Harmful Free Radicals in Aging: A Narrative Review of Their Detrimental Effects on Health.

The production of harmful free radicals (H-FRs), especially those with oxygen or nitrogen atoms, depends on both internal and environmental causes. The negative effects of H-FRs are greatly alleviated by antioxidant protection. The harmful impact of oxidative stress, or OS, is brought on by a disparity between the defense mechanisms of the body and the creation of H-FRs. Aging is characterized by a slow decline in tissue and organ competence. Age-mediated pathologies start as an aberrant accumulation of H-FRs, which inhibit cells' capacity to divide, repair, and operate, based on the OS theorem of aging. The natural outcome of this situation is apoptosis. These conditions may include skeletal muscle dysfunction, cancer, cardiovascular, chronic hepatitis, chronic renal, and chronic pulmonary disorders. Given the substantial role that OS plays in the progression of many of these illnesses, antioxidant-based therapy may have a favorable impact on how these diseases progress. To ascertain the true efficacy of this therapy strategy, more research is necessary. The aim of this study is to provide an overview of the literature on this challenging issue that is attracting interest.

Unveiling The Biomedical Applications Of Novel Coumarins Isolated From Capsicum Annuum L. Seeds By A Multivariate Extraction Technique.

For the first time, kinetic thermomagnetic extraction is a novel approach presented in this work. It required the application of four distinct variables: rotation speed (50, 75, and 100 rpm), magnetic field (0.8, 1.2, and 1.6 T), time interval (30, 60, and 90 min), and temperature (45, 55, and 65°C). Numerous phytochemical categories were detected in the 81 crude chloroform extracts of green sweet bell pepper seeds that were collected, according to phytochemical analysis. Nine extracts were discovered to be linked to the coumarin chemical class and to have the same two extraction parameters: a 90-minute extraction duration and a 55°C extraction temperature. To enable their coumarin contents to be chemically separated and chromatographically purified, two of these extracts containing coumarin were chosen. Four new phytocoumarins have been identified and their molecular structures distinguished using FTIR spectra, 1H-NMR, 13C-NMR, and mass analysis. The results demonstrated that the extracted phytocoumarins have exceptional oxidative stress-mitigating characteristics, ranging from 71.51 to 81.48%, when compared to a positive control. Furthermore, they showed excellent cytotoxicity against the test malignant populations (IC50 values of 46.76-81.45 µg/ml). The isolates need to be taken into account as dual COX-2/5-LOX antagonists because they also showed a selective anti-inflammatory effect.

Plant-Derived Coumarins: A Narrative Review Of Their Structural And Biomedical Diversity.

Plant-derived coumarin (PDC) is a naturally occurring heterocyclic backbone that belongs to the benzopyrone family. PDC and its based products are characterized by low toxicity and high distribution in a variety of herbal treatments that have numerous therapeutic potentials. These include anticoagulants, antibacterials, anti-inflammatory agents, anticancer agents, antioxidants, and others. So, it may be appropriate to investigate the qualities and potential bioactivities of PDCs. This article provides an overview of the biomedical potentials, availability, and clinical use possibilities of PDCs, with a focus on their important modes of action, using information on various pharmacological qualities discovered. The data used in this study came from published research between 2015 and 2023. We reviewed a selection of databases, including PubMed, Scopus, Web of Science, and Google Scholar, during that period. In conclusion, because of their abundance in medicinal plants, the clinical biochemistry attributes of PDCs are currently of interest. In a variety of medical specialties, PDCs serve a useful role as therapeutic agents.

Natural linear coumarin-heterocyclic conjugates: A review of their roles in phytotherapy.

