-
PLoS Neglected Tropical Diseases Apr 2024Cutaneous leishmaniasis (CL) is characterized by potentially disfiguring skin ulcers carrying significant social stigma. To mitigate systemic drug exposure and reduce...
BACKGROUND
Cutaneous leishmaniasis (CL) is characterized by potentially disfiguring skin ulcers carrying significant social stigma. To mitigate systemic drug exposure and reduce the toxicity from available treatments, studies addressing new local therapeutic strategies using available medications are coming up. This review systematically compiles preclinical and clinical data on the efficacy of amphotericin B (AmB) administered locally for cutaneous leishmaniasis.
METHODOLOGY
Structured searches were conducted in major databases. Clinical studies reporting cure rates and preclinical studies presenting any efficacy outcome were included. Exclusion criteria comprised nonoriginal studies, in vitro investigations, studies with fewer than 10 treated patients, and those evaluating AmB in combination with other antileishmanial drug components.
PRINCIPAL FINDINGS
A total of 21 studies were identified, encompassing 16 preclinical and five clinical studies. Preclinical assessments generally involved the topical use of commercial AmB formulations, often in conjunction with carriers or controlled release systems. However, the variation in the treatment schedules hindered direct comparisons. In clinical studies, topical AmB achieved a pooled cure rate of 45.6% [CI: 27.5-64.8%; I2 = 79.7; p = 0.002), while intralesional (IL) administration resulted in a 69.8% cure rate [CI: 52.3-82.9%; I2 = 63.9; p = 0.06). In the direct comparison available, no significant difference was noted between AmB-IL and meglumine antimoniate-IL administration (OR:1.7; CI:0.34-9.15, I2 = 79.1; p = 0.00), however a very low certainty of evidence was verified.
CONCLUSIONS
Different AmB formulations and administration routes have been explored in preclinical and clinical studies. Developing therapeutic technologies is evident. Current findings might be interpreted as a favorable proof of concept for the local AmB administration which makes this intervention eligible to be explored in future well-designed studies towards less toxic treatments for leishmaniasis.
Topics: Leishmaniasis, Cutaneous; Amphotericin B; Humans; Antiprotozoal Agents; Administration, Topical; Treatment Outcome
PubMed: 38626196
DOI: 10.1371/journal.pntd.0012127 -
Biology Methods & Protocols 2024Pyrimethamine (PYR), a STAT3 inhibitor, has been shown to reduce tumour burden in mouse cancer models. It is unclear how much of a reduction occurred or whether the PYR... (Review)
Review
Pyrimethamine (PYR), a STAT3 inhibitor, has been shown to reduce tumour burden in mouse cancer models. It is unclear how much of a reduction occurred or whether the PYR dosages and route of administration used in mice were consistent with the FDA's recommendations for drug repurposing. Search engines such as ScienceDirect, PubMed/MEDLINE, and other databases, including Google Scholar, were thoroughly searched, as was the reference list. The systematic review includes fourteen (14) articles. The risk of bias (RoB) was assessed using SYRCLE's guidelines. Due to the heterogeneity of the data, no meta-analysis was performed. According to the RoB assessment, 13/14 studies fall into the moderate RoB category, with one study classified as high RoB. None adhered to the ARRIVE guideline for transparent research reporting. Oral (FDA-recommended) and non-oral routes of PYR administration were used in mice, with several studies reporting very high PYR dosages that could lead to myelosuppression, while oral PYR dosages of 30 mg/kg or less are considered safe. Direct human equivalent dose translation is probably not the best strategy for comparing whether the used PYR dosages in mice are in line with FDA-approved strength because pharmacokinetic profiles, particularly PYR's half-life (t), between humans (t = 96 h) and mice (t = 6 h), must also be considered. Based on the presence of appropriate control and treatment groups, as well as the presence of appropriate clinically proven chemotherapy drug(s) for comparison purposes, only one study (1/14) involving liver cancer can be directed into a clinical trial. Furthermore, oesophageal cancer too can be directed into clinical trials, where the indirect effect of PYR on the NRF2 gene may suppress oesophageal cancer in patients, but this must be done with caution because PYR is an investigational drug for oesophageal cancer, and combining it with proven chemotherapy drug(s) is recommended.
