The phosphate prodrug approach has emerged as a viable option for increasing the bioavailability of a drug candidate with low hydrophilicity and poor cell membrane permeability. When a phosphoric acid moiety is attached to the parent drug, it results in a several-fold elevation in aqueous solubility which helps to achieve desired bioavailability of the pharmaceutically active parental molecule. The neutral phosphate prodrugs have rapid diffusion ability through the plasma membrane as compared to their charged counterpart. The presence of phosphate mono ester breaking alkaline phosphatase (ALP) enzyme throughout the whole human body, is the main consideration behind the development of phosphate prodrug strategy. The popularity of this phosphate prodrug strategy is increasing nowadays due to the fulfillment of different desired pharmacokinetic characteristics required to get pharmaceutical and therapeutic responses without showing any serious adverse drug reactions (ADR). This review article mainly focuses on various phosphate prodrugs synthesized within the last decade to get an improved pharmacological response of the parent moiety along with various preclinical and clinical challenges associated with this approach. Emphasis is also given to the chemical mechanism to release the parent moiety from the prodrug.

The fibrosis of tissues and organs occurs via an aberrant tissue remodeling process characterized by an excessive deposition of extracellular matrix, which can lead to organ dysfunction, organ failure, and death. Because the pathogenesis of fibrosis remains unclear and elusive, there is currently no medication to reverse it; hence, this process deserves further study. Activating protein-1 (AP-1)-comprising Jun (c-Jun, JunB, JunD), Fos (c-fos, FosB, Fra1, and Fra2), and activating transcription factor-is a versatile dimeric transcription factor. Numerous studies have demonstrated that AP-1 plays a crucial role in advancing tissue and organ fibrosis via induction of the expression of fibrotic molecules and activating fibroblasts. This review focuses on the role of AP-1 in a range of fibrotic disorders as well as on the antifibrotic effects of AP-1 inhibitors. It also discusses the potential of AP-1 as a new therapeutic target in conditions involving tissue and organ fibrosis.

The topoisomerases (TOPO) play indispensable roles in DNA metabolism, by regulating the topological state of DNA. Topoisomerase I and II are the well-established drug-targets for the development of anticancer agents and antibiotics. These drugs-targeting enzymes have been used to establish the relationship between drug-stimulated DNA cleavable complex formation and cytotoxicity. Some anticancer drugs (such as camptothecin, anthracyclines, mitoxantrone) are also widely used as Topo I and Topo II inhibitors, but the poor water solubility, myeloma suppression, dose-dependent cardiotoxicity, and multidrug resistance (MDR) limited their prolong use as therapeutics. Also, most of these agents displayed selective inhibition only against Topo I or II. In recent years, researchers focus on the design and synthesis of the dual Topo I and II inhibitors, or the discovery of the dual Topo I and II inhibitors from natural products. Shikonin (a natural compound with anthraquinone skeleton, isolated from the roots of Lithospermum erythrorhizon) has drawn much attention due to its wide spectrum of anticancer activities, especially due to its dual Topo inhibitive performance, and without the adverse side effects, and different kinds of shikonin derivatives have been synthesized as TOPO inhibitors for the development of anticancer agents. In this review, the progress of the shikonin and its derivatives together with their anticancer activities, anticancer mechanism, and their structure-activity relationship (SAR) was comprehensively summarized by searching the CNKI, PubMed, Web of Science, Scopus, and Google Scholar databases.

