Overview of the Justicia Genus: Insights into Its Chemical Diversity and Biological Potential.

The genus Justicia has more than 600 species distributed in both hemispheres, in the tropics and temperate regions, and it is used in the treatment of numerous pathologies. This study presents a review of the biological activities of plant extracts and isolated chemical constituents of Justicia (ACANTHACEAE), identified in the period from May 2011 to August 2022. We analyzed over 176 articles with various biological activities and chemical compound descriptions present in the 29 species of Justicia. These have a variety of applications, such as antioxidant and antimicrobial, with alkaloids and flavonoids (e.g., naringenin) the most frequently identified secondary metabolites. The most observed species were Justicia gendarussa Burm., Justicia procumbens L., Justicia adhatoda L., Justicia spicigera Schltdl, and Justicia pectoralis Jacq. The frontier molecular orbitals carried out using density functional theory (M062X and basis set 6-311++G(d,p) indicate reactive sites for naringenin compound and a chemical reaction on phytomedicine activity. The energy gap (206.99 kcal/mol) and dimer solid state packing point to chemical stability. Due to the wide variety of pharmacological uses of these species, this review points toward the development of new phytomedicines.

Pharmacological evaluation of antinociceptive and anti-inflammatory activities of LQFM202: a new piperazine derivative.

Advances have been made in the search for new multi-target modulators to control pain and inflammation. Therefore, compound 3,5-di-tert-butyl-4-hydroxyphenyl)(4-methylpiperazin-1-yl)methanone (LQFM202) was synthesised and evaluated. First, in vitro assays were performed for COX-1, COX-2, and 5-LOX enzymes. Subsequently, adult female Swiss albino mice treated orally with LQFM202 at doses of 25-200 mg/kg were subjected to acetic acid-induced writhing, formalin-induced pain, carrageenan-induced hyperalgesia, carrageenan- or zymosan-induced paw oedema, or pleurisy. LQFM202 inhibited COX-1, COX-2, and LOX-5 (IC50 = 3499 µM, 1565 µM, and 1343 µM, respectively). In acute animal models, LQFM202 (50, 100, or 200 mg/kg) decreased the amount of abdominal writhing (29%, 52% and 48%, respectively). Pain in the second phase of the formalin test was reduced by 46% with intermediate dose. LQFM202 (100 mg/kg) reduced the difference in nociceptive threshold in all 4 h evaluated (46%, 37%, 30%, and 26%, respectively). LQFM202 (50 mg/kg) decreased the carrageenan-oedema from the second hour (27%, 31% and 25%, respectively); however, LQFM202 (100 mg/kg) decreased the carrageenan-oedema in all hours evaluated (35%, 42%, 48% and 50%, respectively). When using zymosan, LQFM202 (50 mg/kg) decreased the oedema in all hours evaluated (33%, 32%, 31% and 20%, respectively). In the carrageenan-pleurisy test, LQFM202 (50 mg/kg) reduced significantly the number of polymorphonuclear cells (34%), the myeloperoxidase activity (53%), TNF-α levels (47%), and IL-1ß levels (58.8%). When using zymosan, LQFM202 (50 mg/kg) reduced the number of polymorphonuclear and mononuclear cells (54% and 79%, respectively); and the myeloperoxidase activity (46%). These results suggest antinociceptive and anti-inflammatory effects of LQFM202.

Anti-inflammatory and antinociceptive effects, and safety toxicological profile of a new paracetamol analog, LQFM291.

In the scope of a research program with the goal of developing treatments for inflammatory diseases, the pharmacological evaluation of LQFM291, designed by molecular hybridization from butylated hydroxytoluene and paracetamol, was described. The antioxidant profile of LQFM291 was evaluated by electrochemical measurement. Also, acute or repeated treatments with equimolar doses to paracetamol were used to evaluate the antinociceptive and/or anti-inflammatory activities of LQFM291 in animal models. The toxicologic potential of LQFM291 was also evaluated and compared to paracetamol through biochemical and histopathological analysis after the repeated treatment schedule. As a result of the acute treatment, paracetamol showed a similar antinociceptive effect in formalin test compared to LQFM291. Whereas, after the repeated treatment, when carrageenan-induced hyperalgesia and edema tests were performed, paracetamol showed a delayed antinociceptive and anti-inflammatory effect compared to LQFM291. Furthermore, as other advantages the LQFM291 showed a high redox capacity, a gastroprotective activity and a safety pharmacological profile without any liver or kidney damage. These effects can be related to the prevention of oxidative stress by reduction of protein and lipid peroxidation in gastric tissue, maintenance of glutathione levels in hepatic homogenate, and a systemic reduction of pro-inflammatory cytokine levels, which may characterize the LQFM291 as a more viable and effective alternative to relief pain and inflammatory signs in patients with chronic disorders.