PubMed: 38618181
DOI: 10.1093/biomethods/bpae021 -
Disease Models & Mechanisms May 2024Preclinical and clinical studies on the administration of bone marrow-derived cells to restore perfusion show conflicting results. We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
Preclinical and clinical studies on the administration of bone marrow-derived cells to restore perfusion show conflicting results. We conducted a systematic review and meta-analysis on preclinical studies to assess the efficacy of bone marrow-derived cells in the hind limb ischemia model and identify possible determinants of therapeutic efficacy. In vivo animal studies were identified using a systematic search in PubMed and EMBASE on 10 January 2022. 85 studies were included for systematic review and meta-analysis. Study characteristics and outcome data on relative perfusion were extracted. The pooled mean difference was estimated using a random effects model. Risk of bias was assessed for all included studies. We found a significant increase in perfusion in the affected limb after administration of bone marrow-derived cells compared to that in the control groups. However, there was a high heterogeneity between studies, which could not be explained. There was a high degree of incomplete reporting across studies. We therefore conclude that the current quality of preclinical research is insufficient (low certainty level as per GRADE assessment) to identify specific factors that might improve human clinical trials.
Topics: Animals; Hindlimb; Ischemia; Bone Marrow Cells; Perfusion; Bone Marrow Transplantation; Humans; Publication Bias; Cell- and Tissue-Based Therapy
PubMed: 38616715
DOI: 10.1242/dmm.050632 -
Medicina Oral, Patologia Oral Y Cirugia... Apr 2024Apicomarginal lesions affect the root apex and root surface concurrently and reduce the success rate in periapical surgery. The purpose of this systematic review was to...
BACKGROUND
Apicomarginal lesions affect the root apex and root surface concurrently and reduce the success rate in periapical surgery. The purpose of this systematic review was to analyze the published literature on the surgical treatment of apicomarginal lesions in periapical surgery.
MATERIAL AND METHODS
A systematic review was conducted on PRISMA statement. Three data bases (PubMed-Medline, Scopus, and Embase) were searched up to March 2023. The inclusion criteria for this systematic review encompass studies pertaining to apicomarginal lesions and their surgical treatment, both preclinical and clinical in nature (including randomized trials, prospective, and retrospective observational trials), without any language or time limitations. Exclusion criteria encompass studies with duplicated population data, no description of the surgical treatment or regenerative material. Different tools for the assessment of bias were applied for each study design Results: A total of 155 articles were searched and 10 were included. Studies on teeth with apicomarginal lesions undergoing periapical surgery showed a high success rate when regenerative techniques were used, resulting in reduced probing depth, increased bone formation on the root surface, increased root cementum formation, and reduced healing by junctional epithelium. Guided tissue regeneration, platelet-rich plasma or fibrin, and enamel matrix derivatives have emerged as alternative treatments offering favorable outcomes.
CONCLUSIONS
The use of regenerative materials in periapical surgery could improve the prognosis of apicomarginal lesions. Future research in this field should aim to standardize classification and healing criteria to enhance comparability across studies and provide more conclusive evidence for optimal treatment approaches.
PubMed: 38615249
DOI: 10.4317/medoral.26405 -
International Journal of Molecular... Apr 2024Melatonin's cytoprotective properties may have therapeutic implications in treating ocular diseases like glaucoma and age-related macular degeneration. Literature data... (Review)
Review
Melatonin's cytoprotective properties may have therapeutic implications in treating ocular diseases like glaucoma and age-related macular degeneration. Literature data suggest that melatonin could potentially protect ocular tissues by decreasing the production of free radicals and pro-inflammatory mediators. This study aims to summarize the screened articles on melatonin's clinical, pharmacological, and formulation evaluation in treating ocular disorders. The identification of relevant studies on the topic in focus was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. The studies were searched in the following databases and web search engines: Pubmed, Scopus, Science Direct, Web of Science, Reaxys, Google Scholar, Google Patents, Espacenet, and Patentscope. The search time interval was 2013-2023, with the following keywords: melatonin AND ocular OR ophthalmic AND formulation OR insert AND disease. Our key conclusion was that using melatonin-loaded nano-delivery systems enabled the improved permeation of the molecule into intraocular tissues and assured controlled release profiles. Although preclinical studies have demonstrated the efficacy of developed formulations, a considerable gap has been observed in the clinical translation of the results. To overcome this failure, revising the preclinical experimental phase might be useful by selecting endpoints close to clinical ones.