BACKGROUND: Berberine is the main active compound of different herbs and is defined as an isoquinoline quaternary botanical alkaloid found in barks and roots of numerous plants. It exhibits a wide range of pharmacological effects, such as anti-obesity and antidiabetic effects. Berberine has antibacterial activity against a variety of microbiota, including many bacterial species, protozoa, plasmodia, fungi, and trypanosomes. OBJECTIVE: This review describes the role of berberine and its metabolic effects. It also discussed how it plays a role in glucose metabolism, fat metabolism, weight loss, how it modulates the gut microbiota, and what are its antimicrobial properties along with its potential side effects with maximal tolerable dosage. METHODS: Representative studies were considered and analyzed from different scientific databases, including PubMed and Web of Science, for the years 1982-2022. RESULTS: Literature analysis shows that berberine affects many biochemical and pharmacological pathways that theoretically yield a positive effect on health and disease. Berberine exhibits neuroprotective properties in various neurodegenerative and neuropsychological ailments. Despite its low bioavailability after oral administration, a plant alkaloid is a promising tool for several disorders. A possible hypothesis would be the modulation of the gut microbiome. While the evidence concerning the aging process in humans is more limited, preliminary studies have shown positive effects in several models. CONCLUSION: Berberine could serve as a potential candidate for the treatment of several diseases. Previous literature has provided a basis for scientists to establish clinical trials in humans. However, for obesity, the evidence appears to be sufficient for hands-on use.

Although the burden of malaria has been successfully controlled globally, this disease remains a major public health issue. To date, neither existing drugs nor vaccines against malaria are sufficient in eliminating malaria worldwide. To achieve the eradication of malaria by 2040, effective interventions targeting all Plasmodium species are urgently needed. As the cornerstone of vaccine design, immune memory serves a significant role in the host's defense against Plasmodium infections. It has long been considered that innate immunity is non-specific and lacks immunologic memory. However, emerging evidence has suggested that innate immunity can be trained following exposure of the body to infectious agents, such as Plasmodium or its products, which, in turn, promotes the onset of a type of memory in innate immune cells. The above ''trained'' innate immune cells, whose phenotype is modified in response to epigenetic modifications, metabolic recombination, or cytokine secretion, exhibit differential pathophysiology after the exposure of the body to a pathogen. In addition, Plasmodium-infected red blood cells and other host cells can secrete exosomes that contain conserved parasite-specific information, such as proteins, RNA, non-coding RNA molecules, and nucleic acids. These molecules can act as stimuli for promoting the establishment of ''trained'' innate immunity against malaria, thereby altering the onset and progression of the parasitic disease. A deeper understanding of the role of exosomes in the development of ''trained'' innate immunity during Plasmodium infection could provide novel therapeutic and prevention strategies against malaria infections.

BACKGROUND: Elevated concentrations of serum uric acid (SUA) are associated with several conditions, including cardiovascular disease. The present study aimed to estimate the impact of statin therapy on SUA levels through a systematic review and meta-analysis of clinical trials. METHODS: PubMed, Embase, Web of Science, and Scopus were searched on January 14, 2022, to identify eligible clinical trials. The intervention group received statins as monotherapy or in combination with other drugs, and the control group received non-statins or placebo. Studies reporting SUA levels before and after treatment were selected for further analysis. Finally, the data were pooled, and the mean changes in SUA, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides were reported. RESULTS: Out of 1269 identified studies, 23 were included in the review. A total of 3928 participants received statin therapy, and 1294 were included in control groups. We found a significant reduction in SUA levels following statin therapy (mean difference (MD) = -26.67 μmol/L with 95% confidence interval (CI) [-44.75, -8.60] (P = 0.004)). Atorvastatin (MD = -37.93 μmol/L [-67.71, -8.15]; P < 0.0001), pravastatin (MD = -12.64 μmol/L [-18.64, -6.65]; P < 0.0001), and simvastatin (MD = -5.95 μmol/L [-6.14, -5.80]; P < 0.0001), but not rosuvastatin, were significantly associated with a reduction in SUA levels. An analysis comparing different types of statins showed that pravastatin 20-40 mg/day could significantly reduce SUA when compared to simvastatin 10-20 mg/day (-21.86 μmol/L [-36.33,-7.39]; P = 0.003). CONCLUSION: Statins were significantly associated with a decrease in SUA levels, particularly atorvastatin, which was found to be most effective in lowering SUA. Atorvastatin may be the most appropriate cholesterol-lowering agent for patients with or at risk of hyperuricemia.