Involvement of the Benzodiazepine Site in the Anticonvulsant Activity of Tapinanthus globiferus against Pentylenetetrazole-induced Seizures in Mice.

Tapinanthus globiferus is often referred to as an all-purpose herb for the treatment of stroke and epilepsy. The present study investigates the anticonvulsant effect of methanolic leaf extract, active fractions, and lupeol (isolate) of Tapinanthus globiferus in mice as well as the underlying mechanisms. Following phytochemical studies of T. globiferus, preliminary assays were performed to evaluate MLE-induced toxic effect and behavioral changes. The pentylenetetrazol (70 mg/kg, i. p.)-induced seizure was evaluated in mice that were pretreated orally with vehicle 10 mL/kg, MLE (4, 20, or 100 mg/kg), fractions (F1 to F6), lupeol 10 mg/kg or diazepam (3 mg/kg). Methanolic leaf extract preserved neuron viability as well as the relative organ weight, and hematological and biochemical parameters. The behavioral endpoints, neuromuscular coordination, and sensory response parameters revealed a dose-dependent effect of methanolic leaf extract. This extract, active fractions, lupeol, and diazepam potentiated the hypno-sedative effect of the barbiturate and attenuated PTZ-induced acute seizure. This antiseizure effect was completely reversed by flumazenil 2 mg/kg (benzodiazepine site antagonist). Altogether, the benzodiazepine site-mediated anticonvulsant effects of methanolic leaf extract, active fractions, and lupeol corroborate traditional application of T. globiferus against epilepsy.

Pharmacological and toxicological evaluations of the new pyrazole compound (LQFM-021) as potential analgesic and anti-inflammatory agents.

Chronic inflammation is a world health problem. There is a need to develop new anti-inflammatory and analgesic drugs with improved activity and reduced side effects. In this context, the aim of this study was to evaluate the antinociceptive and anti-inflammatory effects of the pyrazole compound LQFM-021 after acute and sub-chronic administration in rats submitted to a CFA-induced chronic arthritis model, as well as compare the toxicity of this compound to that of dipyrone, given throughout 7 days. Firstly, we observed that acute oral administration of the higher dose (130 µmol/kg) of LQFM-021 reduced paw lifting time (PET) and edema formation. These effects disappeared on the following day, requiring another dose to maintain the effects. This dose also promoted reduction of the polymorphonuclear recruitment in the synovial fluid. In another experiment, both treatments with LQFM-021, 65 µmol/kg twice a day and 130 µmol/kg once a day, produced a progressive and permanent reduction of the PET and edema, also reducing polymorphonuclear recruitment. However, the single treatment with 130 µmol/kg was more effective than the double treatment with 65 µmol/kg. LQFM-021 did not produce toxicity signs. However, dipyrone (130 µmol/kg once a day) promoted erosion of the epithelial cells and decreased mucus in the gastric mucosa. These data indicate that LQFM-021 produced antinociceptive and anti-inflammatory effects in CFA-induced arthritis in rats. These effects occurred in the absence of apparent toxic effects, indicating that the pyrazole compound LQFM-021 may be considered a good prototype for development of new analgesic/anti-inflammatory drug.

Evaluation of Gastroprotective Activity of the Methanolic Extract of Justicia pectoralis Jacq. (Acanthaceae).

