BACKGROUND: Lung adenocarcinoma (LUAD) is a major type of lung cancer worldwide, and under the pandemic coronavirus disease 2019 (COVID-19), its cancer burden is enlarged. This study aimed to explore potential drug targets and potential drugs for developing effective treatments for patients with both lung cancer and COVID-19. METHOD: The interaction network of molecule compounds-target genes was constructed based on Traditional Chinese Medicines (TCMs) and gene expression data from public databases. The potential effectiveness of drugs was analyzed by molecular docking and molecular dynamics simulation. Western blot, transfection assay, Immunohistochemistry (IHC) staining, and flow cytometry were performed to investigate the function of HSP90AA1 in LUAD cells. RESULT: Eight target genes (GSK3B, HMOX1, HSP90AA1, ICAM1, MAPK1, PLAU, RELA and TNFSF15.) were identified, and two of them (HSP90AA1 and RELA) were significantly associated with LUAD prognosis. Luteolin was discovered to bind with HSP90AA1. Moreover, In vitro cell experiments demonstrated that HSP90AA1 had higher expression in A549 cells, promoted cell viability and suppressed apoptosis in A549 cells and H1299 cells. CONCLUSION: HSP90AA1 was a target gene for further designing effective drugs for LUAD patients. Luteolin was a potential drug for treating patients with both LUAD and COVID-19.

Turmerones are major bioactive compounds of Curcuma species with several beneficial pharmacological activities. In addition, various in vivo and in vitro studies noted that turmerones could affect different cytokines, metabolic pathways, and targets. Turmerones will have the potential to be a candidate agent to lessen many pathological and immunological conditions as a result of these pharmacological activities. In this review, we provided information about the pharmacological actions of turmerones using search engines such as PubMed, Google Scholar, Scopus, and Web of Science.

In recent decades, the world has gained experience of the dangerous effects of pandemic events caused by emerging respiratory viruses. In particular, annual epidemics of influenza are responsible for severe illness and deaths. Even if conventional influenza vaccines represent the most effective tool for preventing virus infections, they are not completely effective in patients with severe chronic disease and immunocompromised and new small molecules have emerged to prevent and control the influenza viruses. Thus, the attention of chemists is continuously focused on the synthesis of new antiviral drugs able to interact with the different molecular targets involved in the virus replication cycle. To date, different classes of influenza viruses inhibitors able to target neuraminidase enzyme, hemagglutinin protein, Matrix-2 (M2) protein ion channel, nucleoprotein or RNA-dependent RNA polymerase have been synthesized using several synthetic strategies comprising the chemical modification of currently used drugs. The best results, in terms of inhibitory activity, are in the nanomolar range and have been obtained from the chemical modification of clinically used drugs such as Peramivir, Zanamivir, Oseltamir, Rimantadine, as well as sialylated molecules, and hydroxypyridinone derivatives. The aim of this review is to report, covering the period 2016-2022, the most recent routes related to the synthesis of effective influenza virus inhibitors.

