and thoughts. Especially after positive psychology, many studies have been carried out to ensure that individuals have positive emotions. However, in recent studies, it has been determined that individuals avoid not only negative emotions but also positive emotions. Thus, you suppress your positive emotions because of fear of happiness. The individual's beliefs and cultural values also affect mental health. The person is afraid of being happy because of these beliefs and cultural values. Fear of happiness is the avoidance of happines. When people believe thet unhappiness will come immediately after happiness or that the environment will be harmed after being happy, fear of happiness occurs. Fear of happiness harms both the mental health and social relations. Morever, fear of happiness is associated with alexithymia, anxiety, stress, fear of compassion, antisocial, cognitive distortions related to relationships, panic disorder and especially depression. It is extremely important to know and define the fear of happiness for an effective treatment interventions. Fear of happiness rests in maladaptive schemas in early life, not meeting their needs warmly and sincerely in childhood, punishing them when they experience positive emotions, and growing up in a family with unhealthy family patterns. In this study, it is aimed to define fear of happiness, to determine the protective and risk factors, to determine the causative factors, to explain the related concepts, and so to raise awareness about fear of happiness.

Delayed effects of cigarette graphic warning labels on smoking behavior.

Graphic warning labels (GWLs) are widely employed to communicate smoking-related health risks; however, their implementation in the US has been held back by concerns about their efficacy. Most GWLs elicit a high level of emotional reaction (ER). The extent to which ER contributes to GWLs efficacy in improving smoking outcomes is a subject of debate. Our recent study showed poorer efficacy of the high-ER GWLs versus the low-ER ones during a month-long naturalistic exposure. Whether GWL effects persist after discontinuing the exposure remains unclear. We conducted a secondary analysis to investigate the delayed effects of GWLs on smoking severity in adult smokers. The number of cigarettes smoked per day (CPD) was measured immediately as well as 4 weeks after the end of a month-long exposure to high-ER versus low-ER GWLs. Participants indicated their subjective feeling of being relieved from having to see the GWLs. We found a significant reduction in CPD from the immediate to the 4-week post-exposure timepoint. There was no difference in CPD reduction between the high-ER and low-ER groups.Subjective sense of relief from GWL exposure was associated with greater CPD reduction in the high-ER group, but not the low-ER group. Our study suggests lasting impact of GWLs on smoking behavior. The findings may be particularly important to high-arousal GWLs, which appear less effective in reducing smoking during active exposure. Whether GWLs that evoke higher ER are more effective remains inconclusive. We recently showed that high-ER GWLs are less effective than low-ER ones in reducing smoking during continuous exposure. Here, we found evidence of delayed GWL effects such that smoking decreased from immediately to four weeks after the end of GWL exposure. Feeling of relief from GWL exposure was associated greater smoking reduction in the high-ER group. We suggest that continuously exposing smokers to high-ER GWLs that have been well remembered may be unnecessary and counterproductive.

Dynamics of drug delivery determines course of evolution of antibiotic responses in bacteria.

To adjust to sudden shifts in conditions, microbes possess regulated genetic mechanisms that sense environmental challenges and induce the appropriate responses. The initial evolution of microbes in new environments is thought to be driven by regulatory mutations, but it is not clear how this evolution is affected by how quickly conditions change (i.e. dynamics). Here, we perform experimental evolution on continuous cultures of tetracycline resistant E. coli in different dynamical regimens of drug administration. We find that cultures evolved under gradually increasing drug concentrations acquire fine- tuning mutations adapting an alternative efflux pump to tetracycline. However, cultures that are instead periodically exposed to large drug doses evolve transposon insertions resulting in loss of regulation of the main mechanism of tetracycline resistance. A mathematical model shows that sudden drug exposures overwhelm regulated responses, which cannot induce resistance fast enough. These results help explain the frequent loss of regulation of resistance in clinical pathogens.

A Statistical Framework for Analysis of Trial-Level Temporal Dynamics in Fiber Photometry Experiments.

Fiber photometry has become a popular technique to measure neural activity in vivo, but common analysis strategies can reduce detection of effects because they condense within-trial signals into summary measures, and discard trial-level information by averaging across-trials. We propose a novel photometry statistical framework based on functional linear mixed modeling, which enables hypothesis testing of variable effects at every trial time-point, and uses trial-level signals without averaging. This makes it possible to compare the timing and magnitude of signals across conditions while accounting for between-animal differences. Our framework produces a series of plots that illustrate covariate effect estimates and statistical significance at each trial time-point. By exploiting signal autocorrelation, our methodology yields joint 95% confidence intervals that account for inspecting effects across the entire trial and improve the detection of event-related signal changes over common multiple comparisons correction strategies. We reanalyze data from a recent study proposing a theory for the role of mesolimbic dopamine in reward learning, and show the capability of our framework to reveal significant effects obscured by standard analysis approaches. For example, our method identifies two dopamine components with distinct temporal dynamics in response to reward delivery. In simulation experiments, our methodology yields improved statistical power over common analysis approaches. Finally, we provide an open-source package and analysis guide for applying our framework.

