Effects of metformin on cancers in experimental and clinical studies: Focusing on autophagy and AMPK/mTOR signaling pathways.

Metformin (MET) is a preferred drug for the treatment of type 2 diabetes mellitus. Recent studies show that apart from its blood glucose-lowering effects, it also inhibits the development of various tumours, by inducing autophagy. Various studies have confirmed the inhibitory effects of MET on cancer cell lines' propagation, migration, and invasion. The objective of the study was to comprehensively review the potential of MET as an anticancer agent, particularly focusing on its ability to induce autophagy and inhibit the development and progression of various tumors. The study aimed to explore the inhibitory effects of MET on cancer cell proliferation, migration, and invasion, and its impact on key signaling pathways such as adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and PI3K. This review noted that MET exerts its anticancer effects by regulating key signalling pathways such as phosphoinositide 3-kinase (PI3K), LC3-I and LC3-II, Beclin-1, p53, and the autophagy-related gene (ATG), inhibiting the mTOR protein, downregulating the expression of p62/SQSTM1, and blockage of the cell cycle at the G0/G1. Moreover, MET can stimulate autophagy through pathways associated with the 5' AMPK, thereby inhibiting he development and progression of various human cancers, including hepatocellular carcinoma, prostate cancer, pancreatic cancer, osteosarcoma, myeloma, and non-small cell lung cancer. In summary, this detailed review provides a framework for further investigations that may appraise the autophagy-induced anticancer potential of MET and its repurposing for cancer treatment.

Challenges and opportunities for cancer stem cell-targeted immunotherapies include immune checkpoint inhibitor, cancer stem cell-dendritic cell vaccine, chimeric antigen receptor immune cells, and modified exosomes.

Cancer stem cells (CSCs) are associated with the tumor microenvironment (TME). CSCs induce tumorigenesis, tumor recurrence and progression, and resistance to standard therapies. Indeed, CSCs pose an increasing challenge to current cancer therapy due to their stemness or self-renewal properties. The molecular and cellular interactions between heterogeneous CSCs and surrounding TME components and tumor-supporting immune cells show synergistic effects toward treatment failure. In the immunosuppressive TME, CSCs express various immunoregulatory proteins, growth factors, metabolites and cytokines, and also produce exosomes, a type of extracellular vesicles, to protect themselves from host immune surveillance. Among these, the identification and application of CSC-derived exosomes could be considered for the development of therapeutic approaches to eliminate CSCs or cancer, in addition to targeting the modulators that remodel the composition of the TME, as reviewed in this study. Here, we introduce the role of CSCs and how their interaction with TME complicates immunotherapies, and then present the CSC-based immunotherapy and the limitation of these therapies. We describe the biology and role of tumor/CSC-derived exosomes that induce immune suppression in the TME, and finally, introduce their potentials for the development of CSC-based targeted immunotherapy in the future.

CRISPR/Cas-based colorimetric biosensors: a promising tool for the diagnosis of bacterial foodborne pathogens in food products.

Some physical phenomena and various chemical substances newly introduced in nanotechnology have allowed scientists to develop valuable devices in the field of food sciences. Regarding such progress, the identification of foodborne pathogenic microorganisms is an imperative subject nowadays. These bacterial species have been found to cause severe health impacts after food ingestion and can result in high mortality in acute cases. The rapid detection of foodborne bacterial species at low concentrations is in high demand in recent diagnostics. CRISPR/Cas-mediated biosensors possess the potential to overcome several challenges in classical assays such as complex pretreatments, long turnaround time, and insensitivity. Among them, colorimetric nanoprobes based on the CRISPR strategy afford promising devices for POCT (point-of-care testing) since they can be visualized with the naked eye and do not require diagnostic apparatus. In this study, we briefly classify and discuss the working principles of the different CRISPR/Cas protein agents that have been employed in biosensors so far. We assess the current status of the CRISPR system, specifically focusing on colorimetric biosensing platforms. We discuss the utilization of each Cas effector in the detection of foodborne pathogens and examine the restrictions of the existing technology. The challenges and future opportunities are also indicated and addressed.

Critical roles of long noncoding RNA H19 in cancer.

Long noncoding RNAs (lncRNAs) are a category of noncoding RNAs characterized by their length, often exceeding 200 nucleotides. There is a growing body of data that indicate the significant involvement of lncRNAs in a wide range of disorders, including cancer. lncRNA H19 was among the initial lncRNAs to be identified and is transcribed from the H19 gene. The H19 lncRNA exhibits significant upregulation in a diverse range of human malignancies, such as breast, colorectal, pancreatic, glioma, and gastric cancer. Moreover, the overexpression of H19 is frequently associated with a worse prognosis among individuals diagnosed with cancer. H19 has been shown to have a role in facilitating several cellular processes, including cell proliferation, invasion, migration, epithelial-mesenchymal transition, metastasis, and apoptosis. This article summarizes the aberrant upregulation of H19 in human malignancies, indicating promising avenues for future investigations on cancer diagnostics and therapeutic interventions.

The interaction between lncRNAs and transcription factors regulating autophagy in human cancers: A comprehensive and therapeutical survey.

Autophagy, as a highly conserved cellular process, participates in cellular homeostasis by degradation and recycling of damaged organelles and proteins. Besides, autophagy has been evidenced to play a dual role through cancer initiation and progression. In the early stage, it may have a tumor-suppressive function through inducing apoptosis and removing damaged cells and organelles. However, late stages promote tumor progression by maintaining stemness features and induction of chemoresistance. Therefore, identifying and targeting molecular mechanisms involved in autophagy is a potential therapeutic strategy for human cancers. Multiple transcription factors (TFs) are involved in the regulation of autophagy by modulating the expression of autophagy-related genes (ATGs). In addition, a wide array of long noncoding RNAs (lncRNAs), a group of regulatory ncRNAs, have been evidenced to regulate the function of these autophagy-related TFs through tumorigenesis. Subsequently, the lncRNAs/TFs/ATGs axis shows great potential as a therapeutic target for human cancers. Therefore, this review aimed to summarize new findings about the role of lncRNAs in regulating autophagy-related TFs with therapeutic perspectives.

Choline chloride/urea as a green and efficient deep eutectic solvent in three-component and four-component synthesis of novel pyrazole and pyrano[2,3-c] pyrazole derivatives with antibacterial and antifungal activity.

In this study, choline chloride/urea was used as a green deep eutectic solvent in the three-component reaction of hydrazine/phenylhydrazine, malononitrile, and aromatic aldehydes for synthesizing pyrazole derivatives, and in the four-component reaction of methyl/ethyl acetoacetate, hydrazine/phenylhydrazine, malononitrile, and aromatic aldehydes for synthesizing pyrano[2,3-c]pyrazole derivatives. Elemental analysis, 1H, and 13C NMR spectroscopy were used to confirm the structure of the synthesized pyrazole and pyrano[2,3-c] pyrazole derivatives. The antimicrobial effects of the synthesized pyrazole and pyrano[2,3-c] pyrazole derivatives were investigated. In antimicrobial tests, instructions from clinical and laboratory standards institutes were used. Antimicrobial study was done on pathogenic gram-positive and gram-negative species, and specialized aquatic strains and fungal species. Using choline chloride/urea, novel pyrazole derivatives and pyrano[2,3-c]pyrazole derivatives were synthesized, and other derivatives were synthesized with higher efficiency in less time than some previously reported methods. MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) obtained for derivatives were higher than some antibiotic drugs. Synthesis and reports of new derivatives of pyrazole and pyrano[2,3-c]pyrazole, and investigation and reports of their antimicrobial properties on gram-positive, gram-negative, and specialized aquatic and fungal species are among the novel and important findings of this study.

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.

Six-Year Study on Cutaneous Leishmaniasis in Al-Muthanna, Iraq: Molecular Identification Using ITS1 Gene Sequencing.

BACKGROUND: The current study aimed to determine the prevalence of cutaneous leishmaniasis (CL) in Al-Muthanna province (Iraq) and to characterize the Leishmania species that cause cutaneous lesions through conventional polymerase chain reaction techniques in some patients during the first 7 months of the year 2020. MATERIALS AND METHODS: Medical information on patients with CL was obtained from archived records at the Al-Muthanna Health Office's Public Health Department (2015-2020). In the Al-Hussein Teaching Hospital laboratory, 95 CL samples were collected and examined microscopically for molecular characterization using Giemsa staining. RESULTS: Between 2015 and 2020, 2,325 patients (1,184 men and 1,141 women) were enrolled. Although CL occurred across all age groups, those aged range of 5-14 years had the highest proportion of infections (53.0%). This study found that most infections occurred between December and February, peaking in January. Only 63 of 95 CL samples were positive for the Internal Transcribed Spacer 1 region. L. tropica was found in 39 samples (61.9%), whereas L. major was found in 24 samples (38.1%), in CL patients. Although dermal lesions develop in all body regions, a single lesion is the most common. The upper limbs (13 of 16 samples, 33.3%)were infected with L. tropica, whereas the lower limbs (9 of 14 samples, 37.5%) were infected with L. major. In contrast to L. major, most L. tropica lesions occur in urban areas. CONCLUSION: Our study indicates that CL is endemic in the Al-Muthanna province and that two Leishmania spp. coexist in the province. Molecular diagnosis is a vital component in determining many clinical symptoms of the Leishmania parasite as well as implementing suitable therapeutic, epidemiological, and control strategies.

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.

Neuroprotective effects of gemfibrozil in neurological disorders: Focus on inflammation and molecular mechanisms.

BACKGROUND: Gemfibrozil (Gem) is a drug that has been shown to activate PPAR-α, a nuclear receptor that plays a key role in regulating lipid metabolism. Gem is used to lower the levels of triglycerides and reduce the risk of coronary heart disease in patients. Experimental studies in vitro and in vivo have shown that Gem can prevent or slow the progression of neurological disorders (NDs), including cerebral ischemia (CI), Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Neuroinflammation is known to play a significant role in these disorders. METHOD: The literature review for this study was conducted by searching Scopus, Science Direct, PubMed, and Google Scholar databases. RESULT: The results of this study show that Gem has neuroprotective effects through several cellular and molecular mechanisms such as: (1) Gem has the ability to upregulate pro-survival factors (PGC-1α and TFAM), promoting the survival and function of mitochondria in the brain, (2) Gem strongly inhibits the activation of NF-κB, AP-1, and C/EBPß in cytokine-stimulated astroglial cells, which are known to increase the expression of iNOS and the production of NO in response to proinflammatory cytokines, (3) Gem protects dopamine neurons in the MPTP mouse model of PD by increasing the expression of PPARα, which in turn stimulates the production of GDNF in astrocytes, (4) Gem reduces amyloid plaque pathology, reduces the activity of glial cells, and improves memory, (5) Gem increases myelin genes expression (MBP and CNPase) via PPAR-ß, and (6) Gem increases hippocampal BDNF to counteract depression. CONCLUSION: According to the study, Gem was investigated for its potential therapeutic effect in NDs. Further research is needed to fully understand the therapeutic potential of Gem in NDs.

Detailed role of microRNA-mediated regulation of PI3K/AKT axis in human tumors.

The regulation of signal transmission and biological processes, such as cell proliferation, apoptosis, metabolism, migration, and angiogenesis are greatly influenced by the PI3K/AKT signaling pathway. Highly conserved endogenous non-protein-coding RNAs known as microRNAs (miRNAs) have the ability to regulate gene expression by inhibiting mRNA translation or mRNA degradation. MiRNAs serve key role in PI3K/AKT pathway as upstream or downstream target, and aberrant activation of this pathway contributes to the development of cancers. A growing body of research shows that miRNAs can control the PI3K/AKT pathway to control the biological processes within cells. The expression of genes linked to cancers can be controlled by the miRNA/PI3K/AKT axis, which in turn controls the development of cancer. There is also a strong correlation between the expression of miRNAs linked to the PI3K/AKT pathway and numerous clinical traits. Moreover, PI3K/AKT pathway-associated miRNAs are potential biomarkers for cancer diagnosis, therapy, and prognostic evaluation. The role and clinical applications of the PI3K/AKT pathway and miRNA/PI3K/AKT axis in the emergence of cancers are reviewed in this article.

A thorough and current study of miR-214-related targets in cancer.