BACKGROUND: RNA methylation modification is not only intimately interrelated with cancer development and progression but also actively influences immune cell infiltration in the tumor microenvironment (TME). RNA methylation modification genes influence the therapeutic progression of lung adenocarcinoma (LUAD), and mining RNA methylation modification prognosis-related markers in LUAD is crucial for its precise prognosis. METHODS: RNA-Seq data and Gene sets were collected from online databases or published literature. Genomic variation analysis was conducted by the Maftools package. RNA methylation-immune-related lncRNAs were obtained by Pearson correlation analysis. Then, Consistent clustering analysis was performed to obtain RNA methylation modification-immune molecular subtypes (RMM-I Molecular subtypes) in LUAD based on selected lncRNAs. COX and random survival forest analysis were carried out to construct the RMM-I Score. The receiver operating characteristic (ROC) curve and Kaplan Meier survival analysis were used to assess survival differences. Tumor immune microenvironment was assessed through related gene signatures and CIBERSORT algorithm. In addition, drug sensitivity analysis was executed by the pRRophetic package. RESULTS: Four RNA methylation modified-immune molecular subtypes (RMM-I1, RMM-I2, RMM-I3, RMM-I4) were presented in LUAD. Patients in RMM-I4 exhibited excellent survival advantages and immune activity. HAVCR2, CD274, and CTLA-4 expression were activated in RMM-I4, which might be heat tumors and a potential beneficial group for immunotherapy. OGFRP1, LINC01116, DLGAP1-AS2, CRNDE, LINC01137, MIR210HG, and CYP1B1-AS1 comprised the RMM-I Score. The RMM-I Score exhibited excellent accuracy in the prognostic assessment of LUAD, as patients with a low RMM-I Score exhibited remarkable survival advantage. Patients with a low RMM-I score might be more sensitive to treatment with Docetaxel, Vinorelbine, Paclitaxel, Cisplatin, and immunotherapy. CONCLUSION: The RMM-I molecular subtype constituted the novel molecular characteristic subtype of LUAD, which complemented the existing pathological typing. More refined and accurate molecular subtypes provide help to reveal the mechanism of LUAD development. In addition, the RMM-I score offers a reliable tool for accurate prognosis of LUAD.

The engineering of nanoscale materials has broadened the scope of nanotechnology in a restricted functional system. Today, significant priority is given to immediate health diagnosis and monitoring tools for point-of-care testing and patient care. Graphene, as a one-atom carbon compound, has the potential to detect cancer biomarkers and its derivatives. The atom-wide graphene layer specialises in physicochemical characteristics, such as improved electrical and thermal conductivity, optical transparency, and increased chemical and mechanical strength, thus making it the best material for cancer biomarker detection. The outstanding mechanical, electrical, electrochemical, and optical properties of two-dimensional graphene can fulfil the scientific goal of any biosensor development, which is to develop a more compact and portable point-of-care device for quick and early cancer diagnosis. The bio-functionalisation of recognised biomarkers can be improved by oxygenated graphene layers and their composites. The significance of graphene that gleans its missing data for its high expertise to be evaluated, including the variety in surface modification and analytical reports. This review provides critical insights into graphene to inspire research that would address the current and remaining hurdles in cancer diagnosis.

Breast carcinoma is among the most frequent cancerous tumour in females around the globe. The major modalities now employed in the therapeutic management of breast cancer include surgeries, chemotherapy, and specialized medicines. Despite their potential to help individuals' problems, they are also associated with many negative impacts. As a result, natural products are increasingly regarded to be a preferable alternative. Alkaloids are essential biochemical substances that can be used to develop new drugs. Numerous alkaloids that originate from natural plants have been shown in vitro and in vivo to have anti-proliferation and anti-metastasis actions on different kinds of carcinoma. According to the data collected in this study, the utilization of alkaloids as anti-tumor medicines appears to be extremely potent; nevertheless, extensive studies and clinical trials are required before utilizing individual alkaloids. In this overview, we provide a detailed and vital exploration of pre-existing alkaloids possessing anti-tumor activities due to bioactive compounds. This study also includes an overview of synthesized analogues and pharmacological characteristics that will be beneficial to scientists working on alkaloids for medicinal purposes. In a recent survey of the literature, alkaloids are an important component of plant-derived antitumor medicines that hold great potential for the future development of cancer therapy and preventive therapies. We have also discussed structural analysis relationship (SAR) studies. Moreover, it covers clinical trial medications and FDA-approved medicines from the last five years that will be useful in further research.