Heterocycle conjugates provide a fresh investigative scope to find novel molecules with enhanced phytotherapeutic characteristics. Coumarin-based products are widely used in the synthesis of several compounds with biological and medicinal properties since they are naturally occurring heterocycles with a broad dispersion. The investigation of coumarin-based phytochemicals with annulated heterocyclic rings is a promising approach to discovering novel conjugates with significant phytotherapeutic attributes. Due to the applicable coumarin extraction processes, a range of linear coumarin-heterocyclic conjugates were isolated from different natural resources and exhibited remarkable therapeutic efficacy. This review highlights the phytotherapeutic potential and origins of various natural linear coumarin-heterocyclic conjugates. We searched several databases, including Science Direct, Web of Science, Springer, Google Scholar, and PubMed. After sieving, we ultimately identified and included 118 pertinent studies published between 2000 and the middle of 2023. This will inspire medicinal chemists with extremely insightful ideas for designing and synthesizing therapeutically active lead compounds in the future that are built on the pharmacophores of coumarin-heterocyclic conjugates and have significant therapeutic attributes.

Integrating of analytical techniques with enzyme-mimicking nanomaterials for the fabrication of microfluidic systems for biomedical analysis.

Bioanalysis faces challenges in achieving fast, reliable, and point-of-care (POC) determination methods for timely diagnosis and prognosis of diseases. POC devices often display lower sensitivity compared to laboratory-based methods, limiting their ability to quantify low concentrations of target analytes. To enhance sensitivity, the synthesis of new materials and improvement of the efficiency of the analytical strategies are necessary. Enzyme-mimicking materials have revolutionized the field of the fabrication of new high-throughput sensing devices. The integration of microfluidic chips with analytical techniques offers several benefits, such as easy miniaturization, need for low biological sample volume, etc., while also enhancing the sensitivity of the probe. The use enzyme-like nanomaterials in microfluidic systems can offer portable strategies for real-time and reliable detection of biological agents. Colorimetry and electrochemical methods are commonly utilized in the fabrication of nanozyme-based microfluidic systems. The review summarizes recent developments in enzyme-mimicking materials-integrated microfluidic analytical methods in biomedical analysis and discusses the current challenges, advantages, and potential future directions.

Nucleic acid-based vaccine for ovarian cancer cells; bench to bedside.

Ovarian cancer continues to be a difficult medical issue that affects millions of individuals worldwide. Important platforms for cancer immunotherapy include checkpoint inhibitors, chimeric antigen receptor T cells, bispecific antibodies, cancer vaccines, and other cell-based treatments. To avoid numerous infectious illnesses, conventional vaccinations based on synthetic peptides, recombinant subunit vaccines, and live attenuated and inactivated pathogens are frequently utilized. Vaccine manufacturing processes, however, are not entirely safe and carry a significant danger of contaminating living microorganisms. As a result, the creation of substitute vaccinations is required for both viral and noninfectious illnesses, including cancer. Recently, there has been testing of nucleic acid vaccines, or NAVs, as a cancer therapeutic. Tumor antigens (TAs) are genetically encoded by DNA and mRNA vaccines, which the host uses to trigger immune responses against ovarian cancer cells that exhibit the TAs. Despite being straightforward, safe, and easy to produce, NAVs are not currently thought to be an ideal replacement for peptide vaccines. Some obstacles to this strategy include selecting the appropriate therapeutic agents (TAs), inadequate immunogenicity, and the immunosuppressive characteristic of ovarian cancer. We focus on strategies that have been employed to increase NAVs' effectiveness in the fight against ovarian cancer in this review.

Therapeutic gene delivery by mesenchymal stem cell for brain ischemia damage: Focus on molecular mechanisms in ischemic stroke.

Cerebral ischemic damage is prevalent and the second highest cause of death globally across patient populations; it is as a substantial reason of morbidity and mortality. Mesenchymal stromal cells (MSCs) have garnered significant interest as a potential treatment for cerebral ischemic damage, as shown in ischemic stroke, because of their potent intrinsic features, which include self-regeneration, immunomodulation, and multi-potency. Additionally, MSCs are easily obtained, isolated, and cultured. Despite this, there are a number of obstacles that hinder the effectiveness of MSC-based treatment, such as adverse microenvironmental conditions both in vivo and in vitro. To overcome these obstacles, the naïve MSC has undergone a number of modification processes to enhance its innate therapeutic qualities. Genetic modification and preconditioning modification (with medications, growth factors, and other substances) are the two main categories into which these modification techniques can be separated. This field has advanced significantly and is still attracting attention and innovation. We examine these cutting-edge methods for preserving and even improving the natural biological functions and therapeutic potential of MSCs in relation to adhesion, migration, homing to the target site, survival, and delayed premature senescence. We address the use of genetically altered MSC in stroke-induced damage. Future strategies for improving the therapeutic result and addressing the difficulties associated with MSC modification are also discussed.