BACKGROUND: Coronavirus-19 disease (Covid-19) is an infection with high morbidity and mortality. Obesity and low body mass index (BMI) have both been linked to severe Covid-19, but recent studies have failed to confirm these associations. OBJECTIVES: The aim of this study was to examine the relationship between BMI and disease progression in hospitalised patients with Covid-19. METHODS: We performed a monocentric, retrospective observational study at the Fondazione Policlinico Gemelli in Rome. We enrolled 1544 (977 men) patients who presented to the emergency department with a positive Covid-19 test between January and December 2021. We divided patients into five classes based on BMI. Demographic, clinical, laboratory, and radiological data were collected for all patients. RESULTS: Of the 1544 patients, 1297 recovered after hospitalization, whereas 247 (16%) died. Of those who died, 16/247 (6.5%) had a BMI below18.5 kg/m2, 72/247 (29%) had a BMI between 18.5 and 24.99 kg/m2, 103/247 (42%) had a BMI between 25 and 29.99 kg/m2, 36/247 (15%) had a BMI between 30 and 35 kg/m2, and 20/247 (8%) had a BMI above 35 kg/m2. After adjusting the results for age, sex, and concomitant diseases using multivariate logistic regression, we found a significantly increased risk of intensive care unit (ICU) admission in severely obese patients (BMI > 35) compared to normal weight patients (BMI: 18.5-24.99) (p > 0.001). Mortality was not associated with BMI. CONCLUSION: We confirm that severe obesity is a risk factor for ICU admission in patients with Covid-19. No association was found between BMI and mortality.

Heparin, as a glycosaminoglycan, is known for its anticoagulant and antithrombotic properties for several decades. Heparin is a life-saving drug and is widely used for anticoagulation in medical practice. In recent years, there have been extensive studies that heparin plays an important role in non-anticoagulant diseases, such as anti-inflammatory, anti-viral, anti-angiogenesis, anti-neoplastic, anti-metastatic effects, and so on. Clinical observation and in vitro experiments indicate that heparin displays a potential multi-target effect. In this brief review, we will summarize heparin and its derivative's recently studied progress for the treatment of various viral infections. The aim is to maximize the benefits of drugs through medically targeted development, to meet the unmet clinical needs of serious viral diseases.

Tyrosine is an enzyme responsible for melanin production. Its abnormal accumulation in different parts of the body is known as hyperpigmentation. Tyrosinase inhibitors have been used as one of the main approaches to treat these kinds of cosmetic and medical issues. This review aimed to discuss the advances in patents for this class of inhibitors, focusing on synthetic ones, by studying recent patent applications (2012-2022). We performed a screening using the European Patent Office's Espacenet database, from which 15 inventions were selected and fully studied. China has more patent applications, all of them were focused on synthetic methods and the majority declared at least two additional applications as antibrowning agents for fruits and vegetables, biological pesticides, and medicine to treat diseases like Parkinson's or melanoma. The strategies employed by the investigators focused on the examination of previous literature, which oriented on the type of structures that have been found to show good inhibitory activity; the study also examined aspects of their reaction mechanisms and information about the structure-activity relationship. For some groups of inhibitors, such as benzaldehyde and anthraquinone derivatives, the data were meaningful and extensive. In contrast, arginyl and troponoids compounds were difficult to analyze due to the limited research works.

BACKGROUND: Coenzyme Q (CoQ) is an enzyme family that plays a crucial role in maintaining the electron transport chain and antioxidant defense. CoQ10 is the most common form of CoQ in humans. A deficiency of CoQ10 occurs naturally with aging and may contribute to the development or progression of many diseases. Besides, certain drugs, in particular, statins and bisphosphonates, interfere with the enzymes responsible for CoQ10 biosynthesis and, thus, lead to CoQ10deficiency. OBJECTIVES: This article aims to evaluate the cumulative studies and insights on the topic of CoQ10 functions in human health, focusing on a potential role in maintaining physical activity and extending the life cycle. RESULTS: Although supplementation with CoQ10offers many benefits to patients with cardiovascular disease, it appears to add little value to patients suffering from statin-associated muscular symptoms. This may be attributed to substantial heterogeneity in doses and treatment regimens used. CONCLUSION: Therefore, there is a need for further studies involving a greater number of patients to clarify the benefits of adjuvant therapy with CoQ10 in a range of health conditions and diseases.

