Genetic Alchemy unveiled: MicroRNA-mediated gene therapy as the Artisan craft in the battlefront against hepatocellular carcinoma-a comprehensive chronicle of strategies and innovations.

Investigating therapeutic miRNAs is a rewarding endeavour for pharmaceutical companies. Since its discovery in 1993, our understanding of miRNA biology has advanced significantly. Numerous studies have emphasised the disruption of miRNA expression in various diseases, making them appealing candidates for innovative therapeutic approaches. Hepatocellular carcinoma (HCC) is a significant malignancy that poses a severe threat to human health, accounting for approximately 70%-85% of all malignant tumours. Currently, the efficacy of several HCC therapies is limited. Alterations in various biomacromolecules during HCC progression and their underlying mechanisms provide a basis for the investigation of novel and effective therapeutic approaches. MicroRNAs, also known as miRNAs, have been identified in the last 20 years and significantly impact gene expression and protein translation. This atypical expression pattern is strongly associated with the onset and progression of various malignancies. Gene therapy, a novel form of biological therapy, is a prominent research area. Therefore, miRNAs have been used in the investigation of tumour gene therapy. This review examines the mechanisms of action of miRNAs, explores the correlation between miRNAs and HCC, and investigates the use of miRNAs in HCC gene therapy.

Heartfelt living: Deciphering the link between lifestyle choices and cardiovascular vitality.

Cardiovascular diseases (CVDs) are still leading to a significant number of deaths worldwide despite the remarkable advancements in medical technology and pharmacology. Managing patients with established CVDs is a challenge for healthcare providers as it requires reducing the chances of recurring cardiovascular events. On the other hand, changing one's way of life can also significantly impact this area, reducing the likelihood of cardiovascular disease and death through their unique advantages. Consequently, it is advisable for healthcare providers to regularly advise their patients with coronary issues to participate in organized physical exercise and improve their overall physical activity. Additionally, patients should adhere to a diet that promotes heart health, cease smoking, avoid exposure to secondhand smoke, and address any psychosocial stressors that may heighten the risk of cardiovascular problems. These lifestyle therapies, whether used alongside drug therapy or on their own in patients who may have difficulty tolerating medications, face financial barriers, or experience ineffectiveness, can substantially reduce cardiovascular mortality and the likelihood of recurring cardiac events. Despite the considerable advancements in creating interventions, it is still necessary to determine the optimal intensity, duration, and delivery method for these interventions. Furthermore, it is crucial to carry out further investigations incorporating extended monitoring and assessment of clinical outcomes to get a more comprehensive comprehension of the efficacy of these therapies. Presenting the findings within the framework of "lifestyle medicine," this review seeks to offer a thorough synopsis of the most recent scientific investigations into the potential of behavioral modifications to lower cardiovascular disease risk.

Beyond the silence: A comprehensive exploration of long non-coding RNAs as genetic whispers and their essential regulatory functions in cardiovascular disorders.

Long non-coding RNAs (lncRNAs) are RNA molecules that regulate gene expression at several levels, including transcriptional, post-transcriptional, and translational. They have a length of more than 200 nucleotides and cannot code. Many human diseases have been linked to aberrant lncRNA expression, highlighting the need for a better knowledge of disease etiology to drive improvements in diagnostic, prognostic, and therapeutic methods. Cardiovascular diseases (CVDs) are one of the leading causes of death worldwide. LncRNAs play an essential role in the complex process of heart formation, and their abnormalities have been associated with several CVDs. This Review article looks at the roles and relationships of long non-coding RNAs (lncRNAs) in a wide range of CVDs, such as heart failure, myocardial infarction, atherosclerosis, and cardiac hypertrophy. In addition, the review delves into the possible uses of lncRNAs in diagnostics, prognosis, and clinical treatments of cardiovascular diseases. Additionally, it considers the field's future prospects while examining how lncRNAs might be altered and its clinical applications.

Hemophilia Healing with AAV: Navigating the Frontier of Gene Therapy.