Long non-coding RNA (lncRNA) PVT1 in drug resistance of cancers: Focus on pathological mechanisms.

According to estimates, cancer will be the leading cause of death globally in 2022, accounting for 9.6 million deaths. At present, the three main therapeutic modalities utilized to treat cancer are radiation therapy, chemotherapy, and surgery. However, during treatment, tumor cells resistant to chemotherapy may arise. Drug resistance remains a major oppose since it often leads to therapeutic failure. Furthermore, the term "acquired drug resistance" describes the situation where tumor cells already display drug resistance before undergoing chemotherapy. However, little is still known about the basic mechanisms underlying chemotherapy-induced drug resistance. The development of new technologies and bioinformatics has led to the discovery of additional genes associated with drug resistance. Long noncoding RNA plasmacytoma variant translocation 1 (PVT1) has been linked to an increased risk of cancer, according to a growing body of research. Apart from biological functions associated with cell division, development, pluripotency, and cell cycle, lncRNA PVT1 contributes significantly to the regulation of various aspects of genome function, such as transcription, splicing, and epigenetics. The article will address the mechanism by which lncRNA PVT1 influences drug resistance in cancer cells.

Overcoming drug resistance with specific nano scales to targeted therapy: Focused on metastatic cancers.

Metastatic cancer, which accounts for the majority of cancer fatalities, is a difficult illness to treat. Currently used cancer treatments include radiation therapy, chemotherapy, surgery, and targeted treatment (immune, gene, and hormonal). The disadvantages of these treatments include a high risk of tumor recurrence and surgical complications that may result in permanent deformities. On the other hand, most chemotherapy drugs are small molecules, which usually have unfavorable side effects, low absorption, poor selectivity, and multi-drug resistance. Anticancer drugs can be delivered precisely to the cancer spot by encapsulating them to reduce side effects. Stimuli-responsive nanocarriers can be used for drug release at cancer sites and provide target-specific delivery. As previously stated, metastasis is the primary cause of cancer-related mortality. We have evaluated the usage of nano-medications in the treatment of some metastatic tumors.

Evaluation of telomere length, reactive oxygen species, and apoptosis in spermatozoa of patients with oligospermia.

50% of cases of infertility are caused by male factor, which acquired or congenital problems may bring on. Male infertility can be caused by oligospermia and asthenozoospermia, which are common. Since the same mutations that cause azoospermia in some people also cause oligozoospermia in others, oligozoospermia may be thought of as a less severe form of azoospermia. Studies have demonstrated telomere length, catalase activity, super oxide dismutase (SOD), and DNA fragmentation can be influential factors for male infertility. The amount of apoptosis, oxidative stress factors, telomere length, and DNA fragmentation were some aspects of healthy sperm that we chose to look into in this study and compare to oligospermia individuals. Oligospermia patients (n = 24) and fertile men (n = 27) semen samples were collected, and the apoptosis rate of sperms in both groups was analyzed (Flow cytometry). Also, gene expression of apoptotic and antiapoptotic markers and telomere length were examined (real-time polymerase chain reaction). The sperm DNA fragmentation kit was used to determine DNA fragmentation and to evaluate catalase and SOD activity; the specific kits and methods were utilized. Higher expression levels of caspase3 (p = .0042), caspase8 (p = .0145), caspase9 (p = .0275), and BAX (p = .0202) mRNA were observed in patients who had oligospermia. In contrast, lower mRNA expression of BCL-2 (p = .0009) was detected in this group. In addition, telomere length was decreased in the oligospermia group (p < .0001) compared to the health group. Moreover, the frequency of apoptosis is induced in patients (p = .0026). The catalase activity is low (p = .0008), but the SOD activity is high (p = .0015) in the patient group. As a result of our findings, we may list the sperm cell apoptosis rate, telomere length, the degree of sperm DNA fragmentation, and lastly, the measurement of significant and efficient oxidative stress markers like SOD and catalase in semen plasma among the principal diagnostic characteristics for oligospermia. Future studies will be better able to treat oligospermia by showing whether these indicators are rising or falling.