Molecules containing triazolopyrimidine core showed diverse biological activities, including anti-Alzheimer, antidiabetes, anticancer, antimicrobial, antituberculosis, antiviral, antimalarial, anti-inflammatory, anti-parkinsonism activities, and treatment of glaucoma. Triazolopyrimidines have around 8 isomeric structures including the most stable 1,2,4-triazolo[1,5-a] pyrimidine ones. Triazolopyrimidines were obtained by using various chemical reactions, among them a) 1,2,4-triazole nucleus annulation to pyrimidine, b) pyrimidines annulation to 1,2,4-triazole structure, c) 1,2,4-triazolo[l,5-a] pyrimidines rearrangement, and d) pyrimido-tetrazine rearrangement. This review discusses synthetic methods, recent pharmacological actions and drug delivery perspectives of triazolopyrimidines.

BACKGROUND: Familial hypercholesterolemia (FH) is a prevalent and potentially fatal illness that causes a substantial elevation in low-density lipoprotein cholesterol (LDL-C). OBJECTIVE: The aim of this study was to investigate the effects of monoclonal antibodies alirocumab and evolocumab on LDL-C and other lipid parameters, as well as their safety in familial hypercholesterolemia patients. METHODS: A comprehensive search was done on PubMed/MEDLINE, EMBASE, Web of Science (WOS/ ISI), Scopus, ClinicalTrials (www. CLINICALTRIALS: gov), and conferences/ congress research papers. Random effect models were used to calculate mean differences (%) and risk ratios (RRs), and confidence intervals (95%). RESULTS: Ten studies (n=1489 patients) were included in this study. PCSK9 inhibitors decreased the levels of LDL-C by -49.59% (95%CI -55.5%, -43.67%) as compared to placebo. They also didn't alter the Treatment-Emergent Adverse Event (TEAE) and neuronal events by RR 0.92 (0.75, 1.13) and 1.31 (0.66, 2.59), respectively. PCSK9 inhibitors were effective and safe in treating patients with FH. CONCLUSION: There was high-quality evidence showing that monoclonal antibodies (alirocumab & evolocumab) lower LDL-C (GRADE: high), lipoprotein (a) (GRADE: High), triglycerides (TG) (GRADE: High), total cholesterol (GRADE: High), non-high-density lipoprotein cholesterol (nonHDL-C) (GRADE: Moderate), and apolipoprotein B (GRADE: High), and increase the HDL-C (GRADE: High) as well as apolipoprotein A1 (GRADE: High). Comparing PCSK9 inhibitors against placebo, neither TEAE (GRADE: high) nor neuronal events (GRADE: moderate) were changed. Registration number PROSPERO-CRD42022334035.

BACKGROUND: Quinoa (Chenopodium quinoa) has a structure similar to whole grains and contains phytochemicals and dietary fiber. Hence, it is considered a food substance with a high nutritional value. OBJECTIVE: The purpose of the present study was to assess the efficacy of quinoa in reducing fasting blood glucose (FBG), body weight (BW), and body mass index (BMI) in a meta-analysis of randomized clinical trials. METHODS: A comprehensive search in ISI Web of Science, Scopus, and PubMed databases as well as Google Scholar, was conducted up to November 2022 to identify reports of randomized clinical trials that investigated the effect of quinoa on FBG, BW, and BMI. RESULTS: Seven trials comprising 258 adults with mean ages of 31 to 64 years were included in this review. Studies used 15 to 50 grams of quinoa/per day as an intervention, and the intervention was between 28 to 180 days. In a dose-response analysis of FBG, there was significant evidence of a nonlinear association between intervention and FBG based on the quadratic model (P-value for nonlinearity= 0.027); hence, the slope of the curve increased when quinoa intake was nearly 25 g/day. In comparison between quinoa seed supplementation and placebo, our findings showed that quinoa seed supplementation did not have a significant effect on BMI (MD: -0.25; 95% CI: -0.98, 0.47; I2=0%, P=0.998) and BW (MD: -0.54; 95% CI: -3.05, 1.97; I2=0%, P=0.99), when compared with placebo. Evidence of publication bias was not found among the included studies. CONCLUSION: The present analysis revealed the beneficial effects of quinoa on the blood glucose level. Further studies on quinoa are needed to confirm these results.