INTRODUCTION: Justicia pectoralis Jacq. is traditionally applied in folk medicine in Brazil and in several Latin American countries. The leaves are used in tea form, especially in the treatment of respiratory disorders, acting as an expectorant. It also has activity in gastrointestinal disorders, and it is anti-inflammatory, antioxidant, sedative, and estrogenic, among others. AIMS: To investigate the gastroprotective activity of the methanol extract of the leaves of Justicia pectoralis Jacq. (MEJP) in different experimental models of gastric ulcers. MATERIALS AND METHODS: The adult leaves of Justicia pectoralis Jacq. were collected and cultivated in beds, with an approximate spacing of 40 × 40 cm, organic fertilization, irrigation with potable water and without shelter from light. The MEJP was prepared from the dried and pulverized leaves and concentrated under reduced pressure in a rotary evaporator. For the experimental model of gastric ulcer, Swiss male albino mice were used. The inputs used in the experiment were MEJP at three different concentrations (250, 500 and 1000 mg/kg p.o.), cimetidine (50 mg/kg p.o.), indomethacin (50 mg/kg s.c.) and vehicle (10 mL/kg p.o.). RESULTS: MEJP (250, 500 and 1000 mg/kg p.o.) demonstrated gastroprotective activity, with levels of protection of 45.65%, 44.80% and 40.22%, respectively, compared to the control (vehicle). Compared with cimetidine (48.29%), MEJP showed similar gastroprotective activity. CONCLUSIONS: This study demonstrated the gastroprotective activity of MEJP and contributes to validate the traditional use the species for gastric disorders and provides a pharmacological basis for its clinical potential.

Heteroaromatic salvinorin A analogue (P-3 l) elicits antinociceptive and anxiolytic-like effects.

Previous studies have attributed the prominent analgesic, hallucinogenic, sedative, and anxiolytic properties of Salvia divinorum to Salvinorin A. However, the overall pharmacological profile of this isolate limits its clinical applications. To address these limitations, our study evaluates the C(22)-fused-heteroaromatic analogue of salvinorin A [2-O-salvinorin B benzofuran-2-carboxylate] (P-3l) in mice nociception and anxiety models while assessing possible mechanism of action. In comparison with the control group, orally administered P-3l (1, 3, 10, and 30 mg/kg) attenuates acetic acid-induced abdominal writhing, formalin-induced hind paw licking, the thermal reaction to the hotplate, and/or aversive response in the elevated plus-maze, open field, and light-dark box; and potentiates the effect of morphine and diazepam at sub-effective doses (1.25 and 0.25 mg/kg, respectively) without eliciting significant alterations in relative organ weight, or haematological or biochemical parameters. The in vivo blockade of P-3 l effects by naloxone (non-selective opioid receptor antagonist), naloxonazine (antagonist of specific subtypes mu1 of µ-OR), and nor-binaltorphimine (selective ĸ-OR antagonist) supports initial results from binding assays and the interpretations made possible from computational modeling of the interactions of P-3 l with the opioid receptor subtypes. In addition to the opioidergic mechanism, the blockade of the P-3 l effect by flumazenil suggests benzodiazepine binding site involvement in its biological activities. These results support P-3 l potentially possessing clinical utility and substantiate the need for additional pharmacological characterization.

Cardiovascular Risk Prediction by the American Diabetes Association Risk-Assessment Tool and Novel and Traditional Cardiovascular Risk Factors in Young Adults With Type 1 Diabetes.

INTRODUCTION: Cardiovascular disease is an important cause of morbidity and mortality in individuals with type 1 diabetes (T1D). The American Diabetes Association (ADA) has the ADA risk-assessment tool for cardiovascular risk (CVR) prediction in individuals with T1D. This study aims to evaluate the prevalence of novel and traditional cardiovascular risk factors (CVRF) and the CVR by the ADA risk-assessment tool: 10-year risk for diabetes complications in young adults with T1D. METHODS: Cross-sectional observational study of T1D individuals aged 18-40 years and T1D duration ≥1 year. The ADA risk-assessment tool was applied to predict CVR. RESULTS: 75 individuals, 61.3% male, with a median age of 30 (26.0-36.0) and 13.0 (6.0-20.0) years of T1D duration. Hypertension was found in 16% of individuals and dyslipidemia in 75.0%. 21.3% were active smokers, 30.7% sedentary, and 42.7% were at least overweight. Most individuals had a 10-year risk <1% for all complications except myocardial infarction (MI). In individuals who were outside the honeymoon period (T1D duration ≥ 5 years), most had a 10-year risk <1% for all complications except MI and amputation. Non-traditional CVRF homocysteine, apolipoprotein B, apolipoprotein B/apolipoprotein A1 ratio, magnesium, and vitamin D correlated with the ADA risk-assessment tool. 10-year risk for MI ≥1% was significantly more frequent in men. CONCLUSION: To our knowledge, this is the first study to apply the ADA risk-assessment tool: 10-year risk for diabetes complications in T1D. Young adults with T1D have a worrying prevalence of CVRF and show suboptimal control. Most individuals with T1D duration ≥1 year have an estimated 10-year risk <1% for all complications, except for MI.

