Alzheimer's disease (AD) is one of the most complicated neurodegenerative diseases causing dementia in human beings. Aside from that incidence of AD is increasing also its treatment is very complicated. There are several known hypotheses regarding the pathology of Alzheimer's disease, including the Amyloid beta hypothesis, Tau hypothesis, inflammation hypothesis, and cholinergic hypothesis, which are investigated in different researches to completely elucidate the pathology of AD. Aside from these some new mechanisms such as immune, endocrine, and vagus pathways, as well as bacteria metabolite secretions are being explained as other causes that are somehow related to AD pathogenesis. There is still no definite treatment for Alzheimer's disease that can completely cure and eradicate AD. Garlic (Allium sativum) is a traditional herb used as a spice in different cultures and due to the organosulfur compounds like allicin it possesses highly anti-oxidant properties and the benefits of garlic in cardiovascular diseases like hypertension and atherosclerosis is examined and reviewed, although its beneficiary effects in neurodegenerative diseases such as AD is not completely understood. In this review, we discuss the effects of garlic based on its components such as allicin, S-allyl cysteine on Alzheimer's disease and the mechanisms that garlic components can be beneficiary for AD patients, including its effects amyloid beta, oxidative stress, tau protein, gene expression, and cholinesterase enzymes. Based on the literature review we have done, garlic has revealed beneficiary effects on Alzheimer's disease, especially in animal studies; however, more studies should be done on human populations to find the exact mechanism of garlic effects on AD patients.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a syndrome characterized by marked heterogeneity in comorbidities and etiopathology substrates, leading to a diverse range of clinical manifestations and courses. Treatment options have been extremely limited and up to this day, there are virtually no pharmaceutical agents proven to reduce mortality in these patients. OBJECTIVE: The primary objective of this narrative review is to critically summarize existing evidence regarding the use of Angiotensin Receptor-Neprilysin Inhibitor (ARNI), spironolactone, pirfenidone and empagliflozin in HFpEF. METHODS: Medline (via PubMed) and Scopus were searched - from inception up to May 2022- using adequately selected keywords. Additional hand-search was also performed using the references of the articles identified as relevant (snowball strategy). RESULTS: Angiotensin Receptor-Neprilysin Inhibitor (ARNI) and spironolactone, despite being very successful in HFrEF, did not do well in clinical trials of HFpEF, although there appear to be certain subsets of patients who may derive benefit. Data regarding pirfenidone are limited and come from small trials; as a result, it would be premature to draw firm conclusions, although it seems improbable that this agent will ever become a mainstay in the general population of HPpEF patients, while there may be a niche for the drug in individuals with comorbidities associated with an intense fibrotic activity. Finally, empagliflozin, largely welcomed as the first agent to have a "positive" randomized clinical trial in HFpEF, does not seem to evade the general pattern of reduced hospitalizations for HF with no substantial effect on mortality, seen in ARNI and spironolactone HFpEF trials. CONCLUSION: Recent research in drug treatment for HFpEF has resulted in an overall mixed picture, with trials showing potential benefits from certain classes of drugs, such as sodium-glucose co-transporter 2 inhibitors, and no benefit from other drugs, which have shown to be effective in patient with reduced ejection fraction. However, small steps may be the way to go in HFpEF, and success is sometimes just a series of small victories.