BACKGROUND: During the COVID-19 pandemic, people suffered from major mental health problems. These include stress, anxiety, and confusion about the existing situation of home confinement. Melatonin is a popular anti-inflammatory and antioxidant molecule sold as an over-the-counter dietary supplement. OBJECTIVE: This review discusses the indications for using melatonin in the context of the COVID-19 pandemic, including treatment. METHODS: A comprehensive search of publications was conducted in electronic databases focusing on the administration of melatonin in COVID-19. RESULTS: Stress has a huge negative impact on sleep routines and the quality of life of individuals. Sleep is considered an important modulator of the immune response. Thus, a lack of sleep can weaken immunity, increasing organism susceptibility to infection. For instance, shorter sleep durations are associated with a rise in suffering from the common cold. The administration of melatonin protects against viral and other pathogens and speeds clinical recovery. CONCLUSION: In patients admitted to intensive care units, melatonin decreases the risks of severe complications, such as thrombosis and sepsis, and mortality rates. In addition, it is efficacious in lowering vessel permeability, depression, and sedation, and improving the quality of sleep, which could also help COVID-19 patients achieve better clinical outcomes.

Schiff bases represent a valuable class of organic compounds, synthesized via condensation of primary amines with ketones or aldehydes. They are renowned for possessing innumerable applications in agricultural chemistry, organic synthesis, chemical and biological sensing, coating, polymer and resin industries, catalysis, coordination chemistry, and drug designing. Schiff bases contain imine or azomethine (-C=N-) functional groups which are important pharmacophores for the design and synthesis of lead bioactive compounds. In medicinal chemistry, Schiff bases have attracted immense attention due to their diverse biological activities. This review aims to encompass the recent developments on the antimicrobial activities of Schiff bases. The article summarizes the antibacterial, antifungal, antiviral, antimalarial, and antileishmanial activities of Schiff bases reported since 2011.

Epilepsy is a chronic neurological degenerative disease with a high incidence, affecting all age groups. Refractory Epilepsy (RE) occurs in approximately 30-40% of cases with a higher risk of sudden unexpected death in epilepsy (SUDEP). Recent studies have shown that spontaneous seizures developed in epilepsy can be related to an increase in oxidative stress and reactive oxygen derivatives (ROS) production. Increasing ROS concentration causes lipid peroxidation, protein oxidation, destruction of nuclear genetic material, enzyme inhibition, and cell death by a mechanism known as "ferroptosis" (Fts). Inactivation of glutathione peroxidase 4 (GPX4) induces Fts, while oxidative stress is linked with increased intracellular free iron (Fe+2) concentration. Fts is also a non-apoptotic programmed cell death mechanism, where a hypoxia-inducible factor 1 alpha (HIF-141) dependent hypoxic stress-like condition appears to occur with accumulation of iron and cytotoxic ROS in affected cells. Assuming convulsive crises as hypoxic stress, repetitive convulsive/hypoxic stress can be an effective inducer of the "epileptic heart" (EH), which is characterized by altered autonomic function and a high risk of malignant or fatal bradycardia. We previously reported that experimental recurrent seizures induce cardiomyocyte Fts associated with SUDEP. Furthermore, several genes related to Fts and hypoxia have recently been identified in acute myocardial infarction. An emerging theme from recent studies indicates that inhibition of GPX4 through modulating expression or activities of the xCT antiporter system (SLC7A11) governs cell sensitivity to oxidative stress from ferroptosis. Furthermore, during hypoxia, an increased expression of stress transcriptional factor ATF3 can promote Fts induced by erastin in a HIF-141-dependent manner. We propose that inhibition of Fts with ROS scavengers, iron chelators, antioxidants, and transaminase inhibitors could provide a therapeutic effect in epilepsy and improve the prognosis of SUDEP risk by protecting the heart from ferroptosis.