Cancer is a complex genetic anomaly involving coding and non-coding transcript structural and expressive irregularities. A class of tiny non-coding RNAs known as microRNAs (miRNAs) regulates gene expression at the post-transcriptional level by binding only to messenger RNAs (mRNAs). Due to their capacity to target numerous genes, miRNAs have the potential to play a significant role in the development of tumors by controlling several biological processes, including angiogenesis, drug resistance, metastasis, apoptosis, proliferation, and drug resistance. According to several recent studies, miRNA-214 has been linked to the emergence and spread of tumors. The human genome's q24.3 arm contains the DNM3 gene, which is about 6 kb away and includes the microRNA-214. Its primary purpose was the induction of apoptosis in cancerous cells. The multifaceted and complex functions of miR-214 as a modulator in neoplastic conditions have been outlined in the current review.

Advances in preparation, biomedical, and pharmaceutical applications of chitosan-based gold, silver, and magnetic nanoparticles: A review.

During the last decades, the ever-increasing incidence of various diseases, like cancer, has led to a high rate of death worldwide. On the other hand, conventional modalities (such as chemotherapy and radiotherapy) have not indicated enough efficiency in the diagnosis and treatment of diseases. Thus, potential novel approaches should be taken into consideration to pave the way for the suppression of diseases. Among novel approaches, biomaterials, like chitosan nanoparticles (CS NPs, N-acetyl-glucosamine and D-glucosamine), have been approved by the FDA for some efficient pharmaceutical applications. These NPs owing to their physicochemical properties, modification with different molecules, biocompatibility, serum stability, less immune response, suitable pharmacokinetics and pharmacodynamics, etc. have received deep attention among researchers and clinicians. More importantly, the impact of CS polysaccharide in the synthesis, preparation, and delivery of metallic NPs (like gold, silver, and magnetic NPs), and combination of CS with these metallic NPs can further facilitate the diagnosis and treatment of diseases. Metallic NPs possess some features, like converting NIR photon energy into thermal energy and anti-microorganism capability, and can be a potential candidate for the diagnosis and treatment of diseases in combination with CS NPs. These combined NPs would be efficient pharmaceuticals in the future.

NLRP3 inflammasome pathway in atherosclerosis: Focusing on the therapeutic potential of non-coding RNAs.

NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome pathway has a critical role in the pathogenesis of atherosclerosis. Activation of this pathway is implicated in the subendothelial inflammation and atherosclerosis progression. The NLRP3 inflammasome are cytoplasmic sensors with the distinct capacity to identify a wide range of inflammation-related signals, which enhance NLRP3 inflammasome assembly and allow it to trigger inflammation. This pathway is triggered by a variety of intrinsic signals which exist in atherosclerotic plaques, like cholesterol crystals and oxidized LDL. Further pharmacological findings indicated that NLRP3 inflammasome enhanced caspase-1-mediated secretion of pro-inflammatory mediators like interleukin (IL)- 1ß/18. Newly published cutting-edge studies suggested that non-coding RNAs (ncRNAs) including microRNAs (miRNAs, miRs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) are major modulators of NLRP3 inflammasome in atherosclerosis. Therefore, in this review, we aimed to discuss the NLRP3 inflammasome pathway, biogenesis of ncRNAs as well as the modulatory role of ncRNAs in regulating the various mediators of NLRP3 inflammasome pathway including TLR4, NF-kB, NLRP3, and caspase 1. We also discussed the importance of NLRP3 inflammasome pathway-related ncRNAs as a diagnostic biomarker in atherosclerosis and current therapeutics in the modulation of NLRP3 inflammasome in atherosclerosis. Finally, we speak about the limitations and future prospects of ncRNAs in regulating inflammatory atherosclerosis via the NLRP3 inflammasome pathway.

The effects of Chlorella vulgaris on cardiovascular risk factors: A comprehensive review on putative molecular mechanisms.

High incidence rate of cardiovascular disease (CVD) make this condition as an important public health concern. The use of natural products in treating this chronic condition has increased in recent years one of which is the single-celled green alga Chlorella. Chlorella vulgaris (CV) has been studied for its potential benefits to human health due to its biological and pharmacological features. CV contains a variety of macro and micronutrients, including proteins, omega-3, polysaccharides, vitamins, and minerals. Some studies have indicated that taking CV as a dietary supplement can help reduce inflammation and oxidative stress. In some studies, cardiovascular risk factors that are based on hematological indices did not show these benefits, and no molecular mechanisms have been identified. This comprehensive review summarized the research on the cardio-protective benefits of chlorella supplementation and the underlying molecular processes.