Recent advances in mRNA-based vaccine for cancer therapy; bench to bedside.

The messenger RNA (mRNA) vaccines have progressed from a theoretical concept to a clinical reality over the last few decades. Compared to conventional vaccination methods, these vaccines have a number of benefits, such as substantial potency, rapid growth, inexpensive production, and safe administration. Nevertheless, their usefulness was restricted up to now due to worries about the erratic and ineffective circulation of mRNA in vivo. Thankfully, these worries have largely been allayed by recent technological developments, which have led to the creation of multiple mRNA vaccination platforms for cancer and viral infections. The mRNA vaccines have been demonstrated as a powerful alternative to traditional conventional vaccines because of their high potency, safety and efficacy, capacity for rapid clinical development, and potential for rapid, low-cost manufacturing. The paper will examine the present status of mRNA vaccine technology and suggest future paths for the advancement and application of this exciting vaccine platform as a common therapeutic choice.

Role of genetically engineered mesenchymal stem cell exosomes and LncRNAs in respiratory diseases treatment.

The term acute respiratory disease encompasses a wide range of acute lung diseases, which in recent years have been ranked among the top three deadly diseases in the world. Since conventional treatment methods, including the use of anti-inflammatory drugs, have had no significant effect on the treatment process of these diseases, the attention of the medical community has been drawn to alternative methods. Mesenchymal stem cells (MSC) are multipotential stem/progenitor cells that have extensive immunomodulatory and anti-inflammatory properties and also play a critical role in the microenvironment of injured tissue. MSC secretomes (containing large extracellular vesicles, microvesicles, and exosomes) are a newly introduced option for cell-free therapies that can circumvent the hurdles of cell-based therapies while maintaining the therapeutic role of MSC themselves. The therapeutic capabilities of MSCs have been showed in many acute respiratory diseases, including chronic respiratory disease (CRD), novel coronavirus 2019 (COVID -19), and pneumonia. MSCs offer novel therapeutic approaches for chronic and acute lung diseases due to their anti-inflammatory and immunomodulatory properties. In this review, we summarize the current evidence on the efficacy and safety of MSC-derived products in preclinical models of lung diseases and highlight the biologically active compounds present in the MSC secretome and their mechanisms involved in anti-inflammatory activity and tissue regeneration.

The role of exo-miRNA in diagnosis and treatment of cancers, focusing on effective miRNAs in colorectal cancer.

Small extracellular (EV) particles known as exosomes are released by a variety of cell types, including immune system cells, stem cells, and tumor cells. They are regarded as a subgroup of EVs and have a diameter that ranges from 30 to 150 nm. Proteins, lipids, nucleic acids (including RNA and DNA), and different bioactive compounds are among the wide range of biomolecules that make up the cargo of exosomes. Exosomes are crucial for intercellular communication because they let cells share information and signaling chemicals. They are involved in various physiological and pathological processes, including immune responses, tissue regeneration, cancer progression, and neurodegenerative diseases. In conclusion, it is essential to continue research into exosome-based cancer medicines to advance understanding, improve treatment plans, create personalized tactics, ensure safety, and speed up clinical translation.

Isothermal amplification methods in cancer-related miRNA detection; a new paradigm in study of cancer pathology.

MicroRNAs (miRNAs) are short, non-coding RNA molecules that regulate gene expression. They are involved in a wide range of biological processes, including development, differentiation, cell cycle regulation, and response to stress. Numerous studies have demonstrated that miRNAs are present in different bodily fluids, which could serve as an important biomarker. The advancement of techniques and strategies for the identification of cancer-associated miRNAs in human specimens offers a novel opportunity to diagnose cancer in early stages, predict patient prognosis and evaluate response to treatment. Isothermal techniques including loop-mediated isothermal amplification (LAMP), rolling circle amplification (RCA), or recombinase polymerase amplification (RPA) offer simplicity, efficiency, and rapidity in miRNA detection processes. In contrast to traditional PCR (polymerase chain reaction), these techniques analysis and quantify miRNA molecules in specimens using a single constant temperature. In this comprehensive review, we summarized the recent advances in cancer-related miRNA detection via highly sensitive isothermal amplification methods by more focusing on the involved mechanism.

