Advances in Antifungal Drug Development: An Up-To-Date Mini Review.
Ontology highlight
ABSTRACT:
SUBMITTER: Bouz G
PROVIDER: S-EPMC8706862 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The 2-haloacid dehalogenases (EC 3.8.1.X) are industrially important enzymes that catalyze the cleavage of carbon-halogen bonds in 2-haloalkanoic acids, releasing halogen ions and producing corresponding 2-hydroxyl acids. These enzymes are of particular interest in environmental remediation and environmentally friendly synthesis of optically pure chiral compounds due to their ability to degrade a wide range of halogenated compounds with astonishing efficiency for enantiomer resolution. The 2-haloacid dehalogenases have been extensively studied with regard to their biochemical characterization, protein crystal structures, and catalytic mechanisms. This paper comprehensively reviews the source of isolation, classification, protein structures, reaction mechanisms, biochemical properties, and application of 2-haloacid dehalogenases; current trends and avenues for further development have also been included.
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Project description:In the last decades, the treatment of primary and secondary bone tumors has faced a slow-down in its development, being mainly based on chemotherapy, radiotherapy, and surgical interventions. However, these conventional therapeutic strategies present a series of disadvantages (e.g., multidrug resistance, tumor recurrence, severe side effects, formation of large bone defects), which limit their application and efficacy. In recent years, these procedures were combined with several adjuvant therapies, with different degrees of success. To overcome the drawbacks of current therapies and improve treatment outcomes, other strategies started being investigated, like carrier-mediated drug delivery, bone substitutes for repairing bone defects, and multifunctional scaffolds with bone tissue regeneration and antitumor properties. Thus, this paper aims to present the types of bone tumors and their current treatment approaches, further focusing on the recent advances in new therapeutic alternatives.
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Project description:Prostate cancer (PCa) is the most common worldwide diagnosed malignancy in male population. The diagnosis, the identification of aggressive disease, and the post-treatment follow-up needs a more comprehensive and holistic approach. Radiomics is the extraction and interpretation of images phenotypes in a quantitative manner. Radiomics may give an advantage through advancements in imaging modalities and through the potential power of artificial intelligence techniques by translating those features into clinical outcome prediction. This article gives an overview on the current evidence of methodology and reviews the available literature on radiomics in PCa patients, highlighting its potential for personalized treatment and future applications.
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Project description:Neuroprotective strategies that limit secondary tissue loss and/or improve functional outcomes have been identified in multiple animal models of ischemic, hemorrhagic, traumatic and nontraumatic cerebral lesions. However, use of these potential interventions in human randomized controlled studies has generally given disappointing results. In this paper, we summarize the current status in terms of neuroprotective strategies, both in the immediate and later stages of acute brain injury in adults. We also review potential new strategies and highlight areas for future research.
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Project description:Multiple sclerosis (MS) is a prevalent inflammatory disease of the central nervous system that often leads to disability in young adults. Treatment options are limited and often only partly effective. The disease is likely caused by a complex interaction between multiple genes and environmental factors, leading to inflammatory-mediated central nervous system deterioration. A series of genomic studies have confirmed a central role for the immune system in the development of MS, including genetic association studies that have now dramatically expanded the roster of MS susceptibility genes beyond the longstanding human leukocyte antigen (HLA) association in MS first identified nearly 40 years ago. Advances in technology together with novel models for collaboration across research groups have enabled the discovery of more than 50 non-HLA genetic risk factors associated with MS. However, with a large proportion of the disease heritability still unaccounted for, current studies are now geared towards identification of causal alleles, associated pathways, epigenetic mechanisms, and gene-environment interactions. This article reviews recent efforts in addressing the genetics of MS and the challenges posed by an ever increasing amount of analyzable data, which is spearheading development of novel statistical methods necessary to cope with such complexity.
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Project description:Breast cancer is the most common cancer worldwide. The occurrence of breast cancer is associated with many risk factors, including genetic and hereditary predisposition. Breast cancers are highly heterogeneous. Treatment strategies for breast cancer vary by molecular features, including activation of human epidermal growth factor receptor 2 (HER2), hormonal receptors (estrogen receptor [ER] and progesterone receptor [PR]), gene mutations (e.g., mutations of breast cancer 1/2 [BRCA1/2] and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [PIK3CA]) and markers of the immune microenvironment (e.g., tumor-infiltrating lymphocyte [TIL] and programmed death-ligand 1 [PD-L1]). Early-stage breast cancer is considered curable, for which local-regional therapies (surgery and radiotherapy) are the cornerstone, with systemic therapy given before or after surgery when necessary. Preoperative or neoadjuvant therapy, including targeted drugs or immune checkpoint inhibitors, has become the standard of care for most early-stage HER2-positive and triple-negative breast cancer, followed by risk-adapted post-surgical strategies. For ER-positive early breast cancer, endocrine therapy for 5-10 years is essential. Advanced breast cancer with distant metastases is currently considered incurable. Systemic therapies in this setting include endocrine therapy with targeted agents, such as CDK4/6 inhibitors and phosphoinositide 3-kinase (PI3K) inhibitors for hormone receptor-positive disease, anti-HER2 targeted therapy for HER2-positive disease, poly(ADP-ribose) polymerase inhibitors for BRCA1/2 mutation carriers and immunotherapy currently for part of triple-negative disease. Innovation technologies of precision medicine may guide individualized treatment escalation or de-escalation in the future. In this review, we summarized the latest scientific information and discussed the future perspectives on breast cancer.
