The Effects of Apigenin in the Treatment of Diabetic Nephropathy: A Systematic Review of Non-clinical Studies.

PURPOSE: Diabetes is one of the important and growing diseases in the world. Among the most common diabetic complications are renal adverse effects. The use of apigenin may prevent the development and progression of diabetes-related injuries. The current study aims to review the effects of apigenin in the treatment of diabetic nephropathy. METHODS: In this review, a systematic search was performed based on PRISMA guidelines for obtaining all relevant studies on "the effects of apigenin against diabetic nephropathy" in various electronic databases up to September 2022. Ninety-one articles were obtained and screened in accordance with the predefined inclusion and exclusion criteria. Seven eligible articles were finally included in this review. RESULTS: The experimental findings revealed that hyperglycemia led to the decreased cell viability of kidney cells and body weight loss and an increased kidney weight of rats; however, apigenin administration had a reverse effect on these evaluated parameters. It was also found that hyperglycemia could induce alterations in the biochemical and renal function-related parameters as well as histopathological injuries in kidney cells or tissue; in contrast, the apigenin administration could ameliorate the hyperglycemia-induced renal adverse effects. CONCLUSION: The results indicated that the use of apigenin could mitigate diabetes-induced renal adverse effects, mainly through its antioxidant, anti-apoptotic, and anti-inflammatory activities. Since the findings of this study are based on experimental studies, suggesting the use of apigenin (as a nephroprotective agent) against diabetic nephropathy requires further clinical studies.

The use of combination therapy for the improvement of colistin activity against bacterial biofilm.

Colistin is used as a last resort for the management of infections caused by multi-drug resistant (MDR) bacteria. However, the use of this antibiotic could lead to different side effects, such as nephrotoxicity, in most patients, and the high prevalence of colistin-resistant strains restricts the use of colistin in the clinical setting. Additionally, colistin could induce resistance through the increased formation of biofilm; biofilm-embedded cells are highly resistant to antibiotics, and as with other antibiotics, colistin is impaired by bacteria in the biofilm community. In this regard, the researchers used combination therapy for the enhancement of colistin activity against bacterial biofilm, especially MDR bacteria. Different antibacterial agents, such as antimicrobial peptides, bacteriophages, natural compounds, antibiotics from different families, N-acetylcysteine, and quorum-sensing inhibitors, showed promising results when combined with colistin. Additionally, the use of different drug platforms could also boost the efficacy of this antibiotic against biofilm. The mentioned colistin-based combination therapy not only could suppress the formation of biofilm but also could destroy the established biofilm. These kinds of treatments also avoided the emergence of colistin-resistant subpopulations, reduced the required dosage of colistin for inhibition of biofilm, and finally enhanced the dosage of this antibiotic at the site of infection. However, the exact interaction of colistin with other antibacterial agents has not been elucidated yet; therefore, further studies are required to identify the precise mechanism underlying the efficient removal of biofilms by colistin-based combination therapy.

Therapeutic Targeting of Krüppel-Like Factor 4 and Its Pharmacological Potential in Parkinson's Disease: a Comprehensive Review.

Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, is found in different human tissues and shows diverse regulatory activities in a cell-dependent manner. In the brain, KLF4 controls various neurophysiological and neuropathological processes, and its contribution to various neurological diseases has been widely reported. Parkinson's disease (PD) is an age-related neurodegenerative disease that might have a connection with KLF4. In this review, we discussed the potential implication of KLF4 in fundamental molecular mechanisms of PD, including aberrant proteostasis, neuroinflammation, apoptosis, oxidative stress, and iron overload. The evidence collected herein sheds new light on KLF4-mediated pathways, which manipulation appears to be a promising therapeutic target for PD management. However, there is a gap in the knowledge on this topic, and extended research is required to understand the translational value of the KLF4-oriented therapeutical approach in PD.

Melatonin in Chemo/Radiation Therapy; Implications for Normal Tissues Sparing and Tumor Suppression: An Updated Review.