Gene therapy for hemophilia has advanced tremendously after thirty years of continual study and development. Advancements in medical science have facilitated attaining normal levels of Factor VIII (FVIII) or Factor IX (FIX) in individuals with haemophilia, thereby offering the potential for their complete recovery. Despite the notable advancements in various countries, there is significant scope for further enhancement in haemophilia gene therapy. Adeno-associated virus (AAV) currently serves as the primary vehicle for gene therapy in clinical trials targeting haemophilia. Subsequent investigations will prioritize enhancing viral capsid structures, transgene compositions, and promoters to achieve heightened transduction efficacy, diminished immunogenicity, and more predictable therapeutic results. The present study indicates that whereas animal models have transduction efficiency that is over 100% high, human hepatocytes are unable to express clotting factors and transduction efficiency to comparable levels. According to the current study, achieving high transduction efficiency and high levels of clotting factor expression in human hepatocytes is still insufficient. It is also crucial to reduce the risk of cellular stress caused by protein overload. Despite encountering various hurdles, the field of haemophilia gene therapy holds promise for the future. As technology continues to advance and mature, it is anticipated that a personalized therapeutic approach will be developed to cure haemophilia effectively.

Cardiovascular diseases crossroads: cGAS-STING signaling and disease progression.

It is now widely accepted that inflammation is critical in cardiovascular diseases (CVD). Here, studies are being conducted on how cyclic GMP-AMP synthase (cGAS), a component of innate immunity's DNA-sensing machinery, communicates with the STING receptor, which is involved in activating the immune system's antiviral response. Significantly, a growing body of research in recent years highlights the strong activation of the cGAS-STING signalling pathways in several cardiovascular diseases, such as myocardial infarction, heart failure, and myocarditis. This developing collection of research emphasises these pathways' crucial role in initiating and advancing cardiovascular disease. In this extensive narrative, we explore the role of the cGAS-STING pathway in the development of CVD. We elaborate on the basic mechanisms involved in the onset and progression of CVD. This review explores the most recent developments in the recognition and characterization of cGAS-STING pathway. Additionally, it considers the field's future prospects while examining how cGAS-STING pathway might be altered and its clinical applications for cardiovascular diseases.

Beyond the beat: A pioneering investigation into exercise modalities for alleviating diabetic cardiomyopathy and enhancing cardiac health.

Patients with preexisting cardiovascular disease or those at high risk for developing the condition are often offered exercise as a form of therapy. Patients with cancer who are at an increased risk for cardiovascular issues are increasingly encouraged to participate in exercise-based, interdisciplinary programs due to the positive correlation between these interventions and clinical outcomes following myocardial infarction. Diabetic cardiomyopathy (DC) is a cardiac disorder that arises due to disruptions in the homeostasis of individuals with diabetes. One of the primary reasons for mortality in individuals with diabetes is the presence of cardiac structural damage and functional abnormalities, which are the primary pathological features of DC. The aetiology of dilated cardiomyopathy is multifaceted and encompasses a range of processes, including metabolic abnormalities, impaired mitochondrial function, dysregulation of calcium ion homeostasis, excessive cardiomyocyte death, and fibrosis. In recent years, many empirical investigations have demonstrated that exercise training substantially impacts the prevention and management of diabetes. Exercise has been found to positively impact the recovery of diabetes and improve several metabolic problem characteristics associated with DC. One potential benefit of exercise is its ability to increase systolic activity, which can enhance cardiometabolic and facilitate the repair of structural damage to the heart caused by DC, leading to a direct improvement in cardiac health. In contrast, exercise has the potential to indirectly mitigate the pathological progression of DC through its ability to decrease circulating levels of sugar and fat while concurrently enhancing insulin sensitivity. A more comprehensive understanding of the molecular mechanism via exercise facilitates the restoration of DC disease must be understood. Our goal in this review was to provide helpful information and clues for developing new therapeutic techniques for motion alleviation DC by examining the molecular mechanisms involved.

Cardiovascular challenges in the era of antiretroviral therapy for AIDS/ HIV: A comprehensive review of research advancements, pathophysiological insights, and future directions.