Methylene blue (MB) has been routinely used to treat methemoglobinemia. In the body, MB is reduced to leucomethylene blue (LMB) by NADPH-dependent methemoglobin (MetHB) reductase, and then LMB reduces Fe3+ to Fe2+. In glucose-6-phosphate dehydrogenase (G6PD) deficiency, NADPH is not produced sufficiently to protect erythrocytes against oxidative stress and to take part in relevant biochemical reactions. Since MB is an oxidative agent, its administration in individuals with G6PD deficiency leads to an increased risk of hemolysis through oxidative stress and even death. Therefore, its administration has been prohibited from treating methemoglobinemia in G6PD patients. As an antioxidant and direct reducing agent for Fe3+, LMB may be prescribed for treating MetHB in patients with G6PD deficiency. Considering the biochemical process of turning MB into LBM and the reducing nature of LMB, it seems LMB is a safer drug than MB in treating methemoglobinemia. LMB can even be administrated in other treatments without any concern about increasing oxidative stress, exacerbating the inflammation. Proof-of-concept experimental and clinical trials could substantiate this hypothesis.

INTRODUCTION: Circulating microRNAs (miRNAs) serve as noninvasive diagnostic markers in many cancers. This meta-analysis aims to evaluate the diagnostic efficacy of circulating microRNAs for melanoma. MATERIAL AND METHODS: The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and ROC curve were evaluated using the Meta-Disc V.1.4 and Comprehensive Meta-Analysis V.3.3 software packages. To investigate the heterogeneity, the I2 and Chi-square tests were used. The publishing bias was evaluated using Begg's rank correlation and Egger regression asymmetry tests. RESULTS: A total of 9 articles covering 13 studies (more than 50 miRs individually and in combination) were included, containing 1,355 participants (878 cases and 477 controls). The overall pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and AUC were 0.78 (95% CI: 0.76-0.81), 0.80 (95% CI: 0.77-0.83), 4.32 (95% CI: 3.21-5.82), 0.17 (95% CI: 0.09-0.32), 28.0 (95% CI: 15.34-51.09), and 0.91, respectively. According to Begg's and Egger's tests, there was no publication bias (Begg's p = 0.160 and Egger's p = 0.289). CONCLUSION: Circulating miRNAs can serve as fair and non-invasive diagnostic biomarkers for melanoma. Additionally, specific miRNAs still need to be discovered for diagnosing melanoma.

Identifying metabolic signatures induced by the immune response to vaccines allows to discriminate vaccinated from non-vaccinated subjects and decipher the molecular mechanisms associated with the host immune response. This review illustrates and discusses the results of metabolomics-based studies on the innate and adaptive immune response to vaccines, long-term functional reprogramming (immune memory), and adverse reactions. Glycolysis is not overexpressed by vaccines, suggesting that the immune cell response to vaccinations does not require rapid energy availability as that is necessary during an infection. Vaccines strongly impact lipids metabolism, including saturated or unsaturated fatty acids, inositol phosphate, and cholesterol. Cholesterol is strategic for synthesizing 25-hydroxycholesterol in activated macrophages and dendritic cells and stimulates the conversion of macrophages and T cells in M2 macrophage and Treg, respectively. In conclusion, the large-scale application of metabolomics enables the identification of candidate predictive biomarkers of vaccine efficacy/tolerability.

This review focuses on recent trends in the binding study of various antimalarial agents with serum albumins in detail. Serum albumin has a significant role in the transport of drugs and endogenous ligands. The nature and magnitude of serum albumin and drug interactions have a tremendous impact on the pharmacological behavior and toxicity of that drug. Binding of drug to serum albumin not only controls its free and active concentration, but also provides a reservoir for a long duration of action. This ultimately affects drug absorption, distribution, metabolism, and excretion. Such interaction determines the actual drug efficacy as the drug action can be correlated with the amount of unbound drug. With the advancement in spectroscopic techniques and simulation studies, binding studies play an increasingly important role in biophysical and biomedical science, especially in the field of drug delivery and development. This review assesses the insight we have gained so far to improve drug delivery and discovery of antimalarials on the basis of a plethora of drug-serum protein interaction studies done so far.

