The average worldwide human life expectancy is 70 years, with a significantly higher value in Western societies. Many modern diseases are not associated with premature mortality but with a decreased quality of life in aged patients and an excessive accumulation of various toxic compounds in the human body during life. Today, scientists are especially interested in finding compounds that can help increase a healthy lifespan by detoxifying the body. Phytotherapy with specific approaches is used in alternative medicine to remove toxins from the body. Worldwide, research is conducted to identify medicinal plant-derived molecules that, with few or no side effects, may protect the liver and other organs. This review provides updated information about the detoxification process, the traditional and modern use of the most effective medicinal plants, their active metabolites as detoxifying agents, and the mechanisms and pathways involved in the detoxification process. Among medicinal plants with substantial detoxifying properties, a major part belongs to the Asteraceae family (Silybum marianum, Cynara scolymus, Arctium lappa, Helichrysum spp, Inula helenium, and Taraxacum officinale). The most widely used hepatoprotective phytocomponent is silymarin, a standardized extract from the Silybum marianum seeds containing a mixture of flavonolignans. Many polysaccharides, polyphenols, and terpenoids have a detoxifying effect. Overall, scientific data on medicinal plants used in phytotherapeutic practice worldwide provides an understanding and awareness of their efficacy in detoxification.

Coronary artery disease exhibits a growing mortality and morbidity worldwide despite the advances in pharmacotherapy and coronary intervention. Coronary artery disease is classified as the acute coronary syndromes and chronic coronary syndromes according to the most recent guidelines of the European Society of Cardiology. Antithrombotic treatment is the cornerstone of therapy in coronary artery disease due to the involvement of atherothrombosis in the pathophysiology of the disease. Administration of antiplatelet agents, anticoagulants and fibrinolytics reduce ischemic risk, which is amplified early post-acute coronary syndromes or post percutaneous coronary intervention; though, antithrombotic treatment increases the risk for bleeding. The balance between ischemic and bleeding risk is difficult to achieve and is affected by patient characteristics, procedural parameters, concomitant medications and pharmacologic characteristics of the antithrombotic agents. Several pharmacological strategies have been evaluated in patients with coronary artery disease, such as the effectiveness and safety of antithrombotic agents, optimal dual antiplatelet treatment schemes and duration, aspirin de-escalation strategies of dual antiplatelet regimens, dual inhibition pathway strategies as well as triple antithrombotic therapy. Future studies are needed in order to shed light on the gaps in our knowledge, including special populations.

Human health is significantly threatened by infectious diseases caused by viral infection. Over the years, there have been numerous virus epidemics worldwide, causing millions of deaths. Traditional antiviral medications have many problems, including poor solubility and antiviral resistance. Additionally, because different drug delivery methods have different biological barriers to overcome, the drug's bioavailability will be significantly affected. Therefore, it is essential that researchers create more effective antiviral drugs. To serve as a guide for the future development of nanosized antiviral drugs with stronger and more precise therapeutic effects, research has been performed on nanotechnology in the field of antiviral therapy. This review summarizes the recent developments in antiviral nanopharmaceuticals with different delivery routes. Research on 7 typical viruses, including COVID-19, has been included in this review. The literature contains 40% of studies on traditional drug delivery, 20% of research on innovative drug delivery techniques, and 40% of research on antiviral nanovaccines. After being loaded into nanoparticles, antiviral drugs can be delivered through several drug modes of delivery, overcoming biological barriers. Moreover, some nanoparticles themselves have the ability to combat infections, so they can be used in conjunction with antiviral medication. The use of nanoparticle medications through various routes of administration can result in their unique benefits. They can be capable of overcoming its limitations as well as retaining the advantages of this method of delivery. This will motivate researchers to conducted a new investigation on nanoparticle medicines from the standpoint of the route of administration in order to increase the practicability of antiviral medications.