Exercise-based cardiac rehabilitation (EBCR) is a treatment modality for patients with heart failure (HF) that has withstood the test of time. It has continued to show benefits even in the current era of pharmacotherapeutics for HF. Participation in a multidisciplinary comprehensive EBCR programme reduces mortality and morbidity, has a multitude of physiological benefits, and improves cardiovascular risk factor control and quality of life. Despite this, historical barriers to enrolment and uptake remain. Strategies to overcome these, as well as alternative delivery methods of EBCR in HF patients, are emerging and include telerehabilitation, focus on special groups and emphasis on behavioural change. This review provides oversight on the modalities of exercise training in HF as well as their benefits and gives an overview of barriers to the utilisation of EBCR along with future progress in the field.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a relatively novel drug class that most cardiologists are becoming familiar with. By contrasting glucose reabsorption in the proximal convoluted tubule of the nephron, SGLT2 inhibition results in glycosuria with improved glycemic control. Although originally introduced as anti-diabetic medications, the cardiovascular effects of SGLT2i have progressively emerged, leading them to become one of the four pillars for the treatment of heart failure with reduced ejection fraction (HFrEF) according to the 2021 guidelines from the European Society of Cardiology. Also, two recent randomized trials have demonstrated SGLT2i as the first compound with proven prognostic impact in heart failure with preserved ejection fraction (HFpEF), setting a milestone in the treatment for this condition. While the exact pathogenic mechanisms mediating the substantial reduction in cardiovascular death and heart failure (HF) hospitalizations are still controversial, there is growing clinical evidence on the efficacy and safety of SGLT2i in various subsets of patients with HF. As known, heart failure is a complex and heterogeneous clinical syndrome with a magnitude of phenotypes and a variety of underlying hemodynamic and physiological aspects which cannot be fully incorporated into the traditional left ventricular ejection fraction based classification adopted in clinical trials. The aim of this review is to provide an overview of the cardiovascular benefits and indications of SGLT2i across different HF patterns and to highlight current gaps in knowledge that should be addressed by future research.

AIMS: A network pharmacological analysis combined with experimental validation was used to investigate the neuroprotective mechanism of the natural product Tetramethylpyrazine(TMP). BACKGROUND: Protecting neurons is critical for acute ischemic stroke treatment. Tetramethylpyrazine is a bioactive component extracted from Chuanxiong. The neuroprotective potential of TMP has been reported, but a systematic analysis of its mechanism has not been performed. OBJECTIVE: Based on the hints of network pharmacology and bioinformatics analysis, the mechanism by which TMP alleviates oxygen-glucose deprivation-induced neuronal damage through inhibition of the HIF-1α/BNIP3 pathway was verified. METHOD: In this study, we initially used network pharmacology and bioinformatics analyses to elucidate the mechanisms involved in TMP's predictive targets on a system level. The HIF-1α/BNIP3 pathway mediating the cellular response to hypoxia and apoptosis was considered worthy of focus in the bioinformatic analysis. An oxygen-glucose deprivation (OGD)-induced PC12 cell injury model was established for functional and mechanical validation. Cell viability, lactate dehydrogenase leakage, intracellular reactive oxygen species, percentage of apoptotic cells, and Caspase-3 activity were determined to assess the TMP's protective effects. Transfection with siRNA/HIF-1α or pcDNA/HIF-1α plasmids to silence or overexpress hypoxia-inducible factor 1α(HIF-1α). The role of HIF-1α in OGD-injured cells was observed first. After that, TMP's regulation of the HIF-1α/BNIP3 pathway was investigated. The pcDNA3.1/HIF-1α-positive plasmids were applied in rescue experiments. RESULT: The results showed that TMP dose-dependently attenuated OGD-induced cell injury. The expression levels of HIF-1α, BNIP3, and the Bax/Bcl-2 increased significantly with increasing OGD duration. Overexpression of HIF-1α decreased cell viability, increased BNIP3 expression, and Bax/Bcl-2 ratio; siRNA-HIF-1α showed the opposite effect. TMP treatment suppressed HIF-1α, BNIP3 expression, and the Bax/Bcl-2 ratio and was reversed by HIF-1α overexpression. CONCLUSION: Our study shows that TMP protects OGD-damaged PC12 cells by inhibiting the HIF-1α/BNIP3 pathway, which provides new insights into the mechanism of TMP and its neuroprotective potential.