PURPOSE: Ototoxicity is one of the major adverse effects of cisplatin therapy which restrict its clinical application. Alpha-lipoic acid administration may mitigate cisplatin-induced ototoxicity. In the present study, we reviewed the protective potentials of alpha-lipoic acid against the cisplatin-mediated ototoxic adverse effects. METHODS: Based on the PRISMA guideline, we performed a systematic search for the identification of all relevant studies in various electronic databases up to June 2022. According to the inclusion and exclusion criteria, the obtained articles (n=59) were screened and 13 eligible articles were finally included in the present study. RESULTS: The findings of in-vitro experiments showed that cisplatin treatment significantly reduced the auditory cell viability in comparison with the control group; nevertheless, the alpha-lipoic acid co-administration protected the cells against the reduction of cell viability induced by cisplatin treatment. Moreover, the in-vivo results of the auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) tests revealed a decrease in DPOAE and an increase in ABR threshold of cisplatin-injected animals; however, it was shown that alpha-lipoic acid co-treatment had an opposite pattern on the evaluated parameters. Other findings demonstrated that cisplatin treatment could significantly induce the biochemical and histopathological alterations in inner ear cells/tissue; in contrast, alpha-lipoic acid co-treatment ameliorated the cisplatin-mediated biochemical and histological changes. CONCLUSION: The findings of audiometry, biochemical parameters, and histological evaluation showed that alpha-lipoic acid co-administration alleviates the cisplatin-induced ototoxicity. The protective role of alpha-lipoic acid against the cisplatin-induced ototoxicity can be due to different mechanisms of anti-oxidant, anti-apoptotic, anti-inflammatory activities, and regulation of cell cycle progression.

Statins are HMG-CoA reductase inhibitors and decrease plasma low-density lipoprotein cholesterol (LDL-C) levels. They are well tolerated, and because of their LDL-C-lowering effect, they are utilized to decrease the risk of atherosclerosis and cardiovascular disease. However, statins have pleiotropic effects, including immunomodulatory, anti-inflammatory, antioxidant, and anticancer. Currently, oral administration is the only Food and Drug Administration (FDA)-approved route of administration for statins. However, other administration routes have demonstrated promising results in different pre-clinical and clinical studies. For instance, statins also seem beneficial in dermatitis, psoriasis, vitiligo, hirsutism, uremic pruritus, and graft-versus-host disease. Topically applied statins have been studied to treat seborrhea, acne, rhinophyma, and rosacea. They also have beneficial effects in contact dermatitis and wound healing in animal studies, (HIV) infection, osseointegration, porokeratosis, and some ophthalmologic diseases. Topical and transdermal application of statins is a non-invasive drug administration method that has shown significant results in bypassing the first-pass metabolism in the liver, thereby reducing possible adverse effects. This study reviews the multifaceted molecular and cellular impacts of statins, their topical and transdermal application, novel delivery systems, such as nanosystems for topical and transdermal administration and the challenges concerning this approach.

Since the discovery of cephalostatins, which have shown remarkable activity against human cancer cells, they have attracted the attention of researchers to target the synthesis of such impressive, complicated molecules using the green desymmetrization approach. In the current review, we report the progress in the desymmetrization of symmetrical bis-steroidal pyrazines (BSPs) as an approach toward potentially active anti-cancer agents, namely cephalostatins/ ritterazines. The achievement of synthesizing a gram-scaled prodrug with comparable activity to the potent natural cephalostatins using green methods is our primary target. These synthetic methods can be scaled up based on the symmetrical coupling (SC) of two steroidal units of the same type. Our secondary target is the discovery of new green pathways that help in structural reconstruction programming toward the total synthesis of at least one potentially active family member. The strategy is based on functional group interconversions with high flexibility and brevity using green selective methods. The introduction of controlling groups using nontrivial reconstruction methodologies forms the backbone of our work. After certain modifications to the symmetrical BSP starting material, the resulting analogs underwent several chemoselective transformations through three main routes in rings F, D, and C. One of these routes is the chemoselective spiroketal opening (ring-F). The second route was the functionalization of the ∆14,15 bond (ring-D), including chlorination/dechlorination, in addition to epoxidation/ oxygenation processes. Finally, the introduction of the C-11 methoxy group as a directing group on ring-C led to several chemoselective transformations. Moreover, certain transformations on C-12 (ring-C), such as methylenation, followed by hydroboration-oxidation, led to a potentially active analog. The alignment of these results directs us toward the targets. Our efforts culminated in preparing effective anti-cancer prodrugs (8, 24, 30, and 31), which are able to overcome cancer drug resistance (chemoresistance) by inducing the atypical endoplasmic reticulum-mediated apoptosis pathway, which works through the release of Smac/Diablo and the activation of caspase-4.

