Mechanistic Review Research Articles

PO0416: High Dose Rate Salvage Brachytherapy for Prostate Fossa Recurrence: A Mechanistic Review and Preliminary Report of Outcomes

PO0416: High Dose Rate Salvage Brachytherapy for Prostate Fossa Recurrence: A Mechanistic Review and Preliminary Report of Outcomes

Therapeutic opportunities in targeting the protective arm of the renin-angiotensin system to improve insulin sensitivity: a mechanistic review.

In recent years, the knowledge of the physiological and pathophysiological roles of the renin-angiotensin system (RAS) in glucose metabolism has advanced significantly. It is now well-established that blockade of the angiotensin AT1 receptor (AT1R) improves insulin sensitivity. Activation of the AT2 receptor (AT2R) and the MAS receptor are significant contributors to this beneficial effect. Elevated availability of angiotensin (Ang) II) for interaction with the AT2R and increased Ang-(1-7) formation during AT1R blockade mediate these effects. The ongoing development of selective AT2R agonists, such as compound 21 and the novel Ang III peptidomimetics, has significantly advanced the exploration of the role of AT2R in metabolism and its potential as a therapeutic target. These agents show promise, particularly when RAS inhibition is contraindicated. Additionally, other RAS peptides, including Ang IV, des-Asp-Ang I, Ang-(1-9), and alamandine, hold therapeutic capability for addressing metabolic disturbances linked to type 2 diabetes. The possibility of AT2R heteromerization with either AT1R or MAS receptor offers an exciting area for future research, particularly concerning therapeutic strategies to improve glycemic control. This review focuses on therapeutic opportunities to improve insulin sensitivity, taking advantage of the protective arm of the RAS.

Biological Control of Anthracnose in Capsicum annuum Using Inoculants in Hydroponics: A Mechanistic Review

The Colletotrichum species that causes anthracnose poses a significant threat to the growth of Capsicum annuum, or ringer pepper, resulting in significant yield losses. Conventional produced control systems can give rise to ecological and economic difficulties, necessitating the need for alternative, workable solutions. This study explores the feasibility and parts of natural inoculants in controlling anthracnose ailment in Capsicum annuum filled in chipped away at hydroponics structures. As organic inoculants, we utilized a wide variety of useful microorganisms, such as Trichoderma harzianum, Bacillus subtilis, and mycorrhizal parasites. At various stages of the Capsicum annuum plant's development, these inoculants were incorporated into the supplement arrangements for tank farming. Anthracnose was observed and compared to untreated controls and synthetically treated plants in terms of its severity. Plants treated with natural inoculants show a significant reduction in sickness rate and severity, as shown by our findings. In fact, Trichoderma harzianum outperformed Bacillus subtilis and mycorrhizal parasites in terms of biocontrol productivity. Through a series of biochemical and sub-atomic tests, the fundamental instruments were examined. Natural inoculants, according to important discoveries, increase the plant's intrinsic safe reaction by causing fundamental obstruction. This is affirmed by the upregulation of pathogenesis-related (PR) characteristics and extended activity of shield impetuses like peroxidase (Unit), polyphenol oxidase (PPO), and phenylalanine antacid lyase (Amigo). In addition, the inoculants improved root development and supplement absorption, enhancing overall establish health and resistance to microorganisms. This study demonstrates that natural inoculants can be a reasonable and effective method for controlling anthracnose in Capsicum annuum grown in improved tank farms. In accordance with the goals of a potential agribusiness, incorporating these biocontrol specialists into aquafarming frameworks can increase crop productivity and reduce the use of compound pesticides.

A Mechanistic Review on Protective Effects of Mangosteen and its Xanthones Against Hazardous Materials and Toxins.

Due to its pharmacological properties, α-Mangostin, mainly found in Garcinia mangostana (G. mangostana) L. (Mangosteen, queen of fruits), treats wounds, skin infections, and many other disorders. In fact, α-Mangostin and other xanthonoid, including β-Mangostin and γ-Mangostin, are found in G. mangostana, which have various advantages, namely neuroprotective, anti-proliferative, antinociceptive, antioxidant, pro-apoptotic, anti-obesity, anti-inflammatory, and hypoglycemic through multiple signaling mechanisms, for instance, extracellular signal-regulated kinase1/2 (ERK 1/2), mitogenactivated Protein kinase (MAPK), nuclear factor-kappa B (NF-kB), transforming growth factor beta1 (TGF-β1) and AMP-activated protein kinase (AMPK). This review presents comprehensive information on Mangosteen's pharmacological and antitoxic aspects and its xanthones against various natural and chemical toxins. Because of the insufficient clinical study, we hope the current research can benefit from performing clinical and preclinical studies against different toxic agents.

Investigating the protective properties of Panax ginseng and its constituents against biotoxins and metal toxicity: a mechanistic review.

Natural toxins are toxic substances produced by living microorganisms and cause harmful effects to other creatures, but not the organisms themselves. Based on the sources, they are classified into fungal, microbial, herbal, algae, and animal biotoxins. Metals, the oldest toxicants, are not created or destroyed by human industry as elements, just concentrated in the biosphere. An antidote can counteract the toxic effects of a drug or toxin or mitigate the adverse effects of a harmful substance. The potential antidote effects of Panax ginseng in organ toxicity have been proved by many scientific research projects. Herein, we are going to gather a comprehensive mechanistic review of the antidotal effects of ginseng and its main constituents against natural toxins and metal toxicity. In this regard, a literate search has been done in PubMed/Medline, Science Direct, and Scopus from 2000 until 2024. The gathered data showed the protective impacts of this golden plant and its secondary metabolites against aflatoxin, deoxynivalenol, three-nitro propionic acid, ochratoxin A, lipopolysaccharide, nicotine, aconite, domoic acid, α-synuclein, amyloid β, and glutamate as well as aluminum, cadmium, chrome, copper, iron, and lead. These antidotal effects occur by multi-functional mechanisms. It may be attributed to antioxidant, anti-inflammatory, and anti-apoptotic effects. Future research directions on the antidotal effects of ginseng against natural toxins and metal toxicity involve broadening the scope of studies to include a wider range of toxins and metals, exploring synergistic interactions with other natural compounds, and conducting more human clinical trials to validate the efficacy and safety of ginseng-based treatments.

Promising Influences of Moringa oleifera in Functional Foods against Metabolic Syndrome: A Comprehensive and Mechanistic Review.

Metabolic syndrome (MetS) is now considered a global issue with a growing financial and health impact. Numerous herbal alternatives have been examined and researched due to the ever-increasing demand for new medications to treat metabolic syndrome disorders. People have empirically employed Moringa oleifera (MO), a native plant to several Asian nations, for a variety of diseases. We sought to examine recent research on MO in MetS and its potential mechanism of action in the current review. Four databases, including PubMed, Scopus, Web of Sciences, and Google Scholar, were thoroughly searched, and the data were then compiled. In total, 146 papers covering nonclinical and clinical MO investigations in metabolic syndromerelated disorders are included in this study. Numerous research confirmed MO's positive impact on the control of blood glucose, blood pressure, hyperlipidemia, and obesity. Many molecular processes have been investigated, including increasing glucose transporter type 4 (GLUT4) expression, inhibition of β-Hydroxy-β-methylglutaryl-coenzyme A (HMG-CoA), α-glucosidase inhibiting, AMP-activated protein kinase (AMPK) activation, and other suggested mechanisms. The current review established much data favoring MO's potential advantages in metabolic syndrome. However, further research involving human studies is required in this area to determine whether Moringa can effectively treat metabolic syndrome.

Saffron and its major constituents against neurodegenerative diseases: A mechanistic review

BackgroundNeurodegeneration has been recognized as the main pathophysiological alteration in the majority of brain-related diseases. Despite contemporary attempts to provide acceptable medicinal therapies, the conclusion has not been much beneficial. Besides, the complex pathophysiological mechanisms behind neurodegenerative diseases (NDDs) urge the needs for finding novel multi-target agents. Accordingly, saffron with major active constituents and as multi-targeting agents have shown beneficial effects in modulating NDDs with higher efficacy and lower side effects. PurposeThe present study provides a systematic and comprehensive review of the existing in vitro, in vivo, and clinical data on the effectiveness, and signaling pathways of saffron and its key phytochemical components in the management of NDDs. The need to develop novel saffron delivery systems is also considered. MethodsStudies were identified through systematic and comprehensive searches in Science Direct, PubMed, and Scopus databases through April 30, 2024. The whole saffron major constituents (e.g., saffron, crocin, crocetin, picrocrocin, and safranal) and NDDs (e.g., neuro*, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, Huntington*, Parkinson*, Alzheimer*, and brain) were selected as keywords to find related studies. In the systematic analysis, 64 articles were directly included in the current study. Additional reports were added within a comprehensive review. ResultsSaffron and its active metabolites crocin, crocetin, safranal, and picrocrocin have shown acceptable efficacy in managing NDDs like Alzheimer's disease, Parkinson's disease, Attention deficit hyperactivity disorder, depression, and other NDDs via modulating apoptotic (e.g., caspases, Bax/Bcl-2, cytochrome c, and death receptors), inflammatory (e.g., NF-κB, IL-1β, IL-6, TNF-α, and COX-2), and oxidative strass (e.g., Nrf2, GSH, GPx, CAT, SOD, MDA, ROS, and nitrite) signaling pathways. The presented in vitro, in vivo, and clinical evidences showed us a better future of controlling NDDs with higher efficacy, while decreasing associated side effects with no significant toxicity. Additionally, employing novel delivery systems could increase the efficacy of saffron phytoconstituents to resolve the issues pharmacokinetic limitations. ConclusionSaffron and its major constituents employ anti-inflammatory, anti-apoptotic and antioxidant mechanisms in modulating several dysregulated-signaling pathways in NDDs. However, further research is necessary to elucidate the precise underlying mechanisms in exploring the feasibility of using saffron active compounds against NDDs. More studies should focus on dose-response relationships, long-term effects, highlighting key mechanisms, and designing more well-controlled clinical trials. Additionally, developing stable and cost-benefit novel delivery systems in future works helps to remove the pharmacokinetic limitations of saffron major constituents.

Microproteins/micropeptides dysregulation contributes to cancer progression and development: A mechanistic review.

Microproteins, known as micropeptides, are small protein molecules encoded by short open reading frames. These recently identified molecules have been proven to be an essential part of the human proteome that participates in multiple processes, such as DNA repair, mitochondrial respiration, and regulating different signaling pathways. A growing body of studies has evidenced that microproteins exhibit dysregulated expression levels in various malignancies and contribute to tumor progression. It has been reported that microproteins interact with many proteins, such as enzymes (e.g., adenosine triphosphate synthase) and signal transducers (e.g., c-Jun), and regulate malignant cell metabolism, proliferation, and metastasis. Moreover, microproteins have been found to play a significant role in multidrug resistance in vitro and in vivo by their activity in DNA repair pathways. Considering that, this review intended to summarize the roles of microproteins in different aspects of tumorigenesis with diagnostic and therapeutic perspectives.

Polyphenols and terpenoids derived from Ocimum species as prospective hepatoprotective drug leads: a comprehensive mechanistic review

Polyphenols and terpenoids derived from Ocimum species as prospective hepatoprotective drug leads: a comprehensive mechanistic review

Hypolipidemic activity of phytochemical combinations: A mechanistic review of preclinical and clinical studies

Hyperlipidemia, a condition characterized by elevated levels of lipids in the blood, poses a significant risk factor for various health disorders, notably cardiovascular diseases. Phytochemical compounds are promising alternatives to the current lipid-lowering drugs, which cause many undesirable effects. Based on in vivo and clinical studies, combining phytochemicals with other phytochemicals, prebiotics, and probiotics and their encapsulation in nanoparticles is more safe and effective for managing hyperlipidemia than monotherapy. To this end, the results obtained and the mechanisms of action of these combinations were examined in detail in this review.

Application of electrostimulation and magnetic stimulation in patients with optic neuropathy: A mechanistic review.

Visual impairment caused by optic neuropathies is irreversible because retinal ganglion cells (RGCs), the specialized neurons of the retina, do not have the capacity for self-renewal and self-repair. Blindness caused by optic nerve neuropathies causes extensive physical, financial, and social consequences in human societies. Recent studies on different animal models and humans have established effective strategies to prevent further RGC degeneration and replace the cells that have deteriorated. In this review, we discuss the application of electrical stimulation (ES) and magnetic field stimulation (MFS) in optic neuropathies, their mechanisms of action, their advantages, and limitations. ES and MFS can be applied effectively in the field of neuroregeneration. Although stem cells are becoming a promising approach for regenerating RGCs, the inhibitory environment of the CNS and the long visual pathway from the optic nerve to the superior colliculus are critical barriers to overcome. Scientific evidence has shown that adjuvant treatments, such as the application of ES and MFS help direct thetransplanted RGCs to extend their axons and form new synapses in the central nervous system (CNS). In addition, these techniques improve CNS neuroplasticity and decrease the inhibitory effects of the CNS. Possible mechanisms mediating the effects of electrical current on biological tissues include the release of anti-inflammatory cytokines, improvement of microcirculation, stimulation of cell metabolism, and modification of stem cell function. ES and MFS have the potential to promote angiogenesis, direct axon growth toward the intended target, and enhance appropriate synaptogenesis in optic nerve regeneration.

Ameliorative properties of quercetin in the treatment of traumatic brain injury: a mechanistic review based on underlying mechanisms.

Traumatic brain injury (TBI) is a leading cause of disability worldwide, with an estimated annual incidence of 27-69million. TBI is a severe condition that can lead to high mortality rates and long-term cognitive, behavioral, and physical impairments in young adults. It is a significant public health concern due to the lack of effective treatments available. Quercetin, a natural flavonoid found in various fruits and vegetables, has demonstrated therapeutic potential with anti-inflammatory, antioxidant, and neuroprotective properties. Recently, some evidence has accentuated the ameliorating effects of quercetin on TBI. This review discusses quercetin's ability to reduce TBI-related damage by regulating many cellular and molecular pathways. Quercetin in vitro and in vivo studies exhibit promise in reducing inflammation, oxidative stress, apoptosis, and enhancing cognitive function post-TBI. Further clinical investigation into quercetin's therapeutic potential as a readily available adjuvant in the treatment of TBI is warranted in light of these findings. This review adds to our knowledge of quercetin's potential in treating TBI by clarifying its mechanisms of action.

Meropenem/Vaborbactam-A Mechanistic Review for Insight into Future Development of Combinational Therapies.

Beta-lactam antibiotics have been a major climacteric in medicine for being the first bactericidal compound available for clinical use. They have continually been prescribed since their development in the 1940s, and their application has saved an immeasurable number of lives. With such immense use, the rise in antibiotic resistance has truncated the clinical efficacy of these compounds. Nevertheless, the synergism of combinational antibiotic therapy has allowed these drugs to burgeon once again. Here, the development of meropenem with vaborbactam-a recently FDA-approved beta-lactam combinational therapy-is reviewed in terms of structure rationale, activity gamut, pharmacodynamic/pharmacokinetic properties, and toxicity to provide insight into the future development of analogous therapies.

Obesity-induced tissue alterations resist weight loss: A mechanistic review.

Interventions aimed at weight control often have limited effectiveness in combating obesity. This review explores how obesity-induced dysfunction in white (WAT) and brown adipose tissue (BAT), skeletal muscle, and the brain blunt weight loss, leading to retention of stored fat. In obesity, increased adrenergic stimulation and inflammation downregulate β-adrenoreceptors and impair catecholaminergic signalling in adipocytes. This disrupts adrenergic-mediated lipolysis, diminishing lipid oxidation in both white and brown adipocytes, lowering thermogenesis and blunting fat loss. Emerging evidence suggests that WAT fibrosis is associated with worse weight loss outcomes; indeed, limiting collagen and laminin-α4 deposition mitigates WAT accumulation, enhances browning, and protects against high-fat-diet-induced obesity. Obesity compromises mitochondrial oxidative capacity and lipid oxidation in skeletal muscle, impairing its ability to switch between glucose and lipid metabolism in response to varying nutrient levels and exercise. This dysfunctional phenotype in muscle is exacerbated in the presence of obesity-associated sarcopenia. Additionally, obesity suppresses sarcolipin-induced sarcoplasmic reticulum calcium ATPase (SERCA) activation, resulting in reduced oxidative capacity, diminished energy expenditure, and increased adiposity. In the hypothalamus, obesity and overnutrition impair insulin and leptin signalling. This blunts central satiety signals, favouring a shift in energy balance toward energy conservation and body fat retention. Moreover, both obese animals and humans demonstrate impaired dopaminergic signalling and diminished responses to nutrient intake in the striatum, which tend to persist after weight loss. This may result in enduring inclinations toward overeating and a sedentary lifestyle. Collectively, the tissue adaptations described pose significant challenges to effectively achieving and sustaining weight loss in obesity.

The footprint of gut microbiota in gallbladder cancer: a mechanistic review.

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system with the worst prognosis. Even after radical surgery, the majority of patients with GBC have difficulty achieving a clinical cure. The risk of tumor recurrence remains more than 65%, and the overall 5-year survival rate is less than 5%. The gut microbiota refers to a variety of microorganisms living in the human intestine, including bacteria, viruses and fungi, which profoundly affect the host state of general health, disease and even cancer. Over the past few decades, substantial evidence has supported that gut microbiota plays a critical role in promoting the progression of GBC. In this review, we summarize the functions, molecular mechanisms and recent advances of the intestinal microbiota in GBC. We focus on the driving role of bacteria in pivotal pathways, such as virulence factors, metabolites derived from intestinal bacteria, chronic inflammatory responses and ecological niche remodeling. Additionally, we emphasize the high level of correlation between viruses and fungi, especially EBV and Candida spp., with GBC. In general, this review not only provides a solid theoretical basis for the close relationship between gut microbiota and GBC but also highlights more potential research directions for further research in the future.

Yoga and Cardiovascular Diseases - A Mechanistic Review.

Yoga is an ancient Indian practice that involves the mind and body. It is a combination of physical exercises and postures with a focus on deep breathing and meditation. Yoga thereby promotes a healthy lifestyle which is one of the key factors in the prevention of various cardiovascular diseases. The practice of yoga might hence be effective in preventing the onset of these diseases. Yoga exerts its beneficial effects by favorable modulation of the autonomic system, reduction in oxidative stress, decreased inflammatory stress, improved endothelial function, and epigenetic changes. These changes might contribute not only to the prevention of cardiovascular diseases but also to delaying and preventing the onset of various modifiable cardiovascular risk factors. This review aims to delineate the possible mechanisms of the effect of yoga on cardiovascular health and its potential beneficial effects.

A mechanistic review on growing multiple therapeutic applications of lutein and its global market research.

Lutein is a naturally occurring carotenoid synthesized by plants and algae that has a beneficial effect on several biological processes and associated ailments. Its immediate application is in ophthalmology, where it significantly lowers the incidences of age-related macular degeneration (AMD). It also has anti-inflammatory action, treatment of diabetic retinopathy, and cataracts, and enhancement of visual contrast. To critically assess lutein biosynthesis, therapeutic applicability, and market research literature. We have discussed its theoretical frameworks, experimental evidence, limitations, as well as clinical trial results, and future research prospects. The literature for this review article was mined and compiled by collecting and analyzing articles from several databases, including ScienceDirect, Google Scholar, PubMed, Wiley Online Library, Patentscope, and ClinicalTrials.gov published until March 30, 2022. Patent publications were identified using the search terms like IC:(C07C67/56) AND EN_AB:(lutein) OR EN_TI:(lutein) OR EN_AB:(extraction) OR EN_TI:(process). According to the literature, lutein is an essential nutrient given that it cannot be synthesized in the human body and acts as an antioxidant, affecting AMD, diabetic retinopathy, Rheumatic diseases, inflammation, and cancer. Due to inadequate production and laborious extraction, lutein is expensive despite its high demand and applicability. Market research predicts a 6.3% compound annual growth rate for lutein by 2032. Optimizing lutein extraction for high yield and purity is necessary. Lutein has proven applicability in various ailments as well as cosmetics that can be developed as a candidate drug for various diseases discussed in the review.

Challenges and opportunities of medicines for treating tendon inflammation and fibrosis: A comprehensive and mechanistic review.

Tendinopathy refers to conditions characterized by collagen degeneration within tendon tissue, accompanied by the proliferation of capillaries and arteries, resulting in reduced mechanical function, pain, and swelling. While inflammation in tendinopathy can play a role in preventing infection, uncontrolled inflammation can hinder tissue regeneration and lead to fibrosis and impaired movement. The inability to regulate inflammation poses a significant limitation in tendinopathy treatment. Therefore, an ideal treatment strategy should involve modulation of the inflammatory process while promoting tissue regeneration. The current review article was prepared by searching PubMed, Scopus, Web of Science, and Google Scholar databases. Several treatment approaches based on biomaterials have been developed. This review examines various treatment methods utilizing small molecules, biological compounds, herbal medicine-inspired approaches, immunotherapy, gene therapy, cell-based therapy, tissue engineering, nanotechnology, and phototherapy. These treatments work through mechanisms of action involving signaling pathways such as transforming growth factor-beta (TGF-β), mitogen-activated protein kinases (MAPKs), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), all of which contribute to the repair of injured tendons.

A mechanistic review of the pharmacological potential of narirutin: a dietary flavonoid.

Flavanones, a type of polyphenol, are found in substantial amounts in citrus fruits. When high- or moderate-dose orange juice consumption occurs, flavanones make up a significant portion of the total polyphenols in plasma. Disaccharide derivative narirutin, mainly dihydroxy flavanone, is found in citrus fruits. The substantial chemotherapeutic potential of narirutin has been amply demonstrated by numerous experimental studies. Consequently, the purpose of this study is to compile the research that has already been done showing narirutin to be a promising anticancer drug, with its mechanism of action being documented in treatment plans for various cancer forms. Narirutin functions in a variety of cancer cells by regulating several pathways that include cell cycle arrest, apoptosis, antiangiogenic, antimetastatic, and DNA repair. Narirutin has been shown to modify many molecular targets linked to the development of cancer, including drug transporters, cell cycle mediators, transcription factors, reactive oxygen species, reactive nitrogen species, and inflammatory cytokines. Taken together, these reviews offer important new information about narirutin's potential as a potent and promising drug candidate for use in medicines, functional foods, dietary supplements, nutraceuticals, and other products targeted at improving the treatment of cancer.

Mechanistic Review on the Role of Gut Microbiota in the Pathology of Cardiovascular Diseases.

Cardiovascular diseases (CVDs), which stand as the primary contributors to illness and death on a global scale, include vital risk factors like hyperlipidemia, hypertension, diabetes, and smoking, to name a few. However, conventional cardiovascular risk factors offer only partial insight into the complexity of CVDs. Lately, a growing body of research has illuminated that the gut microbiome and its by-products are also of paramount importance in the initiation and progression of CVDs. The gastrointestinal tract houses trillions of microorganisms, commonly known as gut microbiota, that metabolize nutrients, yielding substances like trimethylamine-N-oxide (TMAO), bile acids (BAs), short-chain fatty acids (SCFAs), indoxyl sulfate (IS), and so on. Strategies aimed at addressing these microbes and their correlated biological pathways have shown promise in the management and diagnosis of CVDs. This review offers a comprehensive examination of how the gut microbiota contributes to the pathogenesis of CVDs, particularly atherosclerosis, hypertension, heart failure (HF), and atrial fibrillation (AF), explores potential underlying mechanisms, and highlights emerging therapeutic prospects in this dynamic domain.