COX 2-inhibitors; a thorough and updated survey into combinational therapies in cancers.

Cyclooxygenase (COX) enzymes are pivotal in inflammation and cancer development. COX-2, in particular, has been implicated in tumor growth, angiogenesis, and immune evasion. Recently, COX-2 inhibitors have arisen as potential therapeutic agents in cancer treatment. In addition, combining COX inhibitors with other treatment modalities has demonstrated the potential to improve therapeutic efficacy. This review aims to investigate the effects of COX inhibition, both alone and in combination with other methods, on signaling pathways and carcinogenesis in various cancers. In this study, a literature search of all major academic databases was conducted (PubMed, Scholar google), including the leading research on the mechanisms of COX-2, COX-2 inhibitors, monotherapy with COX-2 inhibitors, and combining COX-2-inhibitors with chemotherapeutic agents in tumors. The study encompasses preclinical and clinical evidence, highlighting the positive findings and the potential implications for clinical practice. According to preclinical studies, multiple signaling pathways implicated in tumor cell proliferation, survival, invasion, and metastasis can be suppressed by inhibiting COX. In addition, combining COX inhibitors with chemotherapy drugs, targeted therapies, immunotherapies, and miRNA-based approaches has enhanced anti-tumor activity. These results suggest that combination therapy has the potential to overcome resistance mechanisms and improve treatment outcomes. However, caution must be exercised when selecting and administering combination regimens. Not all combinations of COX-2 inhibitors with other drugs result in synergistic effects; some may even have unfavorable interactions. Therefore, personalized approaches that consider the specific characteristics of the cancer and the medications involved are crucial for optimizing therapeutic strategies. In conclusion, as monotherapy or combined with other methods, COX inhibition bears promise in modulating signaling pathways and inhibiting carcinogenesis in various cancers. Additional studies and well-designed clinical trials are required to completely elucidate the efficacy of COX inhibition and combination therapy in enhancing cancer treatment outcomes. This narrative review study provides a detailed summary of COX-2 monotherapy and combination targeted therapy in cancer treatment.

Effective extracellular vesicles in glioma: Focusing on effective ncRNA exosomes and immunotherapy methods for treatment.

This comprehensive article explores the complex field of glioma treatment, with a focus on the important roles of non-coding RNAsRNAs (ncRNAs) and exosomes, as well as the potential synergies of immunotherapy. The investigation begins by examining the various functions of ncRNAs and their involvement in glioma pathogenesis, progression, and as potential diagnostic biomarkers. Special attention is given to exosomes as carriers of ncRNAs and their intricate dynamics within the tumor microenvironment. The exploration extends to immunotherapy methods, analyzing their mechanisms and clinical implications in the treatment of glioma. By synthesizing these components, the article aims to provide a comprehensive understanding of how ncRNAs, exosomes, and immunotherapy interact, offering valuable insights into the evolving landscape of glioma research and therapeutic strategies.

lncRNA-microRNA axis in cancer drug resistance: particular focus on signaling pathways.

Cancer drug resistance remains a formidable challenge in modern oncology, necessitating innovative therapeutic strategies. The convergence of intricate regulatory networks involving long non-coding RNAs, microRNAs, and pivotal signaling pathways has emerged as a crucial determinant of drug resistance. This review underscores the multifaceted roles of lncRNAs and miRNAs in orchestrating gene expression and cellular processes, mainly focusing on their interactions with specific signaling pathways. Dysregulation of these networks leads to the acquisition of drug resistance, dampening the efficacy of conventional treatments. The review highlights the potential therapeutic avenues unlocked by targeting these non-coding RNAs. Developing specific inhibitors or mimics for lncRNAs and miRNAs, alone or in combination with conventional chemotherapy, emerges as a promising strategy. In addition, epigenetic modulators, immunotherapies, and personalized medicine present exciting prospects in tackling drug resistance. While substantial progress has been made, challenges, including target validation and safety assessment, remain. The review emphasizes the need for continued research to overcome these hurdles and underscores the transformative potential of lncRNA-miRNA interplay in revolutionizing cancer therapy.