Cellular Transdifferentiation: A Crucial Mechanism of Fibrosis in Systemic Sclerosis.

Systemic Sclerosis (SSc) is a systemic autoimmune disease of unknown etiology with a highly complex pathogenesis that despite extensive investigation is not completely understood. The clinical and pathologic manifestations of the disease result from three distinct processes: 1) Severe and frequently progressive tissue fibrosis causing exaggerated and deleterious accumulation of interstitial collagens and other extracellular matrix molecules in the skin and various internal organs; 2) extensive fibroproliferative vascular lesions affecting small arteries and arterioles causing tissue ischemic alterations; and 3) cellular and humoral immunity abnormalities with the production of numerous autoantibodies, some with very high specificity for SSc. The fibrotic process in SSc is one of the main causes of disability and high mortality of the disease. Owing to its essentially universal presence and the severity of its clinical effects, the mechanisms involved in the development and progression of tissue fibrosis have been extensively investigated, however, despite intensive investigation, the precise molecular mechanisms have not been fully elucidated. Several recent studies have suggested that cellular transdifferentiation resulting in the phenotypic conversion of various cell types into activated myofibroblasts may be one important mechanism. Here, we review the potential role that cellular transdifferentiation may play in the development of severe and often progressive tissue fibrosis in SSc.

Role of Circular RNAs in Prostate Cancer.

This study aims to summarize the current literature to demonstrate the importance of circular RNAs (circRNAs) in multiple aspects of prostate cancer (PCa) occurrence, progression, and treatment resistance and explore the potential role in therapeutic strategies aimed at targeting this molecule in PCa. The relevant literature from PubMed and Medline databases is reviewed in this article. Non-coding RNA has been proven to play a vital role in regulating tumor progression. Among them, circular RNA plays a more unique role due to its nonlinear structure. Lots of circRNAs were found to be differentially expressed in PCa and regulate cell signaling pathways by regulating particular gene expressions. Recent studies have demonstrated that circRNAs are associated with the chemoresistance of urinary tumors, suggesting that circRNAs might be a novel therapeutic target and a marker for therapeutic response and prognosis assessment. The potential crosstalk of circRNAs modifications in PCa development, therapy, and regulation of tumor metabolism is portrayed in this review. However, more preclinical and clinical trials of this targeted strategy are necessary for the treatment of urinary tumors.

Diphenyl Ethers: Isolation, Bioactivities and Biosynthesis

Abstract: Diphenyl ethers (DPEs) are mainly produced by microorganisms and plants. The chemical structure of DPEs is relatively simple, and all of these compounds have the structure of biphenyl ethers in their chemical structure, the difference being the difference in the substituents on the benzene ring. Several recent studies have shown antibacterial, antioxidant, antitumor, antitumor, antihemolytic, neuroprotective, and anti-Alzheimer effects. DPEs could be candidate compounds for the treatment of Alzheimer's disease, by inhibiting the aggregation of Aβ42. Many DPEs from natural products exhibit good biological activity and they play an important role in the control of microbial infections. Diphenyl ethers have a wide range of applications and research value in the fields of pesticides, pharmaceuticals, textiles, household products, and public health. In this paper, we review the research progress of diphenyl ethers isolated from marine and plant endophytic sources in recent years, including their biosynthesis, and lay the foundation for further utilization and development.

The Emergence of N. sativa L. as a Green Antifungal Agent.

Nigella sativa L. has been widely used in the Unani, Ayurveda, Chinese, and Arabic medicine systems and has a long history of medicinal and folk uses. Several phytoconstituents of the plant are reported to have excellent therapeutic properties. In-vitro and in-vivo studies have revealed that seed oil and thymoquinone have excellent inhibitory efficacy on a wide range of both pathogenic and non-pathogenic fungi. The present review aims to undertake a comprehensive and systematic evaluation of the antifungal effects of different phytochemical constituents of black cumin. An exhaustive database retrieval was conducted on PubMed, Scopus, ISI Web of Science, SciFinder, Google Scholar, and CABI to collect scientific information about the antifungal activity of N. sativa L. with 1990 to 2023 as a reference range using 'Nigella sativa,' 'Nigella oil,' 'antifungal uses,' 'dermatophytic fungi,' 'candidiasis,' 'anti-aflatoxin,' 'anti-biofilm' and 'biological activity' as the keywords. Black cumin seeds, as well as the extract of aerial parts, were found to exhibit strong antifungal activity against a wide range of fungi. Among the active compounds, thymoquinone exhibited the most potent antifungal effect. Several recent studies proved that black cumin inhibits biofilm formation and growth. The review provides an in-depth analysis of the antifungal activity of black cumin. This work emphasizes the need to expand studies on this plant to exploit its antifungal properties for biomedical applications.

