The Use of CRISPR-Cas9 Genetic Technology in Cardiovascular Disease: A Comprehensive Review of Current Progress and Future Prospective.

Over the last century, there have been major landmark developments in the field of medicine, enabling us to control and cure various diseases on a larger scale. A few of these include the discovery of antibiotics, the development of vaccines, and the origin of organ and tissue transplants. The continued quest for innovation in microbiology and medicine has helped humankind save millions of lives and decrease morbidity at the global level. Genetic medicine has grown significantly in the last two decades and appears to be the next frontier of curative therapies for chronic diseases. One important landmark in genetic medicine is the development of CRISPR (clustered, regularly interspaced short palindromic repeats) technology. In this article, we describe the basic structure and function of the CRISPR-Cas9 system, which, simply put, consists of an RNA part and a protein. It works as a molecular scissor that can perform targeted cuts followed by repairs in and around the genes of interest to attain favorable translational outcomes. We focused on summarizing recent studies using CRISPR-Cas9 technology in diagnosing and treating cardiovascular disease. These studies are primarily experimental and limited to animal models. However, their results are promising enough to anticipate that this technology will undoubtedly be available in clinical medicine in the coming years. CRISPR-Cas9-mediated gene editing has been used to study and potentially treat congenital heart disease, hyperlipidemias, arrhythmogenic cardiomyopathies, and the prevention of ischemia-reperfusion injury. Despite the current progress, we recognize the several challenges this technology faces, including funding for research, improving precision and reproducible results for human subjects, and establishing protocols for ethical compliance so that it is acceptable to the scientific community and the general public.

Application of organoid technology in the human health risk assessment of microplastics: A review of progresses and challenges.

Microplastic (MP) pollution has become a global environmental issue, and increasing concern has been raised about its impact on human health. Current studies on the toxic effects and mechanisms of MPs have mostly been conducted in animal models or in vitro cell cultures, which have limitations regarding inter-species differences or stimulation of cellular functions. Organoid technology derived from human pluripotent or adult stem cells has broader prospects for predicting the potential health risks of MPs to humans. Herein, we reviewed the current application advancements and opportunities for different organoids, including brain, retinal, intestinal, liver, and lung organoids, to assess the human health risks of MPs. Organoid techniques accurately simulate the complex processes of MPs and reflect phenotypes related to diseases caused by MPs such as liver fibrosis, neurodegeneration, impaired intestinal barrier and cardiac hypertrophy. Future perspectives were also proposed for technological innovation in human risk assessment of MPs using organoids, including extending the lifespan of organoids to assess the chronic toxicity of MPs, and reconstructing multi-organ interactions to explore their potential in studying the microbiome-gut-brainaxis effect of MPs.

Simple, inexpensive, and rapid approach to detect changes in the structure of soil free-living nematodes.

A general limitation of ecological investigations based on nematodes is related to the difficult and time-consuming taxonomic identification of species. Therefore, nematologists are investing many efforts to develop alternative approaches as proxies applicable in biomonitoring assessment. Recently, an alternative method that combines morpho-functional traits was proposed for detecting assemblage changes of marine nematodes. In view of the promising results, it was tested the same approach to document taxonomic structure changes of soil free-living and plant parasitic nematodes. Specifically, this attempt was carried out using three data sets that include studies from various European regions and different types of ecosystems: forests, grasslands and maize crops. Multivariate statistical analysis revealed that the simple combination of the four traits (i.e., buccal cavity cuticularization occurrence, amphideal fovea size and shape, morphology of the cuticle and pharynx) in a single code number perfectly mirrors the taxonomic structure trends of the nematode assemblage at genus level. Therefore, we predict that similar results can be also obtained by directly encoding nematode specimens with the selected traits and we point to new important advances if this procedure can be coupled with advanced machine learning.

Disease Modifying Strategies in Multiple Sclerosis: New Rays of Hope to Combat Disability?