A novel strategy that has the potential to solve the drawbacks of the present conventional vaccines is the development of DNA vaccines. DNA vaccines offer a versatile and adaptable platform for treating a wide variety of diseases, as immunization targets may be easily adjusted by altering the gene sequences encoded in the plasmid DNA delivered. Due to their ability to elicit both humoral and cellular immune responses, their stability, and the ease with which they may be produced, plasmid DNA vaccines are quickly becoming the vaccine of choice, they are frequently safer than conventional vaccinations. Despite the highly encouraging outcomes of ongoing clinical trials, these vaccines' immunogenicity is compromised by a few factors. The use of various vaccine delivery techniques, the use of various polymer-based carriers, and the use of adjuvants are some of the several approaches that might be examined to better the immunogenicity of DNA vaccines made from plasmids. These advancements taken together might allow plasmid DNA vaccines to be successfully used in clinical settings.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) have large individual differences, unclear risk stratification, and imperfect treatment plans. Risk prediction models are helpful for the dynamic assessment of patients' prognostic risk and early intensive therapy of high-risk patients. The purpose of this study is to systematically summarize the existing risk prediction models and novel prognostic factors for HFpEF, to provide a reference for the construction of convenient and efficient HFpEF risk prediction models. METHODS: Studies on risk prediction models and prognostic factors for HFpEF were systematically searched in relevant databases including PubMed and Embase. The retrieval time was from inception to February 1, 2023. The Quality in Prognosis Studies (QUIPS) tool was used to assess the risk of bias in included studies. The predictive value of risk prediction models for end outcomes was evaluated by sensitivity, specificity, the area under the curve, C-statistic, C-index, etc. In the literature screening process, potential novel prognostic factors with high value were explored. RESULTS: A total of 21 eligible HFpEF risk prediction models and 22 relevant studies were included. Except for 2 studies with a high risk of bias and 2 studies with a moderate risk of bias, other studies that proposed risk prediction models had a low risk of bias overall. Potential novel prognostic factors for HFpEF were classified and described in terms of demographic characteristics (age, sex, and race), lifestyle (physical activity, body mass index, weight change, and smoking history), laboratory tests (biomarkers), physical inspection (blood pressure, electrocardiogram, imaging examination), and comorbidities. CONCLUSION: It is of great significance to explore the potential novel prognostic factors of HFpEF and build a more convenient and efficient risk prediction model for improving the overall prognosis of patients. This review can provide a substantial reference for further research.

The blood-brain barrier (BBB) regulates blood and chemical exchange in the central nervous system. It is made up of brain parenchyma capillary endothelial cells. It separates the interstitial cerebrospinal fluid from the circulation and limits brain drug entry. Peptides, antibodies, and even tiny hydrophilic biomolecules cannot flow across the BBB due to their semi-permeability. It protects the brain from poisons, chemicals, and pathogens, and blood cells penetrate brain tissue. BBB-facilitated carrier molecules allow selective permeability of nutrients such as D-glucose, L-lactic acid, L-phenylalanine, L-arginine, and hormones, especially steroid hormones. Brain barriers prevent drug molecules from entering, making medication delivery difficult. Drugs can reach specific brain regions through the nasal cavity, making it a preferred route. The in- situ gels are mucoadhesive, which extends their stay in the nasal cavity, allows them to penetrate deep and makes them a dependable way of transporting numerous medications, including peptides and proteins, straight into the central nervous system. This approach holds great potential for neurological therapy as they deliver drugs directly to the central nervous system, with less interference and better drug release control. The brain affects daily life by processing sensory stimuli, controlling movement and behaviour, and sustaining mental, emotional, and cognitive functioning. Unlike systemic routes, the nasal mucosa is extensively vascularized and directly contacts olfactory sensory neurons. Compared to the systemic circulation, this improves brain bioavailability of medications. Drugs can be delivered to the brain using in-situ gel formulations safely and efficiently, with a greater therapeutic impact than with traditional techniques.

Allergies are a major health issue. Allergen avoidance, antihistamines, and corticosteroids do not treat the pathology's causes, therefore long-term therapy is essential. Long-term allergen-specific immunotherapy builds immune tolerance to the allergen. Unfortunately, immunotherapies for all allergens are not available, and adverse reactions during therapy, especially in severely allergic persons, remain a worry. In this regard, cell and bio- or nanomaterial-based allergy treatments are promising. This overview covers the most important tactics from these two strategies with examples. Nanotechnology encompasses science, engineering, and technology at 1-100 nm. Due to their one-of-a-kind characteristics, nanomaterials can be used in healthcare. Small molecules' chemical and physical properties are modified by the system's size, shape, content, and function. Toxicity and hypersensitivity reactions need to be evaluated. Regulating the physico-chemical properties of numerous accessible structures would make clinical diagnosis and therapy safer and more successful. Dendrimeric antigens, nanoallergens, and nanoparticles can mimic carrier proteins, boost specific IgE binding, and improve signal detection in allergy diagnosis. In immunotherapy, several allergenic structures like glycodendrimers, liposomes, polymers, and nanoparticles have been used as adjuvants, protectors, or depots for allergens. Nanotechnology has the potential to substantially improve both the diagnosis and treatment of allergies.

Over 20 years of intensified research in the field of stem cells brought about unprecedented possibilities in treating heart diseases. The investigators were initially fascinated by the idea of regenerating the lost myocardium and replacing it with new functional cardiomyocytes, but this was extremely challenging. However, the multifactorial effects of stem cell-based therapies beyond mere cardiomyocyte generation, caused by paracrine signaling, would open up new possibilities in treating cardiovascular diseases. To date, there is a strong body of evidence that the anti-inflammatory, anti-apoptotic, and immunomodulatory effects of stem cell therapy may alleviate atherosclerosis progression. In the present review, our objective is to provide a brief overview of the stem cell-based therapeutic options. We aim to delineate the pathophysiological mechanisms of their beneficial effects in cardiovascular diseases especially in coronary artery disease and to highlight some conclusions from important clinical studies in the field of regenerative medicine in cardiovascular diseases and how we could further move onwards.

Pharmacologic therapies remain the treatment of choice for patients with essential hypertension, as endorsed by international guidelines. However, several cases warrant additional modalities, such as invasive antihypertensive therapeutics. The major target of these interventions is the modulation of the sympathetic nervous system, which is a common pathophysiologic mechanism in essential hypertension. In this narrative review, we elaborate on the role of invasive antihypertensive treatments with a focus on renal denervation, stressing their potential as well as the drawbacks that prevent their widespread implementation in everyday clinical practice. In the field of renal denervation, several trials have shown significant and sustained reductions in the level of office and ambulatory blood pressure, regardless of the type of energy that was used (radiofrequency or ultrasound). Critically, renal denervation is considered a safe intervention, as evidenced by follow-up data from large clinical trials. Baroreflex activation therapy may result in enhanced parasympathetic nervous system activation, thus lowering blood pressure levels. Along the same lines, carotid body ablation could also produce a significant antihypertensive effect, which has not been tested in appropriately designed randomized trials. Moreover, cardiac neuromodulation therapy could prove efficacious by altering the duration of the atrioventricular interval in order to regulate the preload of the left ventricle and, therefore, lower blood pressure.

Hydrogels are a three-dimensional (3D) network of hydrophilic polymers. The physical and chemical crosslinking of polymeric chains maintains the structure of the hydrogels even when they are swollen in water. They can be modified with thiol by thiol epoxy, thiol-ene, thiol-disulfide, or thiol-one reactions. Their application as a matrix for protein and drug delivery, cellular immobilization, regenerative medicine, and scaffolds for tissue engineering was initiated in the early 21st century. This review focuses on the ingredients, classification techniques, and applications of hydrogels, types of thiolation by different thiol-reducing agents, along with their mechanisms. In this study, different applications for polymers used in thiolated hydrogels, including dextran, gelatin, polyethylene glycol (PEG), cyclodextrins, chitosan, hyaluronic acid, alginate, poloxamer, polygalacturonic acid, pectin, carrageenan gum, arabinoxylan, carboxymethyl cellulose (CMC), gellan gum, and polyvinyl alcohol (PVA) are reviewed.

Inflammation is a well-described factor in the pathophysiology of type 2 diabetes mellitus (DM), which has been a suspect in the alteration of correlations between CRP and leptin in patients with type 2 DM. AIM: This study aimed to show the effect of vitamin C as an antioxidant on the correlation of the serum levels of C-reactive protein (CRP) and leptin in patients with type 2 DM. METHODS: We randomly recruited 70 patients with longstanding T2DM and assigned them into two groups; one received 500 mg/day of vitamin C, and the other received a placebo for eight weeks. Both groups were matched regarding baseline characteristics such as age, gender, weight, and diabetic medications. RESULTS: Out of 70 individuals, 57 participants were left in the study. After eight weeks of follow-up, leptin level was significantly increased in the Vitamin C group (MD=3.48 change=24%, p-value=0.001) but did not change in the placebo group. Other markers such as Fasting plasma glucose, HbA1c, Creatinine, uric acid, Urea, cholesterol, HDL, LDL, TG, AST, ALT, insulin, and CRP did not significantly change in both groups (p value>0.05). The significant changes in the leptin level among the vitamin C group also remained after controlling for age, BMI, Blood pressure (BP), Triglyceride (TG), and cholesterol. Also, the correlation between serum CRP and leptin became significant in the vitamin C group after eight weeks of follow-up but not in the placebo group. (rs =0.730, p<0.001 vs rs =0.286, p-value=0.266 in placebo group). CONCLUSION: This study shows vitamin C can restore CRP-leptin correlation in patients with type 2 diabetes and increase serum leptin levels. More studies are needed to clarify the mechanism of this restoration.

INTRODUCTION: The present study evaluates expression by activated CD4+ T helper1 (Th1) and T helper 2 (Th2) T lymphocytes of pro-inflammatory cytokines and cytoprotective heat shock proteins (HSPs) in peripheral blood of atopic dermatitis (AD) patients. METHODS: This research represents preliminary work by the authors to identify correlates between critical immune parameters with the potential to serve as guidelines for the development of pharmacological strategies for altering these factors to promote the restoration of healthy immune profiles in persons afflicted with major atopic diseases. The major experimental strategy used in this research assessed immune activation by peripheral blood mononuclear cells (PBMC) from 21 AD patients and 12 age- and gender-matched healthy control subjects cultured with phorbol myristate acetate (PMA) and ionomycin (PMA/I), which are mutagenic immune activators, to induce expression of pro-inflammatory biomarkers in CD4+ T cells differentiated to express Th1 or Th2 cytokines and heme oxygenase-1 (HO-1) intracellularly (i). Evaluations were performed using an FC500 Beckman-Coulter flow cytometer. Elevated CD4+ T cell expression of cytokines, interleukin-4 (iIL-4), interleukin- 5 (iIL-5), interleukin-10 (iIL-10), interferon-gamma (iIFN-g), tumor necrosis factor-alpha (iTNF-α), were observed. RESULTS: Additionally, the heat shock proteins (HSP) iHO-1 and iHSP-70 were evaluated in cells from the blood of AD patients versus the control subjects. The present study demonstrated an elevated expression of both Th1 and Th2-associated cytokines in CD4+ T cells of AD patients, with a significant direct correlation between Th1 and Th2 cell populations, thus yielding insight into the immune features of the AD-associated systemic inflammatory profile. CONCLUSION: Finally, the observed increased iHO-1 and iHSP-70 expressions likely represent adaptive physiologic countermeasures to AD-associated inflammatory tissue damage, suggesting that HSP inducers are promising candidates for the management of atopic disorders.

Infected wounds that do not heal are a worldwide problem that is worsening, with more people dying and more money being spent on care. For any disease to be managed effectively, its root cause must be addressed. Effective wound care becomes a bigger problem when various traditional wound healing methods and products may not only fail to promote good healing. Still, it may also hinder the healing process, causing wounds to stay open longer. Progress in tissue regeneration has led to developing three-dimensional scaffolds (3D) or constructs that can be leveraged to facilitate cell growth and regeneration while preventing infection and accelerating wound healing. Tissue regeneration uses natural and fabricated biomaterials that encourage the growth of tissues or organs. Even though the clinical need is urgent, the demand for polymer-based therapeutic techniques for skin tissue abnormalities has grown quickly. Hydrogel scaffolds have become one of the most imperative 3D cross-linked scaffolds for tissue regeneration because they can hold water perfectly and are porous, biocompatible, biodegradable, and biomimetic. For damaged organs or tissues to heal well, the porosity topography of the natural extracellular matrix (ECM) should be imitated. This review details the scaffolds that heal wounds and helps skin tissue to develop. After a brief overview of the bioactive and drug-loaded polymeric hydrogels, the discussion moves on to how the scaffolds are made and what they are made of. It highlights the present uses of in vitro and in-vivo employed biomimetic scaffolds. The prospects of how well bioactive-loaded hydrogels heal wounds and how nanotechnology assists in healing and regeneration have been discussed.

INTRODUCTION: Critical issues in the therapeutic management of cervical cancer (CC) include therapy resistance and treatment failure. The development of therapy resistance is a multifaceted, progressive process, including genetic and epigenetic abnormalities. The present study aimed to identify genes that may contribute to therapy resistance in CC. MATERIALS AND METHODS: We have created an extensive list of the genes in cancer that are therapy-resistant using a text-mining approach. The list was compared with the TCGA-CESC dataset to identify the differentially expressed therapy resistance genes (DETRGs) in CC. We used online resources (UALCAN, DNMIVD, cBioPortal, HCMDB, OncoDB, ShinyGO, HPA, KM Plotter, TIMER, and DGIdb) to determine the potential association between methylation and expression of therapy resistance genes with the prognosis and clinical outcomes in CC. RESULTS: The systematic analysis identified 71 out of 91 DETRGs showed aberrant DNA methylation. The overlapping analysis identified 25 genes to show an inverse correlation between methylation and expression. Further, differential expression or methylation could be helpful in CC staging, HPV association, prediction of metastasis and prognosis. The study identified seven driver genes in CC. The PPIN identifies ten hub genes (HGs) associated with CC staging, cancer hallmarks, and prognosis to affect long-term survival. CONCLUSION: Our thorough investigation uncovered several novel genes and pathways that might contribute to therapy resistance in CC. The genes identified in our study may serve as a biomarker, prognostic indicator, and therapeutic target in CC.

The treatment options for hepatitis C have undergone noteworthy advancements since direct-acting antivirals (DAAs) were introduced. The selection of a DAA therapy depends on the patient's genotype, treatment history, concomitant comorbidities, and concurrent medications. Pharmacists have a pivotal role in providing clarification and recommendations in selecting appropriate, individualized DAAs for patients. This commentary aims to (1) provide an overview of DAAs on the market for hepatitis C, and (2) describe the implication for the care of patients with hepatitis C in a community pharmacy. Community pharmacists can establish a workflow to recommend appropriate DAA therapy, identify drug interactions, and improve medication adherence and compliance with lab appointments.