Cardiovascular disease, particularly coronary heart disease, is becoming more common among those living with HIV. Individuals with HIV face an increased susceptibility to myocardial infarction, also known as a heart attack, as compared to the general population in developed countries. This heightened risk can be attributed mainly to the presence of effective antiretroviral drugs and the resulting longer lifespan. Some cardiac issues linked to non-antiretroviral medications, including myocarditis, endocarditis, cardiomyopathy with dilation, pulmonary hypertension, and oedema of the heart, may affect those not undergoing highly active antiretroviral therapy (ART). Impaired immune function and systemic inflammation are significant contributors to this phenomenon after initiating highly aggressive antiretroviral treatment ART. It is becoming more challenging to determine the best course of treatment for HIV-associated cardiomyopathy due to new research suggesting that protease inhibitors might have a negative impact on the development of HF. Currently, the primary focus of research on ART medications is centered on the cardiovascular adverse effects of nucleoside reverse transcriptase inhibitors and protease inhibitors. This review paper thoroughly evaluates the advancements achieved in cardiovascular disease research and explores the potential implications for prospects. Additionally, it considers the field's future prospects while examining how ART might be altered and its clinical applications.

Natural Allies for Heart Health: Nrf2 Activation and Cardiovascular Disease Management.

The term "cardiovascular diseases" (CVD) refers to various ailments that affect the heart and blood vessels, including myocardial ischemia, congenital heart defects, heart failure, rheumatic heart disease, hypertension, peripheral artery disease, atherosclerosis, and cardiomyopathies. Despite significant breakthroughs in preventative measures and treatment choices, CVDs significantly contribute to morbidity and mortality, imposing a considerable financial burden. Oxidative stress (OS) is a fundamental contributor to the development and progression of CVDs, resulting from an inherent disparity in generating reactive oxygen species. The disparity above significantly contributes to the aberrant operation of the cardiovascular system. To tackle this issue, therapeutic intervention primarily emphasizes the nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor crucial in regulating endogenous antioxidant defense systems against OS. The Nrf2 exhibits potential as a promising target for effectively managing CVDs. Significantly, an emerging field of study is around the utilization of natural substances to stimulate the activation of Nrf2, hence facilitating the promotion of cardioprotection. This technique introduces a new pathway for treating CVD. The substances above elicit their advantageous effects by mitigating the impact of OS via initiating Nrf2 signaling. The primary objective of our study is to provide significant insights that can contribute to advancing treatment methods, including natural products. These strategies aim to tackle the obstacles associated with CVDs.

The Multifunctional TRPC6 Protein: Significance in the Field of Cardiovascular Studies.

Cardiovascular disease is the leading cause of death, medical complications, and healthcare costs. Although recent advances have been in treating cardiovascular disorders linked with a reduced ejection fraction, acutely decompensate cardiac failure remains a significant medical problem. The transient receptor potential cation channel (TRPC6) family responds to neurohormonal and mechanical stress, playing critical roles in cardiovascular diseases. Therefore, TRP C6 channels have great promise as therapeutic targets. Numerous studies have investigated the roles of TRP C6 channels in pain neurons, highlighting their significance in cardiovascular research. The TRPC6 protein exhibits a broad distribution in various organs and tissues, including the brain, nerves, heart, blood vessels, lungs, kidneys, gastrointestinal tract, and other bodily structures. Its activation can be triggered by alterations in osmotic pressure, mechanical stimulation, and diacylglycerol. Consequently, TRPC6 plays a significant role in the pathophysiological mechanisms underlying diverse diseases within living organisms. A recent study has indicated a strong correlation between the disorder known as TRPC6 and the development of cardiovascular diseases. Consequently, investigations into the association between TRPC6 and cardiovascular diseases have gained significant attention in the scientific community. This review explores the most recent developments in the recognition and characterization of TRPC6. Additionally, it considers the field's prospects while examining how TRPC6 might be altered and its clinical applications.

TME-targeted approaches of brain metastases and its clinical therapeutic evidence.

The tumor microenvironment (TME), which includes both cellular and non-cellular elements, is now recognized as one of the major regulators of the development of primary tumors, the metastasis of which occurs to specific organs, and the response to therapy. Development of immunotherapy and targeted therapies have increased knowledge of cancer-related inflammation Since the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCB) limit immune cells from entering from the periphery, it has long been considered an immunological refuge. Thus, tumor cells that make their way "to the brain were believed to be protected from the body's normal mechanisms of monitoring and eliminating them. In this process, the microenvironment and tumor cells at different stages interact and depend on each other to form the basis of the evolution of tumor brain metastases. This paper focuses on the pathogenesis, microenvironmental changes, and new treatment methods of different types of brain metastases. Through the systematic review and summary from macro to micro, the occurrence and development rules and key driving factors of the disease are revealed, and the clinical precision medicine of brain metastases is comprehensively promoted. Recent research has shed light on the potential of TME-targeted and potential treatments for treating Brain metastases, and we'll use that knowledge to discuss the advantages and disadvantages of these approaches.