| S-EPMC9558690 | biostudies-literature
Project description:INTRODUCTION:In recent years, computational polypharmacology has gained significant attention to study the promiscuous nature of drugs. Despite tremendous challenges, community-wide efforts have led to a variety of novel approaches for predicting drug polypharmacology. In particular, some rapid advances using machine learning and artificial intelligence have been reported with great success. AREAS COVERED:In this article, the authors provide a comprehensive update on the current state-of-the-art polypharmacology approaches and their applications, focusing on those reports published after our 2017 review article. The authors particularly discuss some novel, groundbreaking concepts, and methods that have been developed recently and applied to drug polypharmacology studies. EXPERT OPINION:Polypharmacology is evolving and novel concepts are being introduced to counter the current challenges in the field. However, major hurdles remain including incompleteness of high-quality experimental data, lack of in vitro and in vivo assays to characterize multi-targeting agents, shortage of robust computational methods, and challenges to identify the best target combinations and design effective multi-targeting agents. Fortunately, numerous national/international efforts including multi-omics and artificial intelligence initiatives as well as most recent collaborations on addressing the COVID-19 pandemic have shown significant promise to propel the field of polypharmacology forward.
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Project description:Colonic lipomas are rare and can sometimes cause intussusception. The aim of this review was to define the presentation and possible management for colocolic intussusception caused by colonic lipomas. A systematic search for patients with colocolic intussusception caused by colonic lipoma, including all available reports up to 2021. Epidemiological, clinical, laboratory, and instrumental data and details about the treatments performed were gathered. Colocolic intussusception caused by lipoma is more frequent in women (57%), occurring between 40 and 70 years of age. Up to 83% of patients report abdominal pain, followed by constipation (18%), rectal bleeding (16%), and diarrhea (12%), with abdominal tenderness (37%), and distension in 16%, whereas 24% have a negative exploration. CT (72%) and colonoscopy (62%) are more commonly able to diagnose the entity. The most common location of intussusception is the transverse colon (28%). The surgical operation varies according to the site. The average dimensions of the lipoma are 59.81 × 47.84 × 38.9 mm3. A correct preoperative diagnosis of colonic lipoma causing intussusception might not be easy. Despite nonspecific clinical and laboratory presentation, cross-sectional imaging can help differential diagnosis. Surgical treatment depends on the localization.
| S-EPMC8584916 | biostudies-literature
Project description:Hypertension is the major risk factor for cardiovascular morbidity and mortality. Matter of fact, untreated hypertension can worsen the overall health, whereas pharmacotherapy can play an important role in lowering the risk of high blood pressure in hypertensive patients. However, persistent uncontrolled hypertension remains an unsolved condition characterized by non-adherence to medication and increased sympathetic activity. This paper will review the non-pharmacological treatments for resistant hypertension (RH) that have emerged in recent years. In addition, the technologies developed in device-based RH therapy, as well as the clinical trials that support their use, will be discussed. Indeed, the novel device-based approaches that target RH present a promising therapy which has been supported by several studies and clinical trials, whereas drug non-adherence and high sympathetic activity are known to be the main causes of RH. Nevertheless, some additional aspects of these RH systems need to be tested in the near future, with a particular focus on the device's design and availability of randomized controlled trials.
| S-EPMC9523625 | biostudies-literature
Project description:BackgroundPost-mastectomy pain syndrome (PMPS) is a known debilitating surgical complication. While research on prevention, risk factors, and treatments have been conducted, there remains no cohesive treatment paradigm. The aim of our study is to synthesize the existing evidence on PMPS treatment, which may facilitate the implementation of standardized, effective management strategies.MethodsUsing Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive search was developed and translated for MEDLINE, Cochrane Library, EMBASE, CINAHL, PsycINFO, Web of Science, and ClinicalTrials.gov. The databases were searched using a combination of free terms, phrase searching, and database-specific controlled vocabulary related to PMPS. All unique records were by two independent reviewers. Publications on chronic (>3 months duration) pain after breast cancer-related surgery were included. Limited case series, case reports, and editorials were not included.ResultsA total of 3402 articles from the years 1946-2019 resulted from the literature search after deduplication. Twenty-seven articles met final inclusion criteria for analysis, which revealed 10 major treatment modalities: fat grafting, neuroma surgery, lymphedema surgery, nerve blocks and neurolysis, laser, antidepressants, neuromodulators, physical therapy, mindfulness-based cognitive therapy, and capsaicin.ConclusionsIn this review, we present a comprehensive assessment of the treatments available for PMPS that may help guide breast surgeons and reconstructive surgeons to employ the most effective treatment strategies for these patients. This review supports the importance of multimodal, multidisciplinary care in improving the management of PMPS.
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