Mitochondrial Dysfunction and Imeglimin: A New Ray of Hope for the Treatment of Type-2 Diabetes Mellitus.

Diabetes is a rapidly growing health challenge and epidemic in many developing countries, including India. India, being the diabetes capital of the world, has the dubious dual distinction of being the leading nations for both undernutrition and overnutrition. Diabetes prevalence has increased in both rural and urban areas, affected the younger population and increased the risk of complications and economic burden. These alarming statistics ring an alarm bell to achieve glycemic targets in the affected population in order to decrease diabetes-related morbidity and mortality. In the recent years, diabetes pathophysiology has been extended from an ominous triad through octet and dirty dozen etc. There is a new scope to target multiple pathways at the molecular level to achieve a better glycemic target and further prevent micro- and macrovascular complications. Mitochondrial dysfunction has a pivotal role in both β-cell failure and insulin resistance. Hence, targeting this molecular pathway may help with both insulin secretion and peripheral tissue sensitization to insulin. Imeglimin is the latest addition to our anti-diabetic armamentarium. As imeglimin targets, this root cause of defective energy metabolism and insulin resistance makes it a new add-on therapy in different diabetic regimes to achieve the proper glycemic targets. Its good tolerability and efficacy profiles in recent studies shows a new ray of hope in the journey to curtail diabetes-related morbidity.

"The light after the storm": Psychosocial correlates of adversarial growth among nurses in Hong Kong amid the fifth wave of the COVID-19 pandemic.

Healthcare professionals are highly susceptible to adverse psychological outcomes amid the COVID-19 pandemic due to their job duties. As the largest part of the healthcare workforce, growing attention has been paid to nurses' adjustments to the pandemic. Despite the distress, recent studies found that nurses could still experience positive changes (i.e., adversarial growth, AG) during the pandemic. Research on the general populations has indicated that individuals' stress responses, coping resources, and coping strategies are associated with their AG during the pandemic. This study examined how sociodemographic characteristics, secondary traumatic and posttraumatic stress, coping resources, and coping strategies were associated with AG among nurses in Hong Kong amid the fifth wave (i.e., the most disastrous wave) of the COVID-19 pandemic. Recruited through local nursing associations between May 24 and June 13, 2022, 209 nurses in Hong Kong completed an online questionnaire measuring the abovementioned variables. Hierarchical regression results found that those affiliating with a religion, having participated in mental health-related workshops, higher levels of secondary traumatic stress (STS), social support, job satisfaction, plus more frequent emotional processing were associated with higher AG (βs ranging from 0.15 to 0.31, ps < .01). Nurses did report AG during the fifth wave of the COVID-19 pandemic in Hong Kong. To promote AG among those nurses, future interventions should enhance nurses' understanding about the potential impact of STS on their well-being, solicit their interpersonal and work-related coping resources, plus facilitate their use of effective coping strategies. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Proportion and distribution of neurotransmitter-defined cell types in the ventral tegmental area and substantia nigra pars compacta.

Most studies on the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) have focused on dopamine neurons and their role in processes such as motivation, learning, movement, and associated disorders such as addiction. However there has been increasing attention on other VTA and SNc cell types that release GABA, glutamate, or a combination of neurotransmitters. Yet the relative distributions and proportions of neurotransmitter-defined cell types across VTA and SNc has remained unclear. Here, we used fluorescent in situ hybridization in male and female mice to label VTA and SNc neurons that expressed mRNA encoding the canonical vesicular transporters for dopamine, GABA, or glutamate: vesicular monoamine transporter (VMAT2), vesicular GABA transporter (VGAT), and vesicular glutamate transporter (VGLUT2). Within VTA, we found that no one type was particularly more abundant, instead we observed similar numbers of VMAT2+ (44%), VGAT+ (37%) and VGLUT2+ (41%) neurons. In SNc we found that a slight majority of neurons expressed VMAT2 (54%), fewer were VGAT+ (42%), and VGLUT2+ neurons were least abundant (16%). Moreover, 20% of VTA neurons and 10% of SNc neurons expressed more than one vesicular transporter, including 45% of VGLUT2+ neurons. We also assessed within VTA and SNc subregions and found remarkable heterogeneity in cell-type composition. And by quantifying density across both anterior-posterior and medial-lateral axes we generated heatmaps to visualize the distribution of each cell type. Our data complement recent single-cell RNAseq studies and support a more diverse landscape of neurotransmitter-defined cell types in VTA and SNc than is typically appreciated.