Emerging therapeutic and diagnostic strategies for coronary artery disease: Current trends and future perspectives.

Coronary vascular disease (CVD) is the general term used to cover conditions like narrowed blood vessels that may cause stroke or heart attack. Coronary artery disease (CAD) is one of the CVD and it is the most severe disease worldwide. The traditional treatment for CAD includes Coronary Artery Bypass Graft Surgery (CABG) and Percutaneous Coronary Intervention (PCI). The evolution of science and technology has led to advancement in the treatment of CAD. Nanoparticles are very suitable for the treatment of CAD by using it as a capsule for targeted drug delivery. Non-coding RNAs like si-RNA and mi-RNA are used as therapeutic agents due to their unique characteristics. In recent years, this si-RNA and miRNA usage in treating diseases has significantly increased. These are used as therapeutic agents for CAD treatment due to their properties like unique mode of action and regulation of gene expression. Another treatment for CAD is stem cells. These are used in CAD treatment because they improve blood supply to the areas where the blood vessels are narrowed down due to atherosclerosis and also, they promote cardiac cell regeneration. These RNA and stem cells are usually encapsulated with nanoparticles to avoid degradation. In this article let us discuss in detail about the treatments of CAD.

Ataxia-Telangiectasia Mutated (ATM) gene signaling pathways in human cancers and their therapeutic implications.

Cancer is a multifaceted disease driven by abnormal cell growth and poses a significant global health threat. The multifactorial causes, differences in individual susceptibility to therapeutic drugs, and induced drug resistance pose major challenges in addressing cancers effectively. One of the most important aspects in making cancers highly heterogeneous in their physiology lies in the genes involved and the changes occurring to some of these genes in malignant conditions. The Genetic factors have been implicated in the oncogenesis, progression, responses to treatment, and metastasis. One such gene that plays a key role in human cancers is the mutated form of the Ataxia-telangiectasia gene (ATM). ATM gene located on chromosome 11q23, plays a vital role in maintaining genomic stability. Understanding the genetic basis of A-T is crucial for diagnosis, management, and treatment. Breast cancer, lung cancer, prostate cancer, and gastric cancer exhibit varying relationships with the ATM gene and influence their pathways. Targeting the ATM pathway proves promising for enhancing treatment effectiveness, especially in conjunction with DNA damage response pathways. Analyzing the therapeutic consequences of ATM mutations, especially in these cancer types facilitates the approaches for early detection, intervention, development of personalized treatment approaches, and improved patient outcomes. This review emphasizes the role of the ATM gene in various cancers, highlighting its impact on DNA repair pathways and therapeutic responses.

Assessment of genome mutation analysis for tumor-informed detection of circulating tumor DNA in patients with breast cancer.

INTRODUCTION: Breast cancer, one of the most aggressive types of cancer, poses significant challenges for diagnosis and treatment. Emerging as a promising biomarker, circulating tumor DNA (ctDNA) can be used to identify and monitor disease risk. This study sought to examine the impact of mutations in various genes on the progression of breast cancer. Genetic variants associated with breast cancer have been examined in individuals diagnosed with the disease worldwide. METHODS: Fifty female participants underwent breast cancer testing. Sanger sequencing was used to analyze peripheral blood DNA from these individuals to detect disease-causing mutations in the BRCA1, BRCA2, PTEN, TP53, and ATM genes. Genetic alterations linked to breast cancer were screened and the findings were compared with those of tumor genes. RESULTS: The development of hereditary/early onset breast cancer in this study was significantly associated with mutations in ATM, PTEN, TP53, and BRCA1/BRCA2, according to the analysis of sequencing data. CONCLUSION: This study demonstrates the feasibility of analyzing ctDNA in patients with breast cancer (BC) undergoing palliative treatment using an SS-based technique.

Extracellular L-Asparaginase Synthesis Bacillus niacin Isolation, Optimization, and Characterization from Marine Saltern Sediment Sources.

Background: Asparagine is an amino acid that can be converted into aspartic acid and ammonia by the enzyme L-asparaginase. Some forms of cancer, such Acute Lymphoblastic Leukaemia (ALL) and Non-Hodgkin Lymphoma (NHL), respond well to this enzyme when employed as a chemotherapeutic drug. The purpose of this research was to find bacteria that can manufacture the enzymes L-asparaginasein marine slattern sediment which can be employed in commercial and industrial scale production. Methods: All of the strains were identified as Bacillus niacini spp. by biochemical and molecular testing. The strain belongs to the Bacillus genus, according to nutritional, biochemical, PCR and 16srRNA sequencing data. Results: According to the findings of this research, Bacillus niacin spp. have the potential to create a substance that is helpful in a variety of medical applications. The results of this study hint to the possibility that bacteria have the ability to produce antimicrobial compounds, which have the potential to be successful in a wide variety of environments. Conclusion: Numerous opportunities may arise for researchers interested in utilizing the medical potential of enzyme-producing bacteria if they are successfully isolated and screened from aquatic and terrestrial habitats.

Implications and progression of peroxiredoxin 2 (PRDX2) in various human diseases.

Peroxiredoxin 2 (PRDX2), a characteristic 2-Cys enzyme is one of the foremost effective scavenger proteins against reactive oxygen species (ROS) and hydrogen peroxide (H2O2) defending cells against oxidative stress. Dysregulation of this antioxidant raises the quantity of ROS and oxidative stress implicated in several diseases. PRDX2 lowers the generation of ROS that takes part in controlling several signalling pathways occurring in neurons, protecting them from stress caused by oxidation and an inflammatory harm. Depending on the aetiological variables, the kind of cancer, and the stage of tumour development, PRDX2 may behave either as an onco-suppressor or a promoter. However, overexpression of PRDX2 may be linked to the development of numerous cancers, including those of the colon, cervix, breast, and prostate. PRDX2 also plays a beneficial effect in inflammatory diseases. PRDX2 being a thiol-specific peroxidase, is known to control proinflammatory reactions. The spilling of PRDX2, on the other hand, accelerates cognitive impairment following a stroke by triggering an inflammatory reflex. PRDX2 expression patterns in vascular cells tend to be crucial to its involvement in cardiovascular diseases. In vascular smooth muscle cells, if the protein tyrosine phosphatase is restricted, PRDX2 could avoid the neointimal thickening which relies on platelet derived growth factor (PDGF), a vital component of vascular remodelling. A proper PRDX2 balance is therefore crucial. The imbalance causes a number of illnesses, including cancers, inflammatory diseases, cardiovascular ailments, and neurological and neurodegenerative problems which are discussed in this review.

Biomarkers and biosensors for early cancer diagnosis, monitoring and prognosis.

Cancers continue to be of major concern due to their serious global socioeconomic impact, apart from the continued increase in the incidence of various cancer types. A major challenge that this disease poses is due to the low "early detection" rates which limit the therapeutic outcomes for the affected individuals. Current research has highlighted the discovering biomarkers that help in early cancer detection and the development of technologies for the detection and quantification of such biomarkers. Biomarkers range from proteins to nucleic acids, and can be specific to a particular cancer type. Detection and quantification of such biomarkers at low levels from biological samples is being made possible by the advent of developing biosensors and by using biomedical engineering technologies such as tumor-on-a-chip models. Here, we present biomarkers that can be helpful for the early detection of breast, colorectal, esophageal, lung, liver, ovarian, and prostate cancer. In addition, we discuss the potential of circulating tumor cell DNA (ctDNA) as an early diagnostic marker. Finally, biosensors available for the detection of cancer biomarkers, which is a recent advancement in this area of research, are discussed.

Deciphering the binding mechanism of an anti-cancer phytochemical plumbagin with calf thymus DNA using biophysical and in silico techniques.

Plumbagin (PLM), a plant derivative, is well known for a wide range of therapeutic effects in humans including anti-cancer, anti-inflammatory, anti-oxidant, and anti-microbial. Cytotoxic and genotoxic potential of this phytochemical has been studied which demands further insight. DNA being a major target for several drugs was taken to study against PLM to understand its effects on the cellular system. UV-Vis spectroscopy has indicated the binding of PLM to ctDNA and dye displacement assays have confirmed the formation of PLM-ctDNA complex. The insignificant changes in circular dichroism spectra suggested that PLM is not affecting the structural makeup of the ctDNA, hence the binding could be peripheral and not intercalating. Further, the relative viscosity and minimal change in melting temperature upon the complex formation supported this finding and confirmed the groove binding of PLM. Molecular docking analysis and simulation studies also show PLM as a minor groove binder to DNA and provide details on the interaction dynamics of PLM-DNA complex. Docking followed by a 100 ns simulation reveals the negative Gibbs free energy change (∆G = -6.6 kcal mol-1), and the formation of a stable complex. The PLM- DNA complex with stable dynamics was further supported by different parameters including RMSD, RMSF, SASA, Rg, and the energy profile of interaction. This study provides an insight into the cytotoxic and genotoxic mechanism of PLM which can be a crucial step forward to exploit its therapeutic potential against several diseases including cancer.

Implications of Toll-like receptors (TLRs) and their signaling mechanisms in human cancers.

Most essential pattern-recognition receptors regulating innate immune functions are toll-like receptors (TLRs). TLRs are characterized by lack of concurrent epithelial markers and are typically identified by their gene expressions. One major mechanism by which TLRs generate their effector functions is by triggering inflammatory responses. Activation of TLRs can impact initiation, advancement, and control of cancers by regulating the inflammatory microenvironment. Several TLRs have been implicated in human cancers and some of them are identified as cancer biomarkers as well; for example, TLRs 2, 3, 5 are expressed more frequently in most cancers. Knowing the upregulation and downregulation of the TLR genes in human cancers will be useful for the development of newer therapeutic targets which can disrupt the pathways associated with such deregulation. We present here the various TLRs and their functions in human lung, gastric, breast, prostate, oral, ovarian, colorectal, cervical, esophageal, bladder and hepatic cancers.

Prospectives of mirna gene signaling pathway in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is one of the destructive breast cancer subtypes which cannot be treated by current therapies, which is characterized by the lack of estrogen (ER), Progesterone (PR), and Human epidermal receptor (HER2). The treatment for this chemotherapy or radiotherapy and surgery are such treatments and also novel biomarkers or treatment targets can quickly require to improve the outcome of the disease. MicroRNAs are the most popular and offer prospects for TNBC diagnosis and therapy. Some of the miRNAs implicated in THBCs are miR-17-5p, miR-221-3p, miR-26a, miR-136-5p, miR-1296, miR-145, miR-4306, miR-508-5p, miR-448, miR-539, miR-211-5p and miR-218. Potential MiRNAs and their signaling pathways that can be utilized for the diagnosis of TNBC are miR-155, miR-182-5p, miR-9-1-5p, miR-200b, miR-200a, miR-429, miR-195, miR-145-5p, miR-506, and miR-22-3p. miRNAs with known functions as tumor suppressors include miR-1-3p, miR-133a-3p, miR-655, miR-206, miR-136, miR-770, miR-148a, miR-197-3p, miR-137, and miR-127-3p. Analysis of genetic biomarkers, such as miRNAs in TNBC, upholds the pertinence in the diagnosis of the disease. The aim of the review was to clarify the different types of miRNAs characters in TNBC. Recent reports suggest an important role of miRNAs in tumor metastasis. We review here the important miRNAs and their signaling pathways implicated in the oncogenesis, progression, and metastasis of TNBCs.

Recent and advanced therapy for oral cancer.

Oral cancer is a common and deadly kind of tissue invasion, has a high death rate, and may induce metastasis that mostly affects adults over the age of 40. Most in vitro traditional methods for studying cancer have included the use of monolayer cell cultures and several animal models. There is a worldwide effort underway to reduce the excessive use of laboratory animals since, although being physiologically adequate, animal models rarely succeed in exactly mimicking human models. 3D culture models have gained great attention in the area of biomedicine because of their capacity to replicate parent tissue. There are many benefits to using a drug delivery approach based on nanoparticles in cancer treatment. Because of this, in vitro test methodologies are crucial for evaluating the efficacy of prospective novel nanoparticle drug delivery systems. This review discusses current advances in the utility of 3D cell culture models including multicellular spheroids, patient-derived explant cultures, organoids, xenografts, 3D bioprinting, and organoid-on-a-chip models. Aspects of nanoparticle-based drug discovery that have utilized 2D and 3D cultures for a better understanding of genes implicated in oral cancers are also included in this review.

Coating of chitosan on poly D,L-lactic-co-glycolic acid thymoquinone nanoparticles enhances the anti-tumor activity in triple-negative breast cancer.

Breast cancer is the second most common cancer around the world. Triple-negative breast cancer (TNBC) is characterized by the absence of three receptors: progesterone, estrogen, and human epidermal growth factor-2 receptor (HER2). Various synthetic chemotherapies have gained attention but they caused unwanted side effects. Therefore, some secondary therapies are now becoming famous against this disease. For instance, natural compounds have been extensively researched against many diseases. However, enzymatic degradation and low solubility remain a major concern. To combat these issues, various nanoparticles have been synthesized and optimized from time to time, which increases its solubility and hence therapeutic potential of a particular drug increases. In this study, we have synthesized Poly D,L-lactic-co-glycolic acid (PLGA) loaded thymoquinone (TQ) nanoparticle (PLGA-TQ-NPs) and then coated them by chitosan (CS) (PLGA-CS-TQ-NPs), which was characterized by different methods. Size of non-coated NPs was 105 nm with PDI value of 0.3 and the size of coated NPs was 125 nm with PDI value of 0.4. Encapsulation efficiency (EE%) and Drug loading (DL%) was found to be 70.5 ± 2.33 and 3.38 for non-coated and 82.3 ± 3.11 and 2.66 for coated NPs respectively. We have also analysed their cell viability against MDA-MB-231 and SUM-149 TNBC cell lines. The resultant, nanoformulations exhibit anti-cancerous activity in a dose and time-dependent manner for MDA-MB-231 and SUM-149 cell lines with an IC50 value of (10.31 ± 1.15, 15.60 ± 1.25, 28.01 ± 1.24) and (23.54 ± 1.24, 22.37 ± 1.25, 35 ± 1.27) for TQ free, PLGA-TQ-NPs and PLGA-CS-TQ-NPs respectively. For the first time, we have developed a nanoformulations of PLGA loaded TQ coated with CS NPs (PLGA-CS-TQ-NPs) against TNBC which led to their enhanced anti-cancerous effects.

Process optimization and antioxidative activity of polyphenols derived from different seaweed species Sargassum Miyabei, Undaria Pinnatifida Suringar, and Sargassum Thunbergii.

The aim of this study was to extract the polyphenols from three major seaweed species such as Sargassum miyabei, Undaria pinnatifida suringar, and Sargassum thunbergii, which are found in the coastal province (Guangdong), a longest coastal line in China. It was found that the Sargassum thunbergii produced more polyphenols (34.99 mg) as compared to Sargassum miyabei (23.26 mg) and Undaria pinnatifida suringar (25.34 mg), respectively. The orthogonal method was used for the extraction of phenolic compounds and extraction condition of each seaweed species was optimized. The antioxidant activity of extracted polyphenols from all three species stated that the polyphenols extracted from Undaria pinnatifida suringar demonstrated the highest antioxidative activity. Furthermore, gas chromatography-mass spectrometry (GC-MS) was used for qualitative analysis of polyphenols, which revealed that the major components of polyphenols extracted from Undaria pinnatifida suringar were gallic acid and arbutin followed by syringate in Sargassum miyabei and phloretin in Sargassum thunbergii.

Targeting Cytotoxin-Associated Antigen A, a Virulent Factor of Helicobacter pylori-Associated Gastric Cancer: Structure-Based In Silico Screening of Natural Compounds.

Gastric cancer is the fifth most frequent cancer and the third major cause of mortality worldwide. Helicobacter pylori, a bacterial infection linked with GC, injects the cytotoxin-associated antigen A (CagA; an oncoprotein) into host cells. When the phosphorylated CagA protein enters the cell, it attaches to other cellular components, interfering with normal cellular signaling pathways. CagA plays an important role in the progression of GC by interacting with phosphatidylserine of the host cell membrane. Therefore, disrupting the CagA-phosphatidylserine connection using small molecules appears to be a promising therapeutic approach. In this report, we screened the natural compounds from ZINC database against the CagA protein using the bioinformatics tools. Hits were initially chosen based on their physicochemical, absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics, as well as other drug-like characteristics. To locate safe and effective hits, the PAINS filter, binding affinities estimation, and interaction analysis were used. Three compounds with high binding affinity and specificity for the CagA binding pocket were discovered. The final hits, ZINC153731, ZINC69482055, and ZINC164387, were found to bind strongly with CagA protein, with binding energies of -11.53, -10.67, and -9.21 kcal/mol, respectively, which were higher than that of the control compound (-7.25 kcal/mol). Further, based on binding affinity and interaction pattern, two leads (ZINC153731, ZINC69482055) were chosen for molecular dynamics (MD) simulation analysis. MD results showed that they displayed stability in their vicinity at 100 ns. This study suggested that these compounds could be used as possible inhibitors of CagA protein in the fight against GC. However, additional benchwork tests are required to validate them as CagA protein inhibitors.

Effect of herbal formulation intake on health indices in albino Wistar rat model.

Dyslipidemia management activity of ginger-, garlic-, and lemon-based herbal mixture was tested as paste and herbal extract in hypercholesterolemic adult male albino rats. Atherogenic diet-induced hypercholesterolemia in rats was treated by supplementing the diet with 2.5% herbal paste (4.2 g/kg b.w.) or 2.5 ml oral gavage (20 ml/kg b.w.) of liquid herbal extract daily for 42 days. Hematological and serological outcomes of herbal formulation feeding were compared with the cholesterol-fed positive control and normal control. The results suggest the significant (p < .05) inhibitory properties of herbal paste and liquid extracts against dyslipidemia showing 31%-37%, 62%-68%, and 40%-56% lower levels of total cholesterol, triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), respectively. Treating cholesterol-fed animals with herbal paste and extract significantly (p < .05) increased total protein (5-5.5 g/dl) and serum albumin (3.7-4.2 g/dl) concentration as compared to the normal control. Contrary to significant hypocholesterolemic activity, higher serum total bilirubin levels, that is, 0.70 mg/dl, were observed in rats subchronically exposed to herbal paste and liquid extracts. Nonsignificant (p > .05) impact of herbal formula feeding was observed on hematological indices except lymphocyte counts, that is, 93% in rats fed on herbal paste. The results validate conventional hypocholesterolemic claims associated with ginger-, garlic-, and lemon-based herbal formulations; however, deeper insight into their dose-dependent response in hypercholesterolemia is necessitated to rule out the toxicological impact on the consumer.

Vaginal Microbiota and HPV Infection: Novel Mechanistic Insights and Therapeutic Strategies.

Cervical cancer is a global public health concern. The complex interaction of genetic and environmental factors is critical for the progress of cervical cancer. Growing evidence suggests that microbes, human papillomavirus (HPV), and the immune system interact closely with each other to govern homeostasis of the vaginal environment and the health of the lower genital tract of females. Certain vaginal microbial strains may play either a protective or a pathogenic role in carcinogenesis of the cervix after HPV persistent infection. Probiotics can therefore present a putative therapeutic approach for cervical cancer. However, work in this field remains limited. Recent technological developments have allowed us to identify microbes and their products using culture-independent molecular detection techniques. In this review, we discuss the composition of the vaginal bacterial community, its commensal flora and the protective impact this has on the health of the female genital tract. This review will also describe critical immune factors in lower genital tract health and summarize the role of the vaginal microbiota in cervical carcinogenesis. Knowledge in this field has provided researchers with the clues and tools to propose the use of probiotics as a potential line of treatment for cervical cancer and has provided valuable insights into host-pathogen interaction dynamics within the female genital tract.

Novel processing techniques and spinach juice: Quality and safety improvements.

In this study, the combined effect of ultrasound (US) and pulsed electric field (PEF) techniques was analyzed for the quality improvement and microbial safety of spinach juice. The spinach juice was treated with US at frequency of 40 kHz, radiating power of 200 W below 30 ± 2 °C temperature for 21 min in ultrasonic bath cleaner, and PEF treatment (pulse frequency: 1 kHz, flow rate: 60 mL/min, temperature: 30 ± 2 °C, time: 335 µs, electric field strength 9 kV/cm) was done. In results, the combined (US-PEF) treatment attained the highest value of minerals and total free amino acids as compared to US or PEF treatment alone. US-PEF treatment significantly reduced the total plate count (3.83 to 1.97 log CFU/mL), E. coli/Coliform (1.90 to 0.75 log CFU/mL) and yeast and mold (4.23 to 2.22 log CFU/mL). Fourier-transform infrared spectroscopy (FT-IR) spectra showed that all nonthermal treatments led to a higher concentration of carbonyl compounds rather generate new carbonyl compounds. US-PEF treatment significantly reduced the particle size. The rheology of spinach juice was drastically changed by all nonthermal techniques, indicating non-Newtonian modal accompanied by a decrease of consistency index (K), apparent viscosity (η), and increase of flow behavior (n). Overall, the improved quality of spinach juice shows the suitability of both technologies for industrial applications despite the variations in rheological properties. PRACTICAL APPLICATION: Nowadays, nonthermal technologies like US and PEF are being used to enhance the nutritional quality and stability of different fruits and vegetable juices. The current research shows that US-PEF application can enhance the free amino acids and mineral contents while significantly decrease microbial activities and particle size. The rheology of spinach juice can be dramatically changed, through the reduction of consistency index (K), apparent viscosity (η) and elevation of flow behavior (n). The results of this research proposed that US-PEF treatment can be a more suitable nonthermal application to enhance the quality of spinach juice at an industrial scale.

Novel extraction techniques and pharmaceutical activities of luteolin and its derivatives.

Luteolin is a 3', 4', 5, 7 tetra hydroxyl flavonoid that exits in many plants, fruits, and vegetable. Many methods of extraction, isolation, and purification are being used, and therapeutic properties are being under discussion due to its valuable role in nutrition and human health. In this review, we have summarized conventional and novel extraction techniques from most recent research on luteolin, its derivatives, and its biological activities. Maceration, soxhlet, reflux, hydrodistillation, ultrasound-assisted extraction, microwave-assisted extraction, ultrasound microwave-assisted extraction, enzyme-assisted extraction, supercritical fluid extraction, and high-speed counter-current chromatography extraction techniques are being used for isolation and purification of these phytochemicals. The anti-inflammatory, anti-cancer, antioxidant, antiviral, heart protective, neurological impairments protection, anti-aging, and whiting properties have been discussed in this review. The literature suggests luteolin and its derivative has many promising health benefits and its therapeutic activity is strongly associated with isolating and purifying solvents and extraction techniques. PRACTICAL APPLICATIONS: This review aims to highlight the sources, novel extraction techniques, and pharmaceutical properties of luteolin. This review provides enough knowledge about how to get maximum extraction yield of luteolin using the novel extraction techniques. Because its therapeutic activity is strongly associated with isolating and purifying solvents and techniques.