Reprogramming tumor-associated macrophages as a unique approach to target tumor immunotherapy.

In the last ten years, it has become increasingly clear that tumor-infiltrating myeloid cells drive not just carcinogenesis via cancer-related inflammatory processes, but also tumor development, invasion, and metastasis. Tumor-associated macrophages (TAMs) in particular are the most common kind of leucocyte in many malignancies and play a crucial role in establishing a favorable microenvironment for tumor cells. Tumor-associated macrophage (TAM) is vital as the primary immune cell subset in the tumor microenvironment (TME).In order to proliferate and spread to new locations, tumors need to be able to hide from the immune system by creating an immune-suppressive environment. Because of the existence of pro-tumoral TAMs, conventional therapies like chemotherapy and radiotherapy often fail to restrain cancer growth. These cells are also to blame for the failure of innovative immunotherapies premised on immune-checkpoint suppression. Understanding the series of metabolic changes and functional plasticity experienced by TAMs in the complex TME will help to use TAMs as a target for tumor immunotherapy and develop more effective tumor treatment strategies. This review summarizes the latest research on the TAMs functional status, metabolic changes and focuses on the targeted therapy in solid tumors.

Role of LGMN in tumor development and its progression and connection with the tumor microenvironment.

Legumain (LGMN) has been demonstrated to be overexpressed not just in breast, prostatic, and liver tumor cells, but also in the macrophages that compose the tumor microenvironment. This supports the idea that LGMN is a pivotal protein in regulating tumor development, invasion, and dissemination. Targeting LGMN with siRNA or chemotherapeutic medicines and peptides can suppress cancer cell proliferation in culture and reduce tumor growth in vivo. Furthermore, legumain can be used as a marker for cancer detection and targeting due to its expression being significantly lower in normal cells compared to tumors or tumor-associated macrophages (TAMs). Tumor formation is influenced by aberrant expression of proteins and alterations in cellular architecture, but the tumor microenvironment is a crucial deciding factor. Legumain (LGMN) is an in vivo-active cysteine protease that catalyzes the degradation of numerous proteins. Its precise biological mechanism encompasses a number of routes, including effects on tumor-associated macrophage and neovascular endothelium in the tumor microenvironment. The purpose of this work is to establish a rationale for thoroughly investigating the function of LGMN in the tumor microenvironment and discovering novel tumor early diagnosis markers and therapeutic targets by reviewing the function of LGMN in tumor genesis and progression and its relationship with tumor milieu.

Current Landscape and Emerging Opportunities of Gene Therapy with Non-viral Episomal Vectors.

Gene therapy has proven to be extremely beneficial in the management of a wide range of genetic disorders for which there are currently no or few effective treatments. Gene transfer vectors are very significant in the field of gene therapy. It is possible to attach a non-viral attachment vector to the donor cell chromosome instead of integrating it, eliminating the negative consequences of both viral and integrated vectors. It is a safe and optimal express vector for gene therapy because it does not cause any adverse effects. However, the modest cloning rate, low expression, and low clone number make it unsuitable for use in gene therapy. Since the first generation of non-viral attachment episomal vectors was constructed, various steps have been taken to regulate their expression and stability, such as truncating the MAR element, lowering the amount of CpG motifs, choosing appropriate promoters and utilizing regulatory elements. This increases the transfection effectiveness of the non-viral attachment vector while also causing it to express at a high level and maintain a high level of stability. A vector is a genetic construct commonly employed in gene therapy to treat various systemic disorders. This article examines the progress made in the development of various optimization tactics for nonviral attachment vectors and the future applications of these vectors in gene therapy.

Role of circular RNAs in disease progression and diagnosis of cancers: An overview of recent advanced insights.

Tumor microenvironment (TME) is a crucial regulator of tumor progression and cells in the TME release a number of molecules that are responsible for anaplasticity, invasion, metastasis of tumor, establishing stem cell niches, up-regulation and down-regulation of various pathways in cancer cells, interfering with immune surveillance and immune escape. Moreover, they can serve as diagnostic markers, and determine effective therapies. Among them, CircRNAs have gained special attention due to their involvement in mutated pathways in cancers. By functioning as a molecular sponge for miRNAs, binding with proteins, and directing selective splicing. CircRNAs modify the immunological environment of cancers to promote their growth. Besides of critical role in tumor growth, circRNAs are emerging as potential candidates as biomarkers for diagnosis cancer therapy. Also, circRNAs vaccination even offers a novel approach to tumor immunotherapy. Over the recent years, studies are advocating that circRNAs have tissue specific tumor specific expression patterns, which indicates their potential clinical utility. Especially, circRNAs have emerged as potential predictive and prognostic biomarkers. Although, there has been significant progress in deciphering the role of circRNA in cancers, literature lacks comprehensive overview on this topic. Keeping in view of these significant discoveries, this review systematically discusses circRNA and their role in the tumor in different dimensions.

Mechanisms of gene regulation by histone degradation in adaptation of yeast: an overview of recent advances.

Histones are important component of eukaryotic cells chromatin and consist of arginine and lysine residues. Histones play an important role in the protection of DNA. Their contents significantly affect high-level chromatin structure formation, gene expression, DNA replication, and other important life activities. Protein degradation is an important regulatory mechanism of histone content. Recent studies have revealed that modification of amino acid sequence is directly related to histone breakdown. In addition, histone degradation is closely related to covalent modifications, such as ubiquitination and acetylation, which are considered to be driving factors in gene regulation. Gene regulation is an important mechanism in adaptation to the environment and survival of species. With the introduction of highly efficient technology, various mutations in histones have been identified in yeast. In the field of epigenetics and the transmission of chromatin states, two widely used model organisms are the budding yeast Saccharomyces cerevisiae and Schizosaccharomyces pombe. Higher eukaryotes can use their silent loci to maintain their epigenetic states and providing the base to investigate mechanisms underlying development. Therfore, both species have contributed a plethora of information on these mechanisms in both yeast and higher eukaryotes. This study focuses on the role of histone modifications in controlling telomeric silencing in Saccharomyces cerevisiae and centromeric silencing in S. pombe as examples of genetic loci that demonstrate epigenetic inheritance. In view of recent advances, this review focuses on the post-translational modification of histone amino acid residues and reviews the relationship between histone degradation and amino acid residue modification.

Applications of Extracellular Vesicles in Nervous System Disorders: An Overview of Recent Advances.

Diseases affecting the brain and spinal cord fall under the umbrella term "central nervous system disease". Most medications used to treat or prevent chronic diseases of the central nervous system cannot cross the blood-brain barrier (BBB) and hence cannot reach their intended target. Exosomes facilitate cellular material movement and signal transmission. Exosomes can pass the blood-brain barrier because of their tiny size, high delivery efficiency, minimal immunogenicity, and good biocompatibility. They enter brain endothelial cells via normal endocytosis and reverse endocytosis. Exosome bioengineering may be a method to produce consistent and repeatable isolation for clinical usage. Because of their tiny size, stable composition, non-immunogenicity, non-toxicity, and capacity to carry a wide range of substances, exosomes are indispensable transporters for targeted drug administration. Bioengineering has the potential to improve these aspects of exosomes significantly. Future research into exosome vectors must focus on redesigning the membrane to produce vesicles with targeting abilities to increase exosome targeting. To better understand exosomes and their potential as therapeutic vectors for central nervous system diseases, this article explores their basic biological properties, engineering modifications, and promising applications.

CdTe Quantum Dot-Functionalized P25 Titania Composite with Enhanced Photocatalytic NO2 Storage Selectivity under UV and Vis Irradiation.