Resistance to therapy and the toxicity of normal tissue are the major problems for efficacy associated with chemotherapy and radiotherapy. Drug resistance is responsible for most cases of mortality associated with cancer. Furthermore, their side effects can decrease the quality of life for surviving patients. An enhancement in the tumor response to therapy and alleviation of toxic effects remain unsolved challenges. One of the interesting topics is the administration of agents with low toxicity to protect normal tissues and/or sensitize cancers to chemo/radiotherapy. Melatonin is a natural body hormone that is known as a multitasking molecule. Although it has antioxidant properties, a large number of experiments have uncovered interesting effects of melatonin that can increase the therapeutic efficacy of chemo/radiation therapy. Melatonin can enhance anticancer therapy efficacy through various mechanisms, cells such as the immune system, and modulation of cell cycle and death pathways, tumor suppressor genes, and also through suppression of some drug resistance mediators. However, melatonin may protect normal tissues through the suppression of inflammation, fibrosis, and massive oxidative stress in normal cells and tissues. In this review, we will discuss the distinct effects of melatonin on both tumors and normal tissues. We review how melatonin may enhance radio/chemosensitivity of tumors while protecting normal tissues such as the lung, heart, gastrointestinal system, reproductive system, brain, liver, and kidney.

The role of endoplasmic reticulum stress in promoting aerobic glycolysis in cancer cells: An overview.

Aerobic glycolysis, also known as the Warburg effect, is a metabolic phenomenon frequently observed in cancer cells, characterized by the preferential utilization of glucose through glycolysis, even under normal oxygen conditions. This metabolic shift provides cancer cells with a proliferative advantage and supports their survival and growth. While the Warburg effect has been extensively studied, the underlying mechanisms driving this metabolic adaptation in cancer cells remain incompletely understood. In recent years, emerging evidence has suggested a potential link between endoplasmic reticulum (ER) stress and the promotion of aerobic glycolysis in cancer cells. The ER is a vital organelle involved in protein folding, calcium homeostasis, and lipid synthesis. Various cellular stresses, such as hypoxia, nutrient deprivation, and accumulation of misfolded proteins, can lead to ER stress. In response, cells activate the unfolded protein response (UPR) to restore ER homeostasis. However, prolonged or severe ER stress can activate alternative signaling pathways that modulate cellular metabolism, including the promotion of aerobic glycolysis. This review aims to provide an overview of the current understanding regarding the influence of ER stress on aerobic glycolysis in cancer cells to shed light on the complex interplay between ER stress and metabolic alterations in cancer cells. Understanding the intricate relationship between ER stress and the promotion of aerobic glycolysis in cancer cells may provide valuable insights for developing novel therapeutic strategies targeting metabolic vulnerabilities in cancer.

Peptide-Based Therapeutics in Cancer Therapy.

A monster called cancer is still one of the most challenging human problems and one of the leading causes of death in the world. Different types of treatment methods are used for cancer therapy; however, there are challenges such as high cost and harmful side effects in using these methods. Recent years have witnessed a surge in the development of therapeutic peptides for a wide range of diseases, notably cancer. Peptides are preferred over antibiotics, radiation therapy, and chemotherapy in the treatment of cancer due to a number of aspects, including flexibility, easy modification, low immunogenicity, and inexpensive cost of production. The use of therapeutic peptides in cancer treatment is a novel and intriguing strategy. These peptides provide excellent prospects for targeted drug delivery because of their high selectivity, specificity, small dimensions, good biocompatibility, and simplicity of modification. Target specificity and minimal toxicity are benefits of therapeutic peptides. Additionally, peptides can be used to design antigens or adjuvants for vaccine development. Here, types of therapeutic peptides for cancer therapy will be discussed, such as peptide-based cancer vaccines and tumor-targeting peptides (TTP) and cell-penetrating peptides (CPP).

Revolutionizing treatment for triple-negative breast cancer: Harnessing the power of exosomal miRNAs for targeted therapy.