Leptomeningeal disease (LMD) is a rare and lethal manifestation that may occur in the advanced stages of solid tumors and hematological malignancies. With advances in diagnostic techniques, the detection and confirmation of the presence of LMD have increased. Although its optimal treatment remains a challenge, the use of the intrathecal route for the delivery of novel therapeutics is now considered a promising drug delivery strategy to complement radiation and systemic-based therapies. Although methotrexate, cytarabine, and thiotepa have a long history in the treatment of LMD, other medications have also been shown to be beneficial. In this article, we have reviewed the effects of novel medications administered via the intrathecal route for the treatment of solid tumors. We have searched PubMed, Scopus, and Google Scholar databases till the end of September 2021 using the following keywords: ''leptomeningeal disease'', ''leptomeningeal carcinomatosis'', ''leptomeningeal metastases'', ''solid tumors'', ''solid cancers'', and ''intrathecal''. Our literature findings have uncovered that most studies on LMD, which occurs secondary to solid cancers, are available as 'case reports', and few clinical trials have been conducted to date. Single-drug (monotherapy) or combination drug therapy, administered via the intrathecal route, especially in metastatic breast and lung cancer, has been shown to improve patients' symptoms and overall lifespan, while exhibiting a low and acceptable prevalence of side effects. However, judgments/conclusions about the effectiveness and safety of these drugs still require further clinical evaluation.

Gastrointestinal stromal tumour (GIST) is a common gastrointestinal sarcoma located in the stromal cells of the digestive tract, and molecular studies have revealed the pathogenesis of mutations in KIT and PDGFRA genes. Since imatinib opened the era of targeted therapy for GIST, tyrosine kinase inhibitors (TKIs) that can treat GIST have been developed successively. However, the lack of new drugs with satisfactory therapeutic standards has made addressing resistance a significant challenge for TKIs in the face of the resistance to first-line and second-line drugs. Therefore, we need to find as many drugs and new treatments that block mutated genes as possible. METHODS: We conducted a comprehensive collection of literature using databases, integrated and analysed the selected literature based on keywords and the comprehensive nature of the articles, and finally wrote articles based on the content of the studies. RESULTS: In this article, we first briefly explained the relationship between GIST and KIT/ PDGFRα and then introduced the related drug treatment. The research progress of TKIs was analyzed according to the resistance of the drugs. CONCLUSION: This article describes the research progress of some TKIs and provides a brief introduction to the currently approved TKIs and some drugs under investigation that may have better therapeutic effects, hoping to provide clues to the research of new drugs.

In this review, we emphasized important biomarkers, pathogenesis, and newly developed therapeutic approaches in the treatment of colorectal cancer (CRC). This includes a complete description of small-molecule inhibitors, phytopharmaceuticals with antiproliferative potential, monoclonal antibodies for targeted therapy, vaccinations as immunotherapeutic agents, and many innovative strategies to intervene in the interaction of oncogenic proteins. Many factors combine to determine the clinical behavior of colorectal cancer and it is still difficult to comprehend the molecular causes of a person's vulnerability to CRC. It is also challenging to identify the causes of the tumor's onset, progression, and responsiveness or resistance to antitumor treatment. Current recommendations for targeted medications are being updated by guidelines throughout the world in light of the growing number of high-quality clinical studies. So, being concerned about the aforementioned aspects, we have tried to present a summarized pathogenic view, including a brief description of biomarkers and an update of compounds with their underlying mechanisms that are currently under various stages of clinical testing. This will help to identify gaps or shortfalls that can be addressed in upcoming colorectal cancer research.

Prostate cancer is ranked second among the most common male cancers. Androgen deprivation therapy (ADT) has long been the first-line treatment and the basis for all other therapies, reducing circulating androgens to castration levels and preventing disease development. Nevertheless, ADT monotherapy may not always limit disease development, and even at low testosterone levels, hormone-sensitive prostate cancer will become castration-resistant. Recent research demonstrates that prostate cancer can have a range of potentially actionable genetic abnormalities; no medications that target these variations have yet been shown to elicit therapeutic advantages. Despite their established efficacy in the management of other cancers, advanced genetic or immunological approaches are not regularly used to treat prostate cancer patients. As a result, there is an unmet demand for medicines that offer a better chance of survival than the existing castration-resistance prostate cancer (CRPC) therapy regimens. The use of oligodeoxynucleotides (ODN) and peptides in decoy technology have been developed as novel therapeutic approaches. Decoy ODNs bind to a particular transcription factor with high affinity and may suppress gene transcription. Peptide decoys bind to specific ligands with high specificity and inhibit signaling pathways. Recent evidence supports the notion that these techniques are promising and attractive in the fight against cancer. In the present review, we discuss the use of decoy technology as a novel therapeutic approach against prostate cancer.

AIM: After the balloon angioplasty, vascular adventitia fibroblasts (VAFs), which proliferate, trans-differentiate to myofibroblasts and migrate to neointima, are crucial in restenosis. Resveratrol (RSV) has been reported to protect the cardiovascular by reducing restenosis and the mechanism remains unclear. METHOD: This study was dedicated to investigate the effect of RSV on VAFs in injured arteries and explore the potential mechanism. In this work, carotid artery balloon angioplasty was performed on male SD rats to ensure the injury of intima and VAFs were isolated to explore the effects in vitro. The functional and morphological results showed the peripheral delivery of RSV decreased restenosis of the injured arteries and suppressed the expression of proliferation, migration and transformation related genes. Moreover, after being treated with RSV, the proliferation, migration and trans-differentiation of VAFs were significantly suppressed and exogenous TGF-β1 can reverse this effect. RESULT: Mechanistically, RSV administration activated SIRT1 and decreased the translation and expression of TGF-β1, SMAD3 and NOX4, and reactive oxygen species (ROS) decreased significantly after VAFs treated with RSV. CONCLUSION: Above results indicated RSV inhibited restenosis after balloon angioplasty through suppressing proliferation, migration and trans-differentiation of VAFs via regulating SIRT1- TGF-β1-SMAD3-NOX4 to decrease ROS.

Astrocytes are a multifunctional subset of glial cells that are important in maintaining the health and function of the central nervous system (CNS). Reactive astrocytes may release inflammatory mediators, chemokines, and cytokines, as well as neurotrophic factors. There may be neuroprotective (e.g., cytokines, like IL-6 and TGF-b) and neurotoxic effects (e.g., IL-1β and TNF-a) associated with these molecules. In response to CNS pathologies, astrocytes go to a state called astrogliosis which produces diverse and heterogenic functions specific to the pathology. Astrogliosis has been linked to the progression of many neurodegenerative disorders. Phytochemicals are a large group of compounds derived from natural herbs with health benefits. This review will summarize how several phytochemicals affect neurodegenerative diseases (e.g., Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and Parkinson's disease) in basic medical and clinical studies and how they might affect astrogliosis in the process.

This patent describes the synthesis of compounds, methods, and compositions for preventing, treating, and/or curing Covid-19, human coronavirus, and enterovirus infections. Some peptidomimetic compounds are very potent and could be a game changer in new treatment therapy for COVID-19.