Recent Studies Research Articles

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.

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.

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).

Feedback inhibition by a descending GABAergic neuron regulates timing of escape behavior in Drosophila larvae.

Escape behaviors help animals avoid harm from predators and other threats in the environment. Successful escape relies on integrating information from multiple stimulus modalities (of external or internal origin) to compute trajectories toward safe locations, choose between actions that satisfy competing motivations, and execute other strategies that ensure survival. To this end, escape behaviors must be adaptive. When a Drosophila melanogaster larva encounters a noxious stimulus, such as the focal pressure a parasitic wasp applies to the larval cuticle via its ovipositor, it initiates a characteristic escape response. The escape sequence consists of an initial abrupt bending, lateral rolling, and finally rapid crawling. Previous work has shown that the detection of noxious stimuli primarily relies on class IV multi-dendritic arborization neurons (Class IV neurons) located beneath the body wall, and more recent studies have identified several important components in the nociceptive neural circuitry involved in rolling. However, the neural mechanisms that underlie the rolling-escape sequence remain unclear. Here, we present both functional and anatomical evidence suggesting that bilateral descending neurons within the subesophageal zone of D. melanogaster larva play a crucial role in regulating the termination of rolling and subsequent transition to escape crawling. We demonstrate that these descending neurons (designated SeIN128) are inhibitory and receive inputs from a second-order interneuron upstream (Basin-2) and an ascending neuron downstream of Basin-2 (A00c). Together with optogenetic experiments showing that co-activation of SeIN128 neurons and Basin-2 influence the temporal dynamics of rolling, our findings collectively suggest that the ensemble of SeIN128, Basin-2, and A00c neurons forms a GABAergic feedback loop onto Basin-2, which inhibits rolling and thereby facilitates the shift to escape crawling.

Recent Research on the Identification, Assessment, and Response to Fraud Risks: Implications for Audit Practice and Topics for Future Research

SYNOPSIS The financial statement auditor’s identification of fraud risk factors, their assessment of fraud risk, and their fraud risk responses are key to the auditor’s consideration of fraud and fraud detection. Given that the last review of research related to the search for fraud during the audit occurred nearly a decade ago, we provide a summary of recent academic research to update and inform practitioners, researchers, standard setters, regulators, and other stakeholders in the financial reporting process. We categorize and summarize findings from recent academic studies that focus on the auditor’s identification, assessment, and responses to fraud risks. Implications for practice are presented for each of these areas, along with topics and questions for future research. JEL Classifications: M40; M41; M42; M48.

Transcriptomic profiling of Schlemm's canal cells reveals a lymphatic-biased identity and three major cell states.

Schlemm's canal is a critical ocular drainage structure that maintains intraocular pressure with important consequences for glaucoma. Despite this, Schlemm's canal has been relatively understudied with the molecular process that mediate its function, maintain its health, or that are compromised in glaucoma needing much deeper characterization. This study is important as it provides the most comprehensive molecular characterization of Schlemm's canal cells to date providing a wealth of molecular details. In addition to highlighting important biological pathways, this information will guide studies to develop new treatments against glaucoma.

Synthesis of N1-caffeoyl-N10-dihydrocaffeoylspermidine (Scotanamine D)

Abstract: N1-caffeoyl-N10-dihydrocaffeoylspermidine (Scotanamine D), a spermidine alkaloid isolated from various plants, is a medicinally valuable natural product. Recent studies have pointed out several health benefits of this compound. However, its synthetic procedures are still not described in the literature. We report the synthesis of this compound following two different schemes comprising multiple steps with excellent overall yields, which are 57% and 81%, respectively. These two synthetic schemes, which use commercially available and cheaper starting materials, can facilitate the large-scale manufacturing of Scotanamine D.

Bayesian Dictionary Learning on Robust Tubal Transformed Tensor Factorization.

The recent study on tensor singular value decomposition (t-SVD) that performs the Fourier transform on the tubes of a third-order tensor has gained promising performance on multidimensional data recovery problems. However, such a fixed transformation, e.g., discrete Fourier transform and discrete cosine transform, lacks being self-adapted to the change of different datasets, and thus, it is not flexible enough to exploit the low-rank and sparse property of the variety of multidimensional datasets. In this article, we consider a tube as an atom of a third-order tensor and construct a data-driven learning dictionary from the observed noisy data along the tubes of the given tensor. Then, a Bayesian dictionary learning (DL) model with tensor tubal transformed factorization, aiming to identify the underlying low-tubal-rank structure of the tensor effectively via the data-adaptive dictionary, is developed to solve the tensor robust principal component analysis (TRPCA) problem. With the defined pagewise tensor operators, a variational Bayesian DL algorithm is established and updates the posterior distributions instantaneously along the third dimension to solve the TPRCA. Extensive experiments on real-world applications, such as color image and hyperspectral image denoising and background/foreground separation problems, demonstrate both effectiveness and efficiency of the proposed approach in terms of various standard metrics.

The Therapeutic Potential and Molecular Mechanisms Underlying the Neuroprotective Effects of Sativex® - A Cannabis-derived Spray.

Sativex is a cannabis-based medicine that comes in the form of an oromucosal spray. It contains equal amounts of Δ9-tetrahydrocannabinol and cannabidiol, two compounds derived from cannabis plants. Sativex has been shown to have positive effects on symptoms of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and sleep disorders. It also has analgesic, antiinflammatory, antitumoral, and neuroprotective properties, which make it a potential treatment option for other neurological disorders. The article reviews the results of recent preclinical and clinical studies that support the therapeutic potential of Sativex and the molecular mechanisms behind its neuroprotective benefits in various neurological disorders. The article also discusses the possible advantages and disadvantages of using Sativex as a neurotherapeutic agent, such as its safety, efficacy, availability, and legal status.

The role of HSP40 in cancer: Recent advances.

Heat shock proteins (HSPs) are a family of proteins involved in protein folding and maturation that are expressed by cells in response to stressors including heat shock. Recent studies have demonstrated that HSPs play major roles in carcinogenesis by regulating angiogenesis, cell proliferation, migration, invasion, metastasis, apoptosis, as well as therapy resistance to certain anticancer drugs. Despite being the largest and most diverse subgroup of the HSP family, HSP40 (DNAJ) is an understudied family of co-chaperones. HSP40 family members are also known to be involved in various types of cancers. In this article, we review the involvement of human HSP40 family members in various aspects of cancer biology. In addition, we highlight the possible potential of HSP40 as a tumor biomarker or drug target for improving the prognosis and treatment of cancer patients in the future.

A Glove-Based Virtual Hand Rehabilitation System for Patients With Post-Traumatic Hand Injuries.

Recent studies have shown that virtual gamified therapy can be a potential adjunct to conventional orthopedic rehabilitation. However, the off-the-shelf gaming consoles used for virtual rehabilitation pose several practical challenges in deploying them in clinical settings. In this article, we present the design of a portable glove-based virtual hand rehabilitation system (RehabRelive Glove) that can be used at both clinics and homes for physiotherapy. We also evaluate the system's efficacy on patients with post-traumatic hand injuries. Thirty patients were randomly categorized into groups A (virtual rehabilitation) and B (conventional physiotherapy). Both groups received fifteen 25-minute sessions of respective therapy over three weeks. The wrist and finger joints' range of motion (ROM) and grip strength were measured every seven sessions to compare the efficacy. Group A showed about 1.5 times greater improvement in flexion/extension ROM of the wrist compared to Group B. While both groups improved finger ROM and grip strength with time, no significant difference was observed between the groups. The results suggest that the proposed virtual rehabilitation system effectively enables patients with hand injuries to recover ROM faster.

SPD Manifold Deep Metric Learning for Image Set Classification.

By characterizing each image set as a nonsingular covariance matrix on the symmetric positive definite (SPD) manifold, the approaches of visual content classification with image sets have made impressive progress. However, the key challenge of unhelpfully large intraclass variability and interclass similarity of representations remains open to date. Although, several recent studies have mitigated the two problems by jointly learning the embedding mapping and the similarity metric on the original SPD manifold, their inherent shallow and linear feature transformation mechanism are not powerful enough to capture useful geometric features, especially in complex scenarios. To this end, this article explores a novel approach, termed SPD manifold deep metric learning (SMDML), for image set classification. Specifically, SMDML first selects a prevailing SPD manifold neural network (SPDNet) as the backbone (encoder) to derive an SPD matrix nonlinear representation. To counteract the degradation of structural information during multistage feature embedding, we construct a Riemannian decoder at the end of the encoder, trained by a reconstruction error term (RT), to induce the generated low-dimensional feature manifold of the hidden layer to capture the pivotal information about the visual data describing the imaged scene. We demonstrate through theory and experiments that it is feasible to replace the Riemannian metric with Euclidean distance in RT. Then, the ReCov layer is introduced into the established Riemannian network to regularize the local statistical information within each input feature matrix, which enhances the effectiveness of the learning process. The theoretical analysis of the activation function used in the ReCov layer in terms of continuity and conditions for generating positive definite matrices is beneficial for network design. Inspired by the fact that the single cross-entropy loss used for training is unable to effectively parse the geometric distribution of the deep representations, we finally endow the suggested model with a novel metric learning regularization term. By explicitly incorporating the encoding and processing of the data variations into the network learning process, this term can not only derive a powerful Riemannian representation but also train an effective classifier. The experimental results show the superiority of the proposed approach on three typical visual classification tasks.