Triple-negative breast cancer (TNBC) represents a challenging and aggressive form of breast cancer associated with limited treatment options and poor prognosis. Although chemotherapy is a primary therapeutic approach, drug resistance often hinders treatment success. However, the expanding knowledge of TNBC subtypes and molecular biology has paved the way for targeted therapies. Notably, exosomes (extracellular vesicles) have emerged as crucial carriers of tumorigenic factors involved in oncogenesis and drug resistance, facilitating cell-to-cell communication and offering potential as self-delivery systems. Among the cargo carried by exosomes, microRNAs (miRNAs) have gained attention due to their ability to mediate epigenetic changes in recipient cells upon transfer. Research has confirmed dysregulation of exosomal miRNAs in breast cancer cells compared to healthy cells, establishing them as promising biomarkers for cancer diagnosis and prognosis. In this comprehensive review, we summarize the latest research findings that underscore the diagnostic and prognostic significance of exosomal miRNAs in TNBC treatment. Furthermore, we explore contemporary therapeutic approaches utilizing these exosomal miRNAs for the benefit of TNBC patients, shedding light on potential breakthroughs in TNBC management.

WITHDRAWN: Application of Nanoparticles in the Management of Polycystic Ovary Syndrome

The article has been withdrawn at the request of the Corresponding author.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

The effect of conjugated linoleic acids on inflammation, oxidative stress, body composition and physical performance: a comprehensive review of putative molecular mechanisms.

Conjugated linoleic acids (CLAs) are polyunsaturated fatty acids primarily found in dairy products and ruminant animal products such as beef, lamb, and butter. Supplementation of CLAs has recently become popular among athletes due to the variety of health-promoting effects, including improvements in physical performance. Preclinical and some clinical studies have shown that CLAs can reduce inflammation and oxidative stress and favorably modulate body composition and physical performance; however, the results of previously published clinical trials are mixed. Here, we performed a comprehensive review of previously published clinical trials that assessed the role of CLAs in modulating inflammation, oxidative stress, body composition, and select indices of physical performance, emphasizing the molecular mechanisms governing these changes. The findings of our review demonstrate that the effect of supplementation with CLAs on inflammation and oxidative stress is controversial, but this supplement can decrease body fat mass and increase physical performance. Future well-designed randomized clinical trials are warranted to determine the effectiveness of (1) specific doses of CLAs; (2) different dosing durations of CLAs; (3) various CLA isomers, and the exact molecular mechanisms by which CLAs positively influence oxidative stress, inflammation, body composition, and physical performance.

The metformin immunoregulatory actions in tumor suppression and normal tissues protection.

The immune system is the key player in a wide range of responses in normal tissues and tumors to anticancer therapy. Inflammatory and fibrotic responses in normal tissues are the main limitations of chemotherapy, radiotherapy, and also some newer anticancer drugs such as immune checkpoint inhibitors (ICIs). Immune system responses within solid tumors including anti-tumor and tumor-promoting responses can suppress or help tumor growth. Thus, modulation of immune cells and their secretions such as cytokines, growth factors and epigenetic modulators, pro-apoptosis molecules, and some other molecules can be suggested to alleviate side effects in normal tissues and drug-resistance mechanisms in the tumor. Metformin as an anti-diabetes drug has shown intriguing properties such as anti-inflammation, anti-fibrosis, and anticancer effects. Some investigations have uncovered that metformin can ameliorate radiation/chemotherapy toxicity in normal cells and tissues through the modulation of several targets in cells and tissues. These effects of metformin may ameliorate severe inflammatory responses and fibrosis after exposure to ionizing radiation or following treatment with highly toxic chemotherapy drugs. Metformin can suppress the activity of immunosuppressive cells in the tumor through the phosphorylation of AMP-activated protein kinase (AMPK). In addition, metformin may stimulate antigen presentation and maturation of anticancer immune cells, which lead to the induction of anticancer immunity in the tumor. This review aims to explain the detailed mechanisms of normal tissue sparing and tumor suppression during cancer therapy using adjuvant metformin with an emphasis on immune system responses.

The emerging role of microRNA-126 as a potential therapeutic target in cancer: a comprehensive review.