Multiple sclerosis (MS) is the most prevalent chronic autoimmune inflammatory- demyelinating disorder of the central nervous system (CNS). It usually begins in young adulthood, mainly between the second and fourth decades of life. Usually, the clinical course is characterized by the involvement of multiple CNS functional systems and by different, often overlapping phenotypes. In the last decades, remarkable results have been achieved in the treatment of MS, particularly in the relapsing- remitting (RRMS) form, thus improving the long-term outcome for many patients. As deeper knowledge of MS pathogenesis and respective molecular targets keeps growing, nowadays, several lines of disease-modifying treatments (DMT) are available, an impressive change compared to the relative poverty of options available in the past. Current MS management by DMTs is aimed at reducing relapse frequency, ameliorating symptoms, and preventing clinical disability and progression. Notwithstanding the relevant increase in pharmacological options for the management of RRMS, research is now increasingly pointing to identify new molecules with high efficacy, particularly in progressive forms. Hence, future efforts should be concentrated on achieving a more extensive, if not exhaustive, understanding of the pathogenetic mechanisms underlying this phase of the disease in order to characterize novel molecules for therapeutic intervention. The purpose of this review is to provide a compact overview of the numerous currently approved treatments and future innovative approaches, including neuroprotective treatments as anti-LINGO-1 monoclonal antibody and cell therapies, for effective and safe management of MS, potentially leading to a cure for this disease.

Prevalence of Diabetes in India: A Review of IDF Diabetes Atlas 10th Edition.

Diabetes is a severe chronic disease that arises when insulin generation is insufficient, or the generated insulin cannot be used in the body, resulting a long-term metabolic disorder. Diabetes affects an estimated 537 million adults worldwide between the age of 20 to 79 (10.5% of all adults in this age range). By 2030, 643 million people will have diabetes globally, increasing to 783 million by 2045. According to the IDF 10th edition, the incidence of diabetes has been rising in South-East Asia (SEA) nations for at least 20 years, and current estimates have outperformed all previous forecasts. This review aims to provide updated estimates and future projections of diabetes prevalence at the national and global levels by using data from the 10th edition of the IDF Diabetes Atlas 2021. For this review, we studied more than 60 previously published related articles from various sources, such as PubMed and Google Scholar, and we extracted 35 studies out of 60. however, we used only 34 studies directly related to diabetes and its prevalence at the global, SEA, and Indian levels. This review article concludes that in 2021 more than 1 in 10 adults worldwide developed diabetes. The estimated prevalence of diabetes in adults (20 to 79 years) has more than tripled since the first edition in 2000, rising from an estimated 151 million (4.6% of the world's population at the time) to 537.5 million (10.5%) of the world's population today. The prevalence rate will be higher than 12.8% by 2045. In addition, this study indicates that the incidence of diabetes in the world, Southeast Asia, and India was 10.5%, 8.8%, and 9.6%, respectively, throughout 2021 and will rise to 12.5%, 11.5%, and 10.9%, respectively by 2045.

Hereditary neuropathy.

The hereditary neuropathies, collectively referred as Charcot-Marie-Tooth disease (CMT) and related disorders, are heterogeneous genetic peripheral nerve disorders that collectively comprise the commonest inherited neurological disease with an estimated prevalence of 1:2500 individuals. The field of hereditary neuropathies has made significant progress in recent years with respect to both gene discovery and treatment as a result of next-generation sequencing (NGS) approach. These investigations which have identified over 100 causative genes and new mutations have made the classification of CMT even more challenging. Despite so many different mutated genes, the majority of CMT forms share a similar clinical phenotype, and due to this phenotypic homogeneity, genetic testing in CMT is increasingly being performed through the use of NGS panels. The majority of patients still have a mutation in one the four most common genes (PMP22 duplication-CMT1A, MPZ-CMT1B, GJB1-CMTX1, and MFN2-CMT2A). This chapter focuses primarily on these four forms and their potential therapeutic approaches.

Perceived Future Outcomes of Unsuccessful Treatment and Their Association with Treatment Persistence Among Type-2 Diabetes Patients: A Cross-Sectional Content Analysis.

INTRODUCTION: Despite the known strong association between patients' knowledge of outcomes of type 2 diabetes mellitus (T2DM) and treatment persistence, this knowledge in this patient population requires further clarification. The aim of our study was to reveal the perception of unsuccessful treatment outcomes among patients with T2DM and its association with treatment persistence by analysing answers to open-ended questions. METHODS: In this cross-sectional study, 106 patients with T2DM who lived in Fukushima Prefecture, Japan, had a medical record in the Fukushima National Health Insurance Organisation database and had no cognitive problems were enrolled by purposive sampling. Treatment status was defined as "non-persistent" when a participant's treatment medical record was absent for a continuous period of ≥ 6 months; otherwise, it was referred to as "persistent". We asked about the possible future problems of untreated T2DM, inductively classified the open answers into 15 codes and then statistically examined the association between these codes and treatment persistence using logistic regression analysis adjusted for age and sex. RESULTS: Persistent treatment was prevalent among participants who mentioned the code "treatment", which encompasses the terms that indicated invasiveness, such as dialysis, insulin injection, and shots (odds ratio 4.339; 95% confidence interval 1.104-17.055). CONCLUSION: Persistent treatment was prevalent among patients with T2DM who mentioned the code "treatment", suggesting that these patients may anticipate a threat due to the invasiveness of diabetes and thus participate in persistent treatment to avoid this threat. Healthcare professionals should provide appropriate information and supportive conditions to achieve both a reduced feeling of threat and persistent treatment engagement.

A review of the current state of single-cell proteomics and future perspective.

Single-cell methodologies and technologies have started a revolution in biology which until recently has primarily been limited to deep sequencing and imaging modalities. With the advent and subsequent torrid development of single-cell proteomics over the last 5 years, despite the fact that proteins cannot be amplified like transcripts, it has now become abundantly clear that it is a worthy complement to single-cell transcriptomics. In this review, we engage in an assessment of the current state of the art of single-cell proteomics including workflow, sample preparation techniques, instrumentation, and biological applications. We investigate the challenges associated with working with very small sample volumes and the acute need for robust statistical methods for data interpretation. We delve into what we believe is a promising future for biological research at single-cell resolution and highlight some of the exciting discoveries that already have been made using single-cell proteomics, including the identification of rare cell types, characterization of cellular heterogeneity, and investigation of signaling pathways and disease mechanisms. Finally, we acknowledge that there are a number of outstanding and pressing problems that the scientific community vested in advancing this technology needs to resolve. Of prime importance is the need to set standards so that this technology becomes widely accessible allowing novel discoveries to be easily verifiable. We conclude with a plea to solve these problems rapidly so that single-cell proteomics can be part of a robust, high-throughput, and scalable single-cell multi-omics platform that can be ubiquitously applied to elucidating deep biological insights into the diagnosis and treatment of all diseases that afflict us.

Monkeypox Virus and Other Emerging Outbreaks: An Overview and Future Perspective.

Monkeypox (MPX) is a zoonotic disease caused by the MPX virus from the poxviridae family of orthopoxviruses. Typically, endemic in central and west Africa, it has now become a matter of concern since cases have been reported in non-endemic countries around mid-June 2022, especially in the European region, with the transmission not related to travel. The diagnosis is made by PCR testing of the skin lesions. Even though treatment is symptomatic, antiretrovirals, such as tecovirimat, are used in severe cases. Vaccination with second and third generation vaccines is approved for prophylaxis in high risk individuals. Unfortunately, these options of treatment and prevention are only available in high income countries at the moment. This review, through a thorough literature search of articles from 2017 onward, focuses on epidemiology, clinical manifestations, challenges, treatment, prevention and control of MPX virus and how they can be corelated with other viral outbreaks including COVID-19, Acute Hepatitis of unknown origin, Measles and Dengue, to better predict and therefore prevent its transmission. The previous COVID-19 pandemic increased the disease burden on healthcare infrastructure of low-middle income countries, therefore, this recent MPX outbreak calls for a joint effort from healthcare authorities, political figures, and NGOs to combat the disease and prevent its further spread not only in high income but also in middle- and low-income countries.

Summary of volume 51: DNA damage and double-strand breaks.

DNA damage and breaks are events that happen to DNA which exert a variety of influence on cell physiology including inhibition of DNA synthesis, repair response, cell cycle effect and cell death. Thus, it is important to deepened understanding of these events. In volume 51, we discussed topics including (1) assays to detect double-strand breaks, (2) conditions leading to double-strand breaks, (3) effects of irradiation, (4) DNA structure and chromatins, and (5) direct and indirect effect on DNA. Contributing authors and a table of contents for volume 51 are mentioned. We also discuss further issues and topics that need to be featured in future volumes. These include DNA damage sensors, DNA damage response proteins, and double-strand break repair pathways.

One small step in time, one giant leap for DMPK kind - a CRO perspective of the evolving core discipline of drug development.

As the Space Race or Formula 1 drives innovation, efficiency and progress in home technology and home car markets, Drug Metabolism and Pharmacokinetics (DMPK) drives scientific innovation and value for drug development companies. Stand still and fall behind as the saying goes, and these analogies are true as much in the design and conduct of DMPK studies as they are in the technology and manufacturing sectors.This short review showcases the impact that DMPK has had on drug development and how it has changed in the last 10 years, illustrating the value added scientific benefit, cost and time saving, that innovative DMPK program design and study conduct have. Examples and case studies spanning novel in vitro alternatives such as organ-on-a-chip (OOAC) developments; use of in vivo microsampling across small and large animal species; challenging historical paradigms in Absorption, Distribution, Metabolism and Excretion (ADME) studies; and embracing new technologies to address regulatory concerns, are presented.The continual pace of change has kept DMPK at the core of pharmaceutical, crop and chemical evaluation, and this is set to continue as regulators use this discipline to inform decision-making. With new modalities and new scientific questions, DMPK will continue to evolve, with the likes of new in vitro, in vivo and in silico models becoming central to candidate selection and progression.

How Does Income Heterogeneity Affect Future Perspectives on Food Consumption? Empirical Evidence from Urban China.

China is undergoing a rapid dietary transition as well as a changing income distribution. In this paper, we examine the impacts of income heterogeneity on the prediction of food consumption using a dataset that covered 22,210 urban households in China's 6 provinces. The two-stage Exact Affine Stone Index Implicit Marshallian Demand System (EASI demand system) model, which deals with the problem of censoring and endogeneity, is applied to estimate demand elasticity across income strata. Additionally, a dynamic simulation method considering income heterogeneity is conducted to predict future food consumption trends. The results reveal that income elasticity follows a decreasing trend with income growth. Furthermore, the results show that the consumption of major food items in the 15th period will increase by 7.9% to 42.0% over the base period. The growth potential of low-income groups is significantly higher than that of middle- and high-income groups. However, the prediction results may be overestimated if the differences in consumer behavior across income groups and the dynamic simulation procedure are not taken into account. Our study indicates that the consumption features of different income groups need to be included in food consumption forecasts. Moreover, the government should formulate food policies for different income groups to promote a sustainable food system transformation.

Management of Nursing Resource during the Covid 19 Pandemic: Lessons on the Ground.

During the covid 19 pandemic, management of nursing resource which forms the crux of patient care emerged as one of the major challenges amongst many. The strategies for staff mobilization, redeployment and recruitment, along with laying down standard operating procedures evolved as the pandemic progressed. The safety of the staff has to be a major focus area. Guidelines for covid duty exemption, orientation and training of staff must be drafted, reviewed and revised as required. Issues related to accommodation, psychosocial support and wellbeing have to be addressed. It is very important to adapt to the ever changing needs for nursing resource and be vigilant for emerging issues for an effective response to the pandemic.

Therapeutic Potential of Glucagon-like Peptide-1 Agonists in Polycystic Ovary Syndrome: From Current Clinical Evidence to Future Perspectives.

Despite the continuous effort to understand the pathophysiology and determine potential therapeutic targets, PCOS treatment largely depends on lifestyle intervention and symptomatic management of individual signs and symptoms. International guidelines recognize the importance of weight reduction as a cornerstone for the achievement of better metabolic, reproductive, and cardiovascular outcomes in PCOS women who are overweight or obese. With its profound weight loss potential in patients with or without diabetes, the administration of GLP-1 receptor agonists has been investigated in overweight/obese women with PCOS in several single-center randomized control trials with considerable variation in the dosing regimen, follow-up duration, and outcome measurements over recent years. Most trials reported superior weight loss effects of GLP-1 receptor agonists compared to lifestyle changes or metformin, with additional metabolic, reproductive, and cardiovascular benefits in this population. However, their use is currently not widely accepted by the clinical community that treats this population. The major concern is how to balance the reproductive and metabolic treatment strategies since the use of GLP-1 receptor agonists requires effective contraception while on therapy and a washout period before pregnancy. Both approaches are not mutually exclusive, yet the best choice requires a careful assessment of the clinical context. Knowing a patient's individual circumstances, precise clinical sub-phenotyping, and regular monitoring are crucial components for the safe and effective use of these new tools. In the present narrative review, we explore the current clinical evidence and provide the future perspectives and challenges for their implementation in PCOS management.

Osteoporosis in 10 years time: a glimpse into the future of osteoporosis.

Patients living with osteoporosis are projected to increase dramatically in the next decade. Alongside the forecasted increased societal and economic burden, we will live a crisis of fractures. However, we will have novel pharmacological treatment to face this crisis and, more importantly, new optimized treatment strategies. Fracture liaison services will be probably implemented on a large scale worldwide, helping to prevent additional fractures in high-risk patients. In the next decade, novel advances in the diagnostic tools will be largely available. Moreover, new and more precise fracture risk assessment tools will change our ability to detect patients at high risk of fractures. Finally, big data and artificial intelligence will help us to move forward into the world of precision medicine. In the present review, we will discuss the future epidemiology and costs of osteoporosis, the advances in early and accurate diagnosis of osteoporosis, with a special focus on biomarkers and imaging tools. Then we will examine new and refined fracture risk assessment tools, the role of fracture liaison services, and a future perspective on osteoporosis treatment.

Limitations and future directions of application of the Fenton-like process in micropollutants degradation in water and wastewater treatment: A critical review.

Growing water scarcity and pollution are the main challenges that scientists need to focus on currently. Fenton-like processes are promising for applications related to water and wastewater treatment. Although there have been reviews on the fundamentals and applications of Fenton oxidation, a review focusing on the limitations of Fenton oxidation and their possible solutions is still insufficient. This review summarises the features, advantages, and drawbacks of the classic Fenton process. A comprehensive literature survey was conducted to review studies conducted over the last few decades dealing with the application of Fenton processes to organic pollutant removal from water and wastewater. The present overview highlights the modifications of Fenton processes focusing on industrial applications in water and wastewater treatment, especially for micropollutant degradation. Additionally, this study reviews the possibilities and future directions of research on Fenton-like processes to enable the incorporation of Fenton-based methods into existing water and wastewater treatment technologies, including industrial wastewater. It also presents a novel technological solution and improvements to the Fenton-like process to improve the efficiency and reduce the cost.

Current status and future perspective of radiopharmaceuticals in China.

Radiopharmaceuticals are essential components of nuclear medicine and serve as one of the cornerstones of molecular imaging and precision medicine. They provide new means and approaches for early diagnosis and treatment of diseases. After decades of development and hard efforts, a relatively matured radiopharmaceutical production and management system has been established in China with high-quality facilities. This review provides an overview of the current status of radiopharmaceuticals on production and distribution, clinical application, and regulatory supervision and also describes some important advances in research and development and clinical translation of radiopharmaceuticals in the past 10 years. Moreover, some prospects of research and development of radiopharmaceuticals in the near future are discussed.

Four-Dimensional Printing for Hydrogel: Theoretical Concept, 4D Materials, Shape-Morphing Way, and Future Perspectives.

The limitations and challenges possessed in static 3D materials necessitated a new era of 4D shape-morphing constructs for wide applications in diverse fields of science. Shape-morphing behavior of 3D constructs over time is 4D design. Four-dimensional printing technology overcomes the static nature of 3D, improves substantial mechanical strength, and instills versatility and clinical and nonclinical functionality under set environmental conditions (physiological and artificial). Four-dimensional printing of hydrogel-forming materials possesses remarkable properties compared to other printing techniques and has emerged as the most established technique for drug delivery, disease diagnosis, tissue engineering, and biomedical application using shape-morphing materials (natural, synthetic, semisynthetic, and functionalized) in response to single or multiple stimuli. In this article, we addressed a fundamental concept of 4D-printing evolution, 4D printing of hydrogel, shape-morphing way, classification, and future challenges. Moreover, the study compiled a comparative analysis of 4D techniques, 4D products, and mechanical perspectives for their functionality and shape-morphing dynamics. Eventually, despite several advantages of 4D technology over 3D technique in hydrogel fabrication, there are still various challenges to address with using current advanced and sophisticated technology for rapid, safe, biocompatible, and clinical transformation from small-scale laboratory (lab-to-bed translation) to commercial scale.

Anticancer Effects and Mechanisms of OSW-1 Isolated From Ornithogalum saundersiae: A Review.

For centuries, cancer has been a lingering dark cloud floating on people's heads. With rapid population growth and aging worldwide, cancer incidence and mortality are growing rapidly. Despite major advances in oncotherapy including surgery, radiation and chemical therapy, as well as immunotherapy and targeted therapy, cancer is expected be the leading cause of premature death in this century. Nowadays, natural compounds with potential anticancer effects have become an indispensable natural treasure for discovering clinically useful agents and made remarkable achievements in cancer chemotherapy. In this regards, OSW-1, which was isolated from the bulbs of Ornithogalum saundersiae in 1992, has exhibited powerful anticancer activities in various cancers. However, after almost three decades, OSW-1 is still far from becoming a real anticancer agent for its anticancer mechanisms remain unclear. Therefore, in this review we summarize the available evidence on the anticancer effects and mechanisms of OSW-1 in vitro and in vivo, and some insights for researchers who are interested in OSW-1 as a potential anticancer drug. We conclude that OSW-1 is a potential candidate for anticancer drugs and deserves further study.