Topics: Humans; Melatonin; Eye; Glaucoma; Face; Databases, Factual
PubMed: 38612812
DOI: 10.3390/ijms25073999 -
Communications Medicine Apr 2024The field of Artificial Intelligence (AI) holds transformative potential in medicine. However, the lack of universal reporting guidelines poses challenges in ensuring...
BACKGROUND
The field of Artificial Intelligence (AI) holds transformative potential in medicine. However, the lack of universal reporting guidelines poses challenges in ensuring the validity and reproducibility of published research studies in this field.
METHODS
Based on a systematic review of academic publications and reporting standards demanded by both international consortia and regulatory stakeholders as well as leading journals in the fields of medicine and medical informatics, 26 reporting guidelines published between 2009 and 2023 were included in this analysis. Guidelines were stratified by breadth (general or specific to medical fields), underlying consensus quality, and target research phase (preclinical, translational, clinical) and subsequently analyzed regarding the overlap and variations in guideline items.
RESULTS
AI reporting guidelines for medical research vary with respect to the quality of the underlying consensus process, breadth, and target research phase. Some guideline items such as reporting of study design and model performance recur across guidelines, whereas other items are specific to particular fields and research stages.
CONCLUSIONS
Our analysis highlights the importance of reporting guidelines in clinical AI research and underscores the need for common standards that address the identified variations and gaps in current guidelines. Overall, this comprehensive overview could help researchers and public stakeholders reinforce quality standards for increased reliability, reproducibility, clinical validity, and public trust in AI research in healthcare. This could facilitate the safe, effective, and ethical translation of AI methods into clinical applications that will ultimately improve patient outcomes.
PubMed: 38605106
DOI: 10.1038/s43856-024-00492-0 -
Translational Psychiatry Apr 2024Deep brain stimulation (DBS) modulates local and widespread connectivity in dysfunctional networks. Positive results are observed in several patient populations;...
Deep brain stimulation (DBS) modulates local and widespread connectivity in dysfunctional networks. Positive results are observed in several patient populations; however, the precise mechanisms underlying treatment remain unknown. Translational DBS studies aim to answer these questions and provide knowledge for advancing the field. Here, we systematically review the literature on DBS studies involving models of neurological, developmental and neuropsychiatric disorders to provide a synthesis of the current scientific landscape surrounding this topic. A systematic analysis of the literature was performed following PRISMA guidelines. 407 original articles were included. Data extraction focused on study characteristics, including stimulation protocol, behavioural outcomes, and mechanisms of action. The number of articles published increased over the years, including 16 rat models and 13 mouse models of transgenic or healthy animals exposed to external factors to induce symptoms. Most studies targeted telencephalic structures with varying stimulation settings. Positive behavioural outcomes were reported in 85.8% of the included studies. In models of psychiatric and neurodevelopmental disorders, DBS-induced effects were associated with changes in monoamines and neuronal activity along the mesocorticolimbic circuit. For movement disorders, DBS improves symptoms via modulation of the striatal dopaminergic system. In dementia and epilepsy models, changes to cellular and molecular aspects of the hippocampus were shown to underlie symptom improvement. Despite limitations in translating findings from preclinical to clinical settings, rodent studies have contributed substantially to our current knowledge of the pathophysiology of disease and DBS mechanisms. Direct inhibition/excitation of neural activity, whereby DBS modulates pathological oscillatory activity within brain networks, is among the major theories of its mechanism. However, there remain fundamental questions on mechanisms, optimal targets and parameters that need to be better understood to improve this therapy and provide more individualized treatment according to the patient's predominant symptoms.
Topics: Mice; Humans; Rats; Animals; Deep Brain Stimulation; Rodentia; Brain; Epilepsy; Hippocampus
PubMed: 38605027
DOI: 10.1038/s41398-023-02727-5 -
Current HIV/AIDS Reports Jun 2024Cannabis may have beneficial anti-inflammatory effects in people with HIV (PWH); however, given this population's high burden of persisting neurocognitive impairment... (Review)
Review
PURPOSE OF REVIEW
Cannabis may have beneficial anti-inflammatory effects in people with HIV (PWH); however, given this population's high burden of persisting neurocognitive impairment (NCI), clinicians are concerned they may be particularly vulnerable to the deleterious effects of cannabis on cognition. Here, we present a systematic scoping review of clinical and preclinical studies evaluating the effects of cannabinoid exposure on cognition in HIV.