MicroRNA-126 (miR-126) has become a key player in the biology of cancer, playing a variety of functions in carcinogenesis and cancer development. The diagnostic and prognostic potential of miR-126 in diverse cancer types is summarized in this thorough analysis, with an emphasis on its role in tumor angiogenesis, invasion, metastasis, cell proliferation, apoptosis, and treatment resistance. MiR-126 dysregulation is linked to a higher risk of developing cancer and a worse prognosis. Notably, miR-126 affects tumor vascularization and development by targeting vascular endothelial growth factor-A (VEGF-A). Through its impact on genes involved in cell adhesion and migration, it also plays a vital part in cancer cell invasion and metastasis. Additionally, miR-126 controls drug resistance, apoptosis, and cell proliferation, which affects cancer cell survival and treatment response. It may be possible to develop innovative therapeutic approaches to stop tumor angiogenesis, invasion, and metastasis, as well as combat drug resistance by focusing on miR-126 or its downstream effectors. The versatility of miR-126's functions highlights the role that it plays in cancer biology. To understand the processes behind miR-126 dysregulation, pinpoint precise targets, and create efficient therapies, more investigation is required. Utilizing miR-126's therapeutic potential might have a significant influence on cancer treatment plans and patient outcomes.

Small but mighty: How microRNAs drive the deadly progression of cholangiocarcinoma.

Cholangiocarcinoma, also referred to as CCA, is a highly complex epithelial malignancy that can impact various organs and regions of the body, including the perihilar, intrahepatic, and distal organs. This cancer is characterized by the malignant growth of the epithelial lining in the bile ducts, which spans the entire biliary tree and is accountable for disease progression. The current state of affairs concerning CCA is concerning, with poor prognoses, high recurrence rates, and dismal long-term survival rates significantly burden healthcare facilities worldwide. Studies have identified numerous signaling pathways and molecules involved in the development and progression of CCA, including microRNAs, an important class of non-coding RNAs that have the ability to modulate these cellular signaling pathways significantly. In addition, microRNAs may serve as an innovative target for developing novel therapeutic approaches for CCA. In this review, we explore the underlying mechanisms and signaling pathways implicated in the initiation and progression of CCA, focusing on the future direction of utilizing microRNAs as a promising treatment option for this challenging malignancy.

NK cells direct the perspective approaches to cancer immunotherapy.

Natural killer (NK) cells are innate immune cells with cytotoxic potentials to kill cancerous cells in several mechanisms, which could be implied for cancer therapy. While potent, their antitumor activities specially for solid tumors impaired by inadequate tumor infiltration, suppressive tumor microenvironment, cancer-associated stroma cells, and tumor-supportive immune cells. Therefore, manipulating or reprogramming these barriers by prospective strategies might improve current immunotherapies in the clinic or introduce novel NK-based immunotherapies. NK-based immunotherapy could be developed in monotherapy or in combination with other therapeutic regimens such as oncolytic virus therapy and immune checkpoint blockade, as presented in this review.

Angiogenesis and prostate cancer: MicroRNAs comes into view.

Angiogenesis, the formation of new blood vessels, is an important stage in the growth of cancer. Extracellular matrix, endothelial cells, and soluble substances must be carefully coordinated during the multistep procedure of angiogenesis. Inducers and inhibitors have been found to control pretty much every phase. In addition to benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and angiogenesis have a critical role in the initiation and progression of prostate cancer. MicroRNA (miRNA) is endogenous, short, non-coding RNA molecules of almost 22 nucleotides play a role in regulating cellular processes and regulating several genes' expression. Through controlling endothelial migration, differentiation, death, and cell proliferation, miRNAs have a significant function in angiogenesis. A number of pathological and physiological processes, particularly prostate cancer's emergence, depend on the regulation of angiogenesis. Investigating the functions played with miRNAs in angiogenesis is crucial because it might result in the creation of novel prostate cancer therapies that entail regulating angiogenesis. The function of several miRNAs and its targeting genes engaged in cancer of the prostate angiogenesis will be reviewed in this review in light of the most recent developments. The potential clinical utility of miRNAs potentially a novel therapeutic targets will also be explored, as well as their capacity to control prostate cancer angiogenesis and the underlying mechanisms.