Heterocyclic Compounds: Pharmacology of Pyrazole Analogs From Rational Structural Considerations.

Low quality of life and life-threatening conditions often demand pharmacological screening of lead compounds. A spectrum of pharmacological activities has been attributed to pyrazole analogs. The substitution, replacement, or removal of functional groups on a pyrazole ring appears consistent with diverse molecular interactions, efficacy, and potency of these analogs. This mini-review explores cytotoxic, cytoprotective, antinociceptive, anti-inflammatory, and antidepressant activities of some pyrazole analogs to advance structure-related pharmacological profiles and rational design of new analogs. Numerous interactions of these derivatives at their targets could impact future research considerations and prospects while offering opportunities for optimizing therapeutic activity with fewer adverse effects.

Practical band interpolation with a modified tight-binding method.

We present a scheme that interpolates the energy bands of a crystal with a modified tight-binding Hamiltonian. We start from a pseudopotential plane-wave calculation of the eigenvalues in a three-dimensional coarse uniform grid of k-points in the Brillouin zone and from the evaluation of the single particle Hamiltonian and overlap matrix elements for a small localised basis set of atomic orbitals in the same k-point grid. A simple matrix manipulation procedure that replaces the eigenvalues obtained from the atomic orbital method by the eigenvalues of the plane-wave method generates the modified tight-binding Hamiltonian on the coarse grid. A subsequent three-dimensional Fourier interpolation of the modified tight-binding Hamiltonian and overlap matrices leads to a fast, yet accurate, determination of interpolated Hamiltonians and overlap matrices at an arbitrary k-point, or in a denser grid of k-points. We present examples of the application of the scheme to density functional calculations of germanium, graphite, graphene, copper and a SiGe superlattice.

Spontaneous coronary artery dissection: "To stent or not to stent, that is the question". / Disseção coronária espontânea ­ To stent or not to stent that is the question.

Spontaneous coronary artery dissection is a rare cause of acute coronary syndrome that typically occurs in relatively young patients without classical cardiovascular risk factors for coronary artery disease. The etiology appears to be multifactorial and optimal management is not clearly established, so the treatment strategy is often selected based on clinical presentation and coronary anatomy. We present two cases of spontaneous coronary artery dissection with different initial approaches, highlighting the importance of a case-by-case assessment.

Alteplase for Massive Pulmonary Embolism after Complicated Pericardiocentesis.

BACKGROUND: The occurrence of a high-risk pulmonary embolism (PE) within 48 hours of a complicated pericardiocentesis to remove a haemorrhagic pericardial effusion, is an uncommon clinical challenge. CASE SUMMARY: The authors report the case of a 75-year-old woman who presented with signs of imminent cardiac tamponade due to recurring idiopathic pericardial effusion. The patient underwent pericardiocentesis that was complicated by the loss of 1.5 litres of blood. Within 48 hours, the patient had collapsed with clear signs of obstructive shock. This was a life-threating situation so alteplase was administered after cardiac tamponade and hypertensive pneumothorax had been excluded. CT chest angiography later confirmed bilateral PE. The patient achieved haemodynamic stability less than an hour after receiving the alteplase. However, due to the high risk of bleeding, the medical team suspended the thrombolysis protocol and switched to unfractionated heparin within the hour. The cause of the PE was not identified despite extensive study, but after 1 year of follow-up the patient remained asymptomatic. DISCUSSION: Despite the presence of a contraindication, the use of thrombolytic therapy in obstructive shock after exclusion of hypertensive pneumothorax can be life-saving, and low-dose thrombolytic therapy may be a valid option in such cases. LEARNING POINTS: A quick and systematic approach to a collapsed patient with signs of shock is mandatory; understanding the type of shock may help narrow the differential diagnosis and help in therapeutic decisions.After exclusion of cardiac tamponade and hypertensive pneumothorax, life-saving thrombolytic therapy can be administered in obstructive shock due to probable massive pulmonary embolism.Contraindications for thrombolytic therapy originated as exclusion criteria for clinical trials but should not prevent the use of this therapy in life-threatening situations.