Objective The primary goal of the present study was to measure the implications of hypoxemia in COVID-19 patients with a history of coronary artery disease (CAD). Methods A systematic search of the literature published from November 1, 2019 to May 1, 2021, was conducted on PubMed/MEDLINE, Embase, and Web of Science databases. Afterwards, an observational study was designed based on the electronic health records of COVID-19 patients hospitalized in a tertiary referral hospital during the same period. A total of 179 COVID-19 cases were divided into two groups: cases with a history of CAD and percutaneous coronary intervention (CAD/PCI+, n = 89) and controls (n = 90). Clinical data were extracted from the electronic database of the hospital and statistically analyzed. Results After the application of inclusion/exclusion criteria, only three studies were deemed eligible, one of which was concerned with the impact of CAD on the all-cause mortality of COVID-19. Results from our observational study indicated that the cases were older (median age: 74 vs. 45) and more likely to develop hypoxemia (25.8% vs. 8.8%) than the controls. CAD/PCI+ was correlated with a more severe COVID-19 (11% vs. 1%). Age was a moderately significant independent predictor of increased COVID-19 severity, while hypoxemia was not. Conclusion Considering the negative impact of hypoxemia on the prognosis of COVID-19 and its higher prevalence among COVID-19 patients with underlying CAD, further research is warranted to unravel the negative effects of COVID-19 on the mechanisms of gas exchange and delivery in patients with pre-existing CAD.

Xanthones are widely distributed polyphenols, present commonly in higher plants; Garcinia, Calophyllum, Hypericum, Platonia, Mangifera, Gentiana and Swertia. Xanthone tricyclic scaffold is able to interact with different biological targets, showing antibacterial and cytotoxic effects, as well as potent effects against osteoarthritis, malaria, and cardiovascular diseases. Thus, in this article we focused on pharmacological effects, applications and preclinical studies with the recent updates of xanthon´s isolated compounds from 2017-2020. We found that only α-mangostin, gambogic acid, and mangiferin, have been subjected to preclinical studies with particular emphasis on the development of anticancer, diabetes, antimicrobial and hepatoprotective therapeutics. Molecular docking calculations were performed to predict the binding affinities of xanthone-derived compounds against SARS-CoV-2 Mpro. According to the results, cratoxanthone E and morellic acid demonstrated promising binding affinities towards SARS-CoV-2 Mpro with docking scores of −11.2 and −11.0 kcal/mol, respectively. Binding features manifested the capability of cratoxanthone E and morellic acid to exhibit nine and five hydrogen bonds, respectively, with the key amino acids of the Mpro active site. In conclusion, cratoxanthone E and morellic acid are promising anti-COVID-19 drug candidates that warrant further detailed in vivo experimental estimation and clinical assessment.

BACKGROUND: The indiscriminate use of antibiotics brings an alarming reality: in 2050, bacterial resistance could be the main cause of death in the world, resulting in the death of 10 million people, according to the World Health Organization (WHO). In this sense, to combat bacterial resistance, several natural substances, including chalcones, have been described in relation to antibacterial, representing a potential tool for the discovery of new antibacterial drugs. OBJECTIVE: The objective of this study is to perform a bibliographic survey and discuss the main contributions in the literature about the antibacterial potential of chalcones in the last 5 years. METHOD: A search was carried out in the main repositories, for which the publications of the last 5 years were investigated and discussed. Unprecedented in this review, in addition to the bibliographic survey, molecular docking studies were carried out to exemplify the applicability of using one of the molecular targets for the design of new entities with antibacterial activity. RESULTS: In the last 5 years, antibacterial activities were reported for several types of chalcones, for which activities were observed for both gram-positive and gram-negative bacteria with high potency, including MIC values in the nanomolar range. Molecular docking simulations demonstrated important intermolecular interactions between chalcones and residues from the enzymatic cavity of the enzyme DNA gyrase, one of the validated molecular targets in the development of new antibacterial agents. CONCLUSION: The data presented demonstrate the potential of using chalcones in drug development programs with antibacterial properties, which may be useful to combat resistance, a worldwide public health problem.