RECENT FINDINGS
Results revealed little evidence to support a harmful impact of cannabis use on cognition in HIV, with few eligible preclinical data existing. Furthermore, the beneficial/harmful effects of cannabis use observed on cognition were function-dependent and confounded by several factors (e.g., age, frequency of use). Results are discussed alongside potential mechanisms of cannabis effects on cognition in HIV (e.g., anti-inflammatory), and considerations are outlined for screening PWH that may benefit from cannabis interventions. We further highlight the value of accelerating research discoveries in this area by utilizing translatable cross-species tasks to facilitate comparisons across human and animal work.
Topics: Humans; HIV Infections; Cognition; Cannabis; Cannabinoids; Animals; Cognitive Dysfunction; Marijuana Use
PubMed: 38602558
DOI: 10.1007/s11904-024-00698-w -
Frontiers in Aging Neuroscience 2024With the aging of the population, the health of the elderly has become increasingly important. Postoperative cognitive dysfunction (POCD) is a common neurological...
With the aging of the population, the health of the elderly has become increasingly important. Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients following general anesthesia or surgery. It is characterized by cognitive decline that may persist for weeks, months, or even longer. Electroacupuncture (EA), a novel therapy that combines physical nerve stimulation with acupuncture treatment from traditional Chinese medicine, holds potential as a therapeutic intervention for preventing and treating POCD, particularly in elderly patients. Although the beneficial effects of EA on POCD have been explored in preclinical and clinical studies, the reliability of EA is limited by methodological shortcomings, and the underlying mechanisms remain largely unexplored. Therefore, we have synthesized existing evidence and proposed potential biological mechanisms underlying the effects of EA on neuroinflammation, oxidative stress, autophagy, the microbiota-gut-brain axis, and epigenetic modification. This review summarizes recent advances in EA and POCD, provides a theoretical foundation, explores potential molecular mechanisms for the prevention and treatment of POCD, and offers a basis for conducting relevant clinical trials.
PubMed: 38596595
DOI: 10.3389/fnagi.2024.1384075 -
Neural Regeneration Research Dec 2024Regenerative approaches towards neuronal loss following traumatic brain or spinal cord injury have long been considered a dogma in neuroscience and remain a cutting-edge...
Regenerative approaches towards neuronal loss following traumatic brain or spinal cord injury have long been considered a dogma in neuroscience and remain a cutting-edge area of research. This is reflected in a large disparity between the number of studies investigating primary and secondary injury as therapeutic targets in spinal cord and traumatic brain injuries. Significant advances in biotechnology may have the potential to reshape the current state-of-the-art and bring focus to primary injury neurotrauma research. Recent studies using neural-glial factor/antigen 2 (NG2) cells indicate that they may differentiate into neurons even in the developed brain. As these cells show great potential to play a regenerative role, studies have been conducted to test various manipulations in neurotrauma models aimed at eliciting a neurogenic response from them. In the present study, we systematically reviewed the experimental protocols and findings described in the scientific literature, which were peer-reviewed original research articles (1) describing preclinical experimental studies, (2) investigating NG2 cells, (3) associated with neurogenesis and neurotrauma, and (4) in vitro and/or in vivo, available in PubMed/MEDLINE, Web of Science or SCOPUS, from 1998 to 2022. Here, we have reviewed a total of 1504 papers, and summarized findings that ultimately suggest that NG2 cells possess an inducible neurogenic potential in animal models and in vitro. We also discriminate findings of NG2 neurogenesis promoted by different pharmacological and genetic approaches over functional and biochemical outcomes of traumatic brain injury and spinal cord injury models, and provide mounting evidence for the potential benefits of manipulated NG2 cell ex vivo transplantation in primary injury treatment. These findings indicate the feasibility of NG2 cell neurogenesis strategies and add new players in the development of therapeutic alternatives for neurotrauma.
PubMed: 38595286
DOI: 10.4103/NRR.NRR-D-23-01031