Fractional Flow Reserve-Guided Strategy in Acute Coronary Syndrome. A Systematic Review and Meta-Analysis.

BACKGROUND: There are limited data on the prognosis of deferral of lesion treatment in patients with acute coronary syndrome (ACS) based on fractional flow reserve (FFR). OBJECTIVES: To provide a systematic review of the current evidence on the prognosis of deferred lesions in ACS patients compared with deferred lesions in non-ACS patients, on the basis of FFR. METHODS: We searched Medline, EMBASE, and the Cochrane Library for studies published between January 2000 and September 2017 that compared prognosis of deferred revascularization of lesions on the basis of FFR in ACS patients compared with non-ACS patients. We conducted a pooled relative risk meta-analysis of four primary outcomes: mortality, cardiovascular (CV) mortality, myocardial infarction (MI) and target-vessel revascularization (TVR). RESULTS: We identified 7 studies that included a total of 5,107 patients. A pooled meta-analysis showed no significant difference in mortality (relative risk [RR] = 1.44; 95% CI, 0.9-2.4), CV mortality (RR = 1.29; 95% CI = 0.4-4.3) and TVR (RR = 1.46; 95% CI = 0.9-2.3) after deferral of revascularization based on FFR between ACS and non-ACS patients. Such deferral was associated with significant additional risk of MI (RR = 1.83; 95% CI = 1.4-2.4) in ACS patients. CONCLUSION: The prognostic value of FFR in ACS setting is not as good as in stable patients. The results demonstrate an increased risk of MI but not of mortality, CV mortality, and TVR in ACS patients.

Medical treatment or revascularisation as the best approach for spontaneous coronary artery dissection: A systematic review and meta-analysis.

INTRODUCTION: Patients presenting with spontaneous coronary artery dissection (SCAD) may receive either conservative medical management or a revascularisation strategy. There is still a lack of consensus with respect to the best treatment approach for SCAD. OBJECTIVES: We sought to determine whether outcomes differ between the first-line treatment approaches (conservative versus revascularisation) in patients with SCAD. METHODS: We searched Medline, EMBASE and the Cochrane Library for studies published from January 1990 to November 2016 that compared first-line treatments for patients with SCAD. We conducted a pooled risk ratio meta-analysis for four main outcomes: mortality, myocardial infarction (MI), SCAD recurrence and target vessel revascularisation (TVR). RESULTS: We identified 11 non-randomised studies that included a total of 631 patients. A pooled meta-analysis showed no significant difference between conservative management and revascularisation approaches in mortality (risk difference [RD] = 0.01; 95% confidence interval [CI] = -0.01 to 0.04; I2 = 0%; p = 1), MI (RD = -0.01; 95% CI = -0.04 to 0.03; I2 = 0%; p = 0.5) or SCAD recurrence (RD = -0.01; 95% CI = -0.06 to 0.05; I2 = 0%; p = 0.74). Revascularisation as an initial first-line approach was associated with an estimated additional risk of TVR of 6.3% (RD = 0.06; 95% CI = 0.01-0.11; I2 = 0%; p = 0.96). CONCLUSION: The results demonstrate an increased risk of TVR when revascularisation was used as the initial first-line treatment approach. The treatment decision must be individualised and be based on both clinical and angiographic factors, but conservative therapy should prevail in most cases.

Worsening or 'pseudo-worsening' renal function? The prognostic value of hemoconcentration in patients admitted with acute heart failure.

INTRODUCTION: Renal insufficiency, as evidenced by an increase in creatinine, is associated with higher mortality in patients with acute heart failure (AHF). Conversely, hemoconcentration (HC) in AHF is associated with lower mortality, but can also cause an increase in creatinine. Our aim was to assess the prognosis of HC in patients hospitalized for AHF presenting with or without worsening renal function (WRF). METHODS: A total of 618 consecutive patients admitted for AHF were included. WRF was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria and HC was defined as an elevation of hemoglobin during hospitalization compared to the admission value. Six-month all-cause mortality was analyzed. RESULTS: The patients' mean age was 79±11 years; 58% were women. Mortality at six months was 38% and 49% of patients had WRF. HC occurred in 38.9% of patients with WRF and was associated with improved survival (HR 1.6, 95% CI 1.10-2.34; p=0.02) compared to WRF without HC. HC was associated with better survival in KDIGO stages 1 and 2 (HR 1.8; 95% CI 1.1-2.8; p=0.01). For patients without chronic kidney disease (CKD) with WRF in stages 1 and 2, HC was associated with significantly better survival (HR 2.3; 95% CI 1.2-4.2; p=0.01). CONCLUSION: In patients admitted for AHF without renal failure or CKD, WRF with HC is associated with a better prognosis, similar to that of patients without WRF, and should therefore be reclassified as 'pseudo-WRF'.

Are soccer matches dangerous for patients with heart disease? The HeartAtaque trial - a prospective pilot study. / Jogos de futebol impróprios para cardíacos (HeartAtaque trial) ­ Estudo piloto prospetivo.

INTRODUCTION: Behavioral and emotional factors are triggers of cardiovascular events (CVEs). It is uncertain whether soccer fans, particularly individuals with coronary artery disease (CAD), are at increased risk for CVEs. OBJECTIVES: To assess the effect of watching soccer matches in patients with known CAD on the incidence of CVEs according to the match result. METHODS: We prospectively assessed 82 male soccer fans with a history of acute coronary syndrome during 23 matches of the 2015/2016 season. Each individual was assessed by Holter monitoring on the day of their team's match and on the control day. The primary endpoint was the composite of death, stroke, reinfarction, angina or sustained arrhythmia. Secondary endpoints assessed were episodes of non-sustained supraventricular or ventricular arrhythmia and mean heart rate (HR). RESULTS: Participants' mean age was 61±10 years. Compared with the control day, despite a significant increase in HR (p<0.001) that was independent of the result (p>0.97), the number of CVEs did not differ according to the result (p>0.05). Moreover, the number of non-sustained episodes of supraventricular and ventricular arrhythmia did not differ when stratified according to the match result (p>0.05). CONCLUSIONS: The match result was not associated with a difference in incidence of CVEs in patients with a past history of CAD, with ischemic and arrhythmic substrate, who watched soccer matches on television.

Adherence to antiretroviral therapy and correlation with adverse effects and coinfections in people living with HIV/AIDS in the municipality of Goiás State.

INTRODUCTION: Acquired immunodeficiency syndrome is an advanced stage of a human immunodeficiency virus infection. The antiretroviral therapy aims to improve the life quality of HIV patients and a good adherence is essential for a better prognosis. This study aimed to evaluate the adherence of human immunodeficiency virus/acquired immunodeficiency syndrome patients to antiretroviral therapy recommended by the Brazilian health system in Anápolis/Goiás, and correlate the level of adherence with sociodemographic data and clinical-laboratory variables. METHODS: Adherence to antiretroviral therapy was assessed using the Questionnaire for Evaluation of Adherence to Antiretroviral Therapy. The sociodemographic data were collected using a standardized questionnaire and the clinical-laboratory records were reviewed. RESULTS: Among 220 patients included, 59% (129/220) were men and the average age was 41 years. Infection was acquired primarily through sexual contact (92%, 202/220), and 69% (152/220) of the patients were heterosexual. Approximately 86% (188/220) of the patients had good or strict adherence to antiretroviral therapy. In our study, the use of illicit drugs was associated with low adherence to antiretroviral therapy (p=0.0004), and no significant association was observed between adherence levels and other sociodemographic data (p>0.05). The logistic regression indicated that adverse effects (p=0.0018) and sexual orientation (p=0.0152) were associated with the level of adherence to antiretroviral therapy. Patients with good or strict adherence had higher CD4+T lymphocyte count (p<0.0001) and undetectable viral load (p<0.0001). Patients with low adherence (14%, 32/220) had higher frequency of adverse events (p=0.0009). The frequency of coinfections was 25% (55/220), with syphilis and tuberculosis being the most common coinfections. CONCLUSIONS: Adherence was related to use of illicit drