In the period from 2013 to 2022, 2462 publications dealing with TRPV1 and pain were identified. These publications were authored by 12005 researchers from 2304 institutions in 68 countries/regions, and published across 686 journals, with a cumulative citation count of 48723. The volume of publications has experienced significant growth during the previous ten years. U.S. and Chinese publications accounted for a significant portion of the research; Seoul National University displayed the most activity amongst institutions; Tominaga M. had the largest number of individual publications, with Caterina MJ demonstrating the highest co-citation count; The journal Pain was the most prevalent source; The Julius D. work received the highest number of citations; Neuropathic, inflammatory, visceral, and migraine pain were the most prominent forms of pain investigated. The pain-related TRPV1 process was a key target of research efforts.
The research directions of TRPV1 in the pain field, as ascertained by bibliometric analysis over the last ten years, were comprehensively surveyed in this study. The study's outcomes could reveal the prominent trends and critical areas within this field, offering important information to clinicians regarding pain treatment.
A review of major research directions in TRPV1 and pain, covering the last decade, was performed using bibliometric methodologies in this study. Unveiling research patterns and key areas of interest within the field, the results could offer beneficial guidance for pain treatment applications.
A global affliction, cadmium (Cd) toxicity affects millions of individuals. Humans primarily absorb cadmium through the consumption of tainted food and water, through cigarette smoking, and through industrial applications. selleckchem The proximal tubular epithelial cells of the kidney are the principal cells affected by Cd toxicity. The impairment of tubular reabsorption results from cadmium's effect on proximal tubule cells. Though the significant long-term sequelae of Cd exposure are well documented, the molecular mechanisms responsible for Cd toxicity remain poorly understood, and no specific therapies are available to mitigate the effects of Cd exposure. We overview recent work in this review, linking cadmium-mediated harm to alterations in epigenetic processes, such as DNA methylation and changes in histone modifications, including methylation and acetylation. Unveiling the intricate links between cadmium exposure and epigenetic alterations will enhance our knowledge of cadmium's diverse impact on cellular processes, potentially fostering the development of novel, mechanism-based therapies for this.
Significant progress in precision medicine is being achieved through the potent therapeutic applications of antisense oligonucleotide (ASO) therapies. An emerging class of antisense drugs is now credited with the early successes in treating certain genetic diseases. Over a span of two decades, the US Food and Drug Administration (FDA) has approved a substantial number of ASO medications, primarily targeting rare diseases to achieve optimal therapeutic outcomes. A paramount concern regarding the therapeutic value of ASO drugs is, undoubtedly, their safety profile. Because of the considerable and pressing requests from patients and healthcare practitioners for medications for incurable diseases, various ASO drugs have been approved. However, a comprehensive understanding of the mechanisms pertaining to adverse drug reactions (ADRs) and the harmful effects of antisense oligonucleotides (ASOs) has not been definitively established. medical testing A drug's adverse reaction profile (ADR) is distinct, while only a small number of ADRs affect multiple drugs in a class. The potential for nephrotoxicity represents a crucial hurdle in the clinical application of drug candidates, spanning small molecule and ASO-based medications. The nephrotoxicity of ASO drugs, including possible mechanisms of action and future research recommendations, is the subject of this article.
Physical and chemical stimuli trigger the polymodal non-selective cation channel known as TRPA1, a transient receptor potential ankyrin 1. prostatic biopsy puncture In diverse species, TRPA1's association with key physiological processes leads to distinct levels of evolutionary involvement. TRPA1, a multi-modal receptor in various animal species, is activated by irritating chemicals, cold, heat, and mechanical sensations. Many studies have validated the diverse functions of TRPA1, but the scientific community remains divided on its temperature-sensing capabilities. Despite its broad distribution throughout both invertebrates and vertebrates, and its essential role in temperature detection, the function of TRPA1 thermosensation and its molecular temperature sensitivity exhibit species-specific attributes. This review encompasses the temperature-sensing function of TRPA1 orthologs from molecular, cellular, and behavioral standpoints.
CRISPR-Cas, a highly adaptable genome editing system, has experienced broad application across both basic research and translational medicine. Engineered from their bacterial origins, endonucleases have evolved into a potent collection of genome-editing tools, facilitating the precise introduction of frameshift mutations or base changes at specific locations within the genome. Beginning in 2016 with the initial first-in-human CRISPR-Cas trial, 57 clinical trials have evaluated this technology in cell therapies, including 38 trials for engineered CAR-T and TCR-T cells for cancer, 15 trials for engineered hematopoietic stem cells in treating hemoglobinopathies, leukemia, and AIDS, and 4 trials for engineered iPSCs in the treatment of diabetes and cancer. Current CRISPR advancements and their practical application in cell therapies are explored in this analysis.
Forebrain cholinergic input substantially originates from cholinergic neurons within the basal forebrain, impacting functions such as sensory processing, memory, and attention, and placing them at risk for Alzheimer's disease. A recent study has shown that cholinergic neurons can be classified into two distinct subtypes: calbindin D28K positive cells (D28K+) and calbindin D28K negative cells (D28K-). Yet, the identity of the cholinergic subpopulations uniquely vulnerable to Alzheimer's disease (AD), and the molecular mechanisms behind this selective degradation, are not yet understood. We report here the degeneration of D28K+ neurons, found selectively, and its subsequent induction of anxiety-like behaviors in the initial stages of AD. Removing NRADD selectively from particular neuronal types effectively mitigates the degeneration of D28K+ neurons, conversely, introducing exogenous NRADD genetically results in neuronal loss in D28K- neurons. Through a gain- and loss-of-function study, researchers have uncovered a subtype-specific degeneration of cholinergic neurons in Alzheimer's disease progression, indicating a novel molecular target for AD therapy.
Cardiac injury leaves the heart unable to regenerate, due to the limited regenerative capacity of adult cardiomyocytes. Direct cardiac reprogramming's potential lies in converting scar-forming cardiac fibroblasts into functional induced-cardiomyocytes, facilitating the restoration of heart structure and function. Significant improvements in iCM reprogramming are attributable to the combined use of genetic and epigenetic regulators, small molecules, and sophisticated delivery strategies. Recent investigations into the heterogeneity and reprogramming pathways of induced cells (iCMs) provided insight into novel mechanisms, examining the process at a single-cell resolution. Recent research on iCM reprogramming, in particular, multi-omics analysis (transcriptomics, epigenomics, and proteomics), is reviewed to explore the cellular and molecular underpinnings of cell fate change. Furthermore, we emphasize the future potential of multi-omics strategies to unravel the intricacies of iCMs conversion for clinical translation.
Currently available prosthetic hands possess the capability of actuating anywhere from five to 30 degrees of freedom (DOF). Nevertheless, the manipulation of these devices is unfortunately not easily understood or handled. To approach this issue effectively, we advocate for a direct extraction of finger commands from the neuromuscular system. In two individuals with transradial amputations, bipolar electrodes were implanted into their residual innervated muscles, coupled with regenerative peripheral nerve interfaces (RPNIs). Large signal amplitudes were a hallmark of the local electromyography recordings made by the implanted electrodes. Within the confines of single-day experiments, participants directed a virtual prosthetic hand in real-time with the assistance of a high-speed movement classifier. Participants demonstrated a 947% average success rate in transitioning between ten pseudo-randomly cued individual finger and wrist postures, with a trial latency averaging 255 milliseconds. Reducing the posture set to five elements resulted in a remarkable improvement, achieving 100% success and a 135 ms trial latency. The weight of the prosthesis was stably supported across the spectrum of static arm positions, which were not previously trained. Participants utilized the high-speed classifier to alternate between robotic prosthetic grips, subsequently completing a functional performance evaluation. These results showcase the effectiveness of pattern recognition systems in controlling prosthetic grasps with the speed and precision offered by intramuscular electrodes and RPNIs.
A micro-mapping survey of terrestrial gamma radiation dose (TGRD) at a meter resolution, carried out around four urban homes in Miri City, recorded dose rates varying between 70 and 150 nGy/hour. Properties' tiled floors and walls show disparities, noticeably affecting TGRD, which peaks in areas like kitchens, bathrooms, and toilets. Considering a single indoor annual effective dose (AED) value could lead to an underestimation of the true exposure level, possibly by as much as 30%. The projected AED level in homes of this sort in Miri is improbable to surpass 0.08 mSv, aligning precisely with recommended limits.