Composite systems of P25 (titania) functionalized with thioglycolic acid (TGA)-capped CdTe colloidal quantum dots (QDs) were synthesized, structurally characterized, and photocatalytically tested in the photocatalytic NO x oxidation and storage during NO(g) + O2(g) reaction. Pure P25 yielded moderate-to-high NO conversion (31% in UV-A and 40% in visible (vis)) but exhibited extremely poor selectivity toward NO x storage in solid state (25% in UV-A and 35% in vis). Therefore, P25 could efficiently photooxidize NO(g) + O2(g) into NO2; however, it failed to store photogenerated NO2 and released toxic NO2(g) to the atmosphere. CdTe QD-functionalized P25 revealed a major boost in photocatalytic performance with respect to pure P25, where NO conversion reached 42% under UV-A and 43% under vis illumination, while the respective selectivity climbed up to 92 and 97%, rendering the CdTe/P25 composite system an efficient broad-band photocatalyst, which can harvest both UV-A and vis light efficiently and display a strong NO x abatement effect. Control experiments suggested that photocatalytic active sites responsible for the NO(g) + O2(g) photooxidation and formation of NO2 reside mostly on titania, while the main functions of the TGA capping agent and the CdTe QDs are associated with the photocatalytic conversion of the generated NO2 to the adsorbed NO x species, significantly boosting the selectivity toward solid-state NO x storage. Reuse experiments showed that photocatalytic performance of the CdTe/P25 system can be preserved to a reasonable extent with only a moderate decrease in the photocatalytic performance. Although some decrease in the photocatalytic activity was observed after aging, CdTe/P25 could still outperform P25 benchmark photocatalyst. Increasing CdTe QDs loading from the currently optimized minuscule concentrations could be a useful strategy to increase further the catalytic lifetime/stability of the CdTe/P25 system with only a minor penalty in catalytic activity.

Integration of Quantum Confinement and Alloy Effect to Modulate Electronic Properties of RhW Nanocrystals for Improved Catalytic Performance toward CO2 Hydrogenation.

The d-band center and surface negative charge density generally determine the adsorption and activation of CO2, thus serving as important descriptors of the catalytic activity toward CO2 hydrogenation. Herein, we engineered the d-band center and negative charge density of Rh-based catalysts by tuning their dimensions and introducing non-noble metals to form an alloy. During the hydrogenation of CO2 into methanol, the catalytic activity of Rh75W25 nanosheets was 5.9, 4.0, and 1.7 times as high as that of Rh nanoparticles, Rh nanosheets, and Rh73W27 nanoparticles, respectively. Mechanistic studies reveal that the remarkable activity of Rh75W25 nanosheets is owing to the integration of quantum confinement and alloy effect. Specifically, the quantum confinement in one dimension shifts up the d-band center of Rh75W25 nanosheets, strengthening the adsorption of CO2. Moreover, the alloy effect not only promotes the activation of CO2 to form CO2δ- but also enhances the adsorption of intermediates to facilitate further hydrogenation of the intermediates into methanol.

Integration of Photothermal Effect and Heat Insulation to Efficiently Reduce Reaction Temperature of CO2 Hydrogenation.

The photothermal effect is applied in CO2 hydrogenation to reduce the reaction temperature under illumination by encapsulating Pt nanocubes and Au nanocages into a zeolitic imidazolate framework (ZIF-8). Under illumination, the heat generated by the photothermal effect of Au nanocages is mainly insulated in the ZIF-8 to form a localized high-temperature region, thereby improving the catalytic activity of Pt nanocubes.

Pt3 Co Octapods as Superior Catalysts of CO2 Hydrogenation.

As the electron transfer to CO2 is a critical step in the activation of CO2 , it is of significant importance to engineer the electronic properties of CO2 hydrogenation catalysts to enhance their activity. Herein, we prepared Pt3 Co nanocrystals with improved catalytic performance towards CO2 hydrogenation to methanol. Pt3 Co octapods, Pt3 Co nanocubes, Pt octapods, and Pt nanocubes were tested, and the Pt3 Co octapods achieved the best catalytic activity. Both the presence of multiple sharp tips and charge transfer between Pt and Co enabled the accumulation of negative charges on the Pt atoms in the vertices of the Pt3 Co octapods. Moreover, infrared reflection absorption spectroscopy confirmed that the high negative charge density at the Pt atoms in the vertices of the Pt3 Co octapods promotes the activation of CO2 and accordingly enhances the catalytic activity.