OBJECTIVE: We aimed to evaluate the effectiveness of topical tranexamic acid (TXA) versus topical vasoconstrictors in the management of epistaxis via a systematic review and meta-analysis. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were followed for the meta-analysis. We systematically searched Embase, Web of Science, Cochrane Library, CNKI, and PubMed for randomized controlled trials (from inception to August 2022; no language restrictions), comparing the effect of topical TXA and topical vasoconstrictors on the treatment of epistaxis. The Q test was used to evaluate heterogeneity, and funnel plots were utilized to identify bias. For the meta-analysis, the fixed-effects model was employed, and the t-test was utilized to determine significance. RESULTS: Of 1012 identified studies, 5 were found to be eligible for our analysis. In total, 598 patients were included; 297 of them received TXA and 301 received vasoconstrictors. Hemostasis was more likely to be achieved at the first re-assessment in patients treated with TXA. Subgroup analysis indicated patients treated with TXA to have less likelihood of bleeding recurrence, compared to patients treated with vasoconstrictors. The detected time interval of rebleeding was 10 min, between 24h to 72h, and after 7 days, respectively, and the differences were significant between the two groups of patients treated with TXA and vasoconstrictors. CONCLUSION: Topical TXA was associated with better post-treatment hemorrhagic arrest rates compared to topical vasoconstrictors in the management of epistaxis.

Bioactive peptides are specific protein fragments that prove health-promoting potential for humans. The bioactivities include antimicrobial, antioxidant, anticancer, immunomodulatory activities, etc. Hence, bioactive peptides' production technology and processes have attracted excessive attention, especially concerning peptides' synthesis, separation, identification, and functionality. This review summarizes the relevant investigations from the above four aspects. Among the production technology of bioactive peptides, biosynthesis, chemosynthesis, technology for separation and purification, and the interactions responsible for peptide-based nanostructures are emphasized. Here, the biosynthesis of peptides includes enzymatic hydrolysis, microbial fermentation, and recombinant DNA technology, and chemosynthesis consists of solution-phase peptide synthesis and solid-phase peptide synthesis (SPPS). The commonly used enzymes in enzymatic hydrolysis are investigated, including pepsin, trypsin, and alcalase. The commonly used microorganisms, typical processes, protein sources, and advantages of microbial fermentation are analyzed. Membrane separation (including ultrafiltration and nanofiltration), chromatography technology (including ion-exchange chromatography, gel filtration chromatography, affinity chromatography, and reverse-phase high-performance liquid chromatography (RP-HPLC)), and electrophoresis technology are detailed for the purification technology. Mass spectrometry (MS), its combination with the high-performance separation method, and nuclear magnetic resonance (NMR) are elucidated for the identification technology. The non-covalent interactions responsible for peptide-based nanostructures involve electrostatic force, hydrogen bonds, π-π stacking, hydrophobic interaction, and van der Waals force. Afterward, we detail the peptides' antihypertensive, antithrombotic, anticancer, antimicrobial, antioxidant, and immunomodulatory activities. The activity analysis mainly involves peptides' sources, structural features, mechanisms of action, and influencing factors. Based on the production and functionality elucidation, potential challenges for peptide application in biomedicine are given. The challenge is analyzed from the aspects of purification and identification technologies and influencing factors of peptides' bioactivities. Our work will elaborate on advances in the production technology of peptides and their bioactivities, which could promote and expand their industrial applications.

AIM: We aimed to design RGD-anchored liposomes encapsulating an antipyroptosis drug that could efficiently target macrophages and relieve the rate of cytokine release syndrome, providing a new strategy for sepsis treatment, especially sepsis-induced acute renal injury. BACKGROUND: Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by host response disorders due to infection. Sepsis has a high incidence and remains one of the leading causes of death worldwide. OBJECTIVE: Macrophage-mediated pyroptosis plays an important role in the occurrence and development of cytokine release syndrome and organ injury caused by sepsis. Curcumin can inhibit inflammasome assembly and slow the progression of pyroptosis by scavenging intracellular reactive oxygen species, but it has poor water solubility and low bioavailability. The emergence of drug-delivery nanosystems has overcome this problem, but there is still a lack of research on how to accurately deliver antipyroptotic drugs to innate immune cells and subsequently hinder pyroptosis. METHOD: We constructed a curcumin-loaded RGD-modified liposome (RGD-lipo/Cur) and demonstrated that RGD-lipo/Cur could effectively target macrophages. RESULT: In vitro, RGD-lipo/Cur reduced the upregulation of caspase-1, caspase-3, NLRP3, IL-1β and GSDMD, inhibiting pyroptosis, reducing oxidative stress, and attenuating the proinflammatory cytokine cascade. CONCLUSION: RGD-lipo/Cur was considered to have great potential for sepsis treatment.