To date, it is well known that a significant number of diseases of cardiovascular genesis (coronary heart disease, myocardial infarction, cardiomyopathy, Takotsubo syndrome, heart failure, etc.) and extra-cardiac genesis (renal failure, chronic obstructive pulmonary disease, sepsis, diabetes mellitus, etc.) cause injury to contractile cells of the heart muscle (myocardial cells). The most sensitive and specific criteria for proving myocardial cell injury are cardiospecific troponins (CSTns) - CSTnI and CSTnT. According to the current clinical recommendations of the European, American, and Russian Cardiological Communities, CSTnI and CSTnT are the main biomarkers for early diagnosis of myocardial infarction. Hypertension is one of the most dangerous and common risk factors for the development of cardiovascular pathologies and is associated with a high risk of dangerous cardiovascular complications. Therefore, there is an urgent need to search for new biomarkers for the timely assessment of the prognosis of patients with hypertension. Objective: This mini-review aims to substantiate the possibilities of using the cardiomarkers (CSTnI and CSTnT) to assess the prognosis of patients suffering from hypertension and to discuss potential mechanisms that cause injury to myocardial cells and increase serum levels of CSTnI and CSTnT. Materials and methods. This is a narrative mini-review, which was prepared using the following databases: Pubmed/Medline, PubMed Central, Embase, Scopus, and Web of Science. The following keywords were used in the literature search: "myocardial cells", "injury", "damage", and "hypertension" in combination with the terms "mechanisms of injury" "predictive significance", "cardiac troponins", or "cardiospecific troponins".

Patients with diabetes are at higher risk of cognitive impairment and memory loss than the normal population. Thus, using hypoglycemic agents to improve brain function is important for diabetic patients. Sodium-glucose cotransporters-2 inhibitors (SGLT2i) are a class of therapeutic agents used in the management of diabetes that has some pharmacologic effects enabling them to fight against the onset and progress of memory deficits. Although the exact mediating pathways are not well understood, emerging evidence suggests that SGLT2 inhibition is associated with improved brain function. This study reviewed the possible mechanisms and provided evidence suggesting SGLT2 inhibitors could ameliorate cognitive deficits.

Familial hypercholesterolemia (FH) is an autosomal dominant inheritable disease with severe disorders of lipid metabolism. It is mainly marked by increasing levels of plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), xanthoma, corneal arch, and early-onset coronary heart disease (CHD). The prevalence of FH is high, and it is dangerous and clinically underdiagnosed. The clinical treatment for familial hypercholesterolemia includes both pharmacological and non-pharmacological treatment, of which non-pharmacological treatment mainly includes therapeutic lifestyle change and dietary therapy, LDL apheresis, liver transplantation and gene therapy. In recent years, many novel drugs have been developed to treat familial hypercholesterolemia more effectively. In addition, the continuous maturity of non-pharmacological treatment techniques has also brought more hope for the treatment of FH. This paper analyzes the pathogenic mechanism and the progress in clinical treatment of familial hypercholesterolemia. Furthermore, it also summarizes the mechanism and structure-activity relationship of FH therapeutic drugs that have been marketed. In a word, this article provides a reference value for the research and development of FH therapeutic drugs.

Vitiligo is a disease characterized by skin discoloration, and no safe and effective drugs have been developed until now. New drug research and development are imminent. This article reviews the research on small-molecule drugs for vitiligo from 1990 to 2021 at home and abroad. They are classified according to their structures and mechanisms of action, including natural products and derivatives, anti-oxidative stress drugs, immunosuppressants, prostaglandins, etc. The research on their anti-vitiligo activity, structural modification, new dosage forms, clinical trials, and the development trend in new anti-vitiligo drugs are reviewed, which provides important references for the development of new drugs.

The term "gynecological cancer" is used for a group of cancers occurring in the female reproductive system. Some of these cancers are ranked as the leading causes of death in developed and developing countries. The lack of proper diagnostic strategies is one of the most important reasons that make them lethal. PIWI-interacting RNAs or piRNAs are a class of small non-coding RNAs, which contain 24-32 nucleotides. These RNAs take part in some cellular mechanisms, and their role in diverse kinds of cancer is confirmed by accumulative evidence. In this review, we gather some information on the roles of these RNAs and members of the PIWI protein family to provide new insight into accurate diagnostic biomarkers and more effective anti-cancer drugs with fewer side effects.

mTOR: mammalian/mechanistic target of rapamycin; SMA: spinal muscular atrophy; IGF-1R: insulin-like growth factor type 1 receptor; FOXO3A: Forkhead box class O 3A; eIF4EBP1: eukaryotic translation initiation factor 4E-binding protein 1; Atrogin-1 (FBOX32): atrophy gene-1 (F-box only protein 32); TRAF2: TNF receptor-associated factor 2; p38 (MAPK14): p38 (mitogen-activated protein kinase 14); RRAS2: RAS related 2; ERK (MAPK1): extracellular signal-regulated kinase 1/2 (mitogen-activated protein kinase 1); SBMA: spinal and bulbar muscular atrophy; SMN: survival motor neuron; Akt: protein kinase B; MAFbx/atrogin-1: muscle atrophy F-box; MuRF-1: muscle RING-finger protein-1; WT: wild-type; GC-KLF15-BCAA: circadian glucocorticoid-Krüppel-like factor 15-branched-chain amino acid; SBMA: spinal and bulbar muscular atrophy; PGC1α: proliferator-activated receptor γ coactivator 1 alpha CTRP3: C1q/TNF-related protein 3; SMN: survival motor neuron; VEGF: vascular endothelial growth factor; PTEN: phosphatase and tensin homolog.

Coronary atherosclerotic disease (CAD) is a common cardiovascular disease and an important cause of death. Moreover, endothelial cells (ECs) injury is an early pathophysiological feature of CAD, and long noncoding RNAs (lncRNAs) can modulate gene expression. Recent studies have shown that lncRNAs are involved in the pathogenesis of CAD, especially by regulating ECs. In this review, we summarize the novel progress of lncRNA-modulated ECs in the pathogenesis of CAD, including ECs proliferation, migration, adhesion, angiogenesis, inflammation, apoptosis, autophagy, and pyroptosis. Thus, as lncRNAs regulate ECs in CAD, lncRNAs will provide ideal and novel targets for the diagnosis and drug therapy of CAD.

High-density lipoproteins (HDL) have been shown to exert multiple cardioprotective and antidiabetic functions, such as their ability to promote cellular cholesterol efflux and their antioxidant, anti-inflammatory, and antiapoptotic properties. Type 2 diabetes (T2D) is usually associated with low high-density lipoprotein cholesterol (HDL-C) levels as well as with significant alterations in the HDL composition, thereby impairing its main functions. HDL dysfunction also negatively impacts both pancreatic β-cell function and skeletal muscle insulin sensitivity, perpetuating this adverse self-feeding cycle. The impairment of these pathways is partly dependent on cellular ATP-binding cassette transporter (ABC) A1-mediated efflux to lipid-poor apolipoprotein (apo) A-I in the extracellular space. In line with these findings, experimental interventions aimed at improving HDL functions, such as infusions of synthetic HDL or lipid-poor apoA-I, significantly improved glycemic control in T2D patients and experimental models of the disease. Cholesteryl ester transfer protein (CETP) inhibitors are specific drugs designed to increase HDL-C and HDL functions. Posthoc analyses of large clinical trials with CETP inhibitors have demonstrated their potential anti-diabetic properties. Research on HDL functionality and HDL-based therapies could be a crucial step toward improved glycemic control in T2D subjects.