The mechanistic role of NAT10 in cancer: Unraveling the enigmatic web of oncogenic signaling.

N-acetyltransferase 10 (NAT10), a versatile enzyme, has gained considerable attention as a significant player in the complex realm of cancer biology. Its enigmatic role in tumorigenesis extends across a wide array of cellular processes, impacting cell growth, differentiation, survival, and genomic stability. Within the intricate network of oncogenic signaling, NAT10 emerges as a crucial agent in multiple cancer types, such as breast, lung, colorectal, and leukemia. This compelling research addresses the intricate complexity of the mechanistic role of NAT10 in cancer development. By elucidating its active participation in essential physiological processes, we investigate the regulatory role of NAT10 in cell cycle checkpoints, coordination of chromatin remodeling, and detailed modulation of the delicate balance between apoptosis and cell survival. Perturbations in NAT10 expression and function have been linked to oncogenesis, metastasis, and drug resistance in a variety of cancer types. Furthermore, the bewildering interactions between NAT10 and key oncogenic factors, such as p53 and c-Myc, are deciphered, providing profound insights into the molecular underpinnings of cancer pathogenesis. Equally intriguing, the paradoxical role of NAT10 as a potential tumor suppressor or oncogene is influenced by context-dependent factors and the cellular microenvironment. This study explores the fascinating interplay of genetic changes, epigenetic changes, and post-translational modifications that shape the dual character of NAT10, revealing the delicate balance between cancer initiation and suppression. Taken together, this overview delves deeply into the enigmatic role of NAT10 in cancer, elucidating its multifaceted roles and its complex interplay with oncogenic networks.

Kidney stones: natural remedies and lifestyle modifications to alleviate their burden.

BACKGROUND: Kidney stones (KSs), in fact, have been considered one of the most ancient and prevalent medical conditions that impact a significant number of human beings all around the world. Such stones can range greatly in size and can be detected in any part of the urinary system, including the kidneys, ureters, or bladder itself. The development of stones is caused by the mineral's crystallization, which then interacts with each other and adheres together. Kidney stone formation can represent a prime medical condition for which there are numerous therapies available, among them natural ones. Recurrence of stones after curing is very common, and strategies available to prevent their reoccurrence or even their development for the first time are numerous, with enhanced fluid consumption or avoiding dehydration being the most important one. OBJECTIVE: The current review article aims to draw attention to the potential of natural remedies besides lifestyle modification in the management and prevention of KSs. This is not arbitrary but based on real, documented scientific evidence. METHOD: The natural remedies mentioned in the context of this manuscript were chosen for their availability in almost all nations, or perhaps even in every home. RESULTS: The findings of the present article are very promising and exhibit the potential benefit of natural remedies in addition to shifting to a healthy lifestyle in both the treatment and prevention of KSs.

A glimpse into let-7e roles in human disorders; friend or foe?

MicroRNAs (miRNAs) have been linked to abnormal expression and regulation in a number of diseases, including cancer. Recent studies have concentrated on miRNA Let-7e's significance in precision medicine for cancer screening and diagnosis as well as its prognostic and therapeutic potential. Differential let-7e levels in bodily fluids have the possibility to enable early detection of cancer utilizing less-invasive techniques, reducing biopsy-related risks. Although Let-7e miRNAs have been described as tumor suppressors, it is crucial to note that there exists proof to support their oncogenic activity in vitro and in in vivo. Let-7e's significance in chemo- and radiation treatment decisions has also been demonstrated. Let-7e can also prevent the synthesis of proinflammatory cytokines in a number of degenerative disorders, including musculoskeletal and neurological conditions. For the first time, an overview of the significance of let-7e in the prevention, detection, and therapy of cancer and other conditions has been given in the current review. Additionally, we focused on the specific molecular processes that underlie the actions of let-7e, more particularly, on malignant cells.