The role of protein kinases in diabetic neuropathic pain: an update review.

Objectives: Diabetic neuropathic pain (DNP) is a debilitating symptom of diabetic neuropathy which seriously impairs patient's quality of life. Currently, there is no specific therapy for DNP except for duloxetine and gabapentin that show limited utility in alleviating DNP. The present review aims to discuss the central role of protein kinases in the pathogenesis of DNP and their therapeutic modulation. Methods: Scopus, PubMed, and Google scholar were searched up to January 2022 to find relevant studies with English language in which the roles of proteins kinases in DNP were examined. Results: DNP is associated with hyperactivity in pain sensory neurons and therapies aim to specifically suppress redundant discharges in these neurons without affecting the activity of other sensory and motor neurons. Transient receptor potential vanilloid 1 (TRPV1) and purinergic 2 × 7 receptors (P2 × 7R) are two receptor channels, highly expressed in pain sensory neurons and their blockade produces remarkable analgesic effects in DNP. The activities of receptor channels are mainly regulated by the protein kinases whose modulation provides remarkable analgesic effects in DNP models. Conclusion: Capsaicin, TRPV1 modulator, is the only agent successfully examined in clinical trials with promising effects in patients with DNP. Current data suggest that blocking calcium calmodulin dependent protein kinase II (CaMKII) is superior to other approaches, considering its pivotal role in regulating the pain neuron potentials. By this means, DNP alleviation is achievable without affecting the activity of other sensory or motor neurons.

Cancer Stem Cells in Colorectal Cancer: Implications for Targeted Immunotherapies.

PURPOSE: Colorectal cancers are composed of heterogeneous cell populations in the concepts of genetic and functional degrees that among them cancer stem cells are identified with their self-renewal and stemness capability mediating primary tumorigenesis, metastasize, therapeutic resistance, and tumor recurrence. Therefore, understanding the key mechanisms of stemness in colorectal cancer stem cells (CRCSCs) provides opportunities to discover new treatments or improve existing therapeutic regimens. METHODS: We review the biological significance of stemness and the results of potential CRCSC-based targeted immunotherapies. Then, we pointed out the barriers to targeting CRCSCs in vivo and highlight new strategies based on synthetic and biogenic nanocarriers for the development of future anti-CRCSC trials. RESULTS: The CSCs' surface markers, antigens, neoantigens, and signaling pathways supportive CRCSCs or immune cells that are interacted with CRCSCs could be targeted by immune monotherapy or in formulation with developed nanocarriers to overcome the resistant mechanisms in immune evader CRCSCs. CONCLUSION: Identification molecular and cellular cues supporting stemness in CRCSCs and their targeting by nanoimmunotherpy can improve the efficacy of existed therapies or explore novel therapeutic options in future.

Advanced injectable hydrogels for bone tissue regeneration.

Diseases or defects of the skeleton are hazardous because of their specificity and intricacy. Bone tissue engineering has become an important area of research that offers promising new tools for making biomimetic hydrogels that can be used to treat bone diseases. New hydrogels with a distinctive 3D network structure, high water content, and functional capabilities are ranked among the most promising candidates for bone tissue engineering. This makes them helpful in treating cartilage injury, skull deformity, and arthritis. This review will briefly introduce the variety of biocompatible functional hydrogels used in cell culture and bone tissue regeneration. Many gel design concepts, such as crosslinking procedures, controlled release properties, and alternative bionic methodology, were stressed regarding injectable hydrogels to form bone tissue. Hydrogels manufactured from biocompatible materials are a promising option for minimally invasive surgery because of their adaptable physicochemical qualities, ability to fill irregularly shaped defect sites, and ability to grow hormones or release drugs in response to external stimuli. Also included in this overview is a quick rundown of the more practical designs employed in treating bone disorders. Essential details on injectable hydrogel scaffolds for bone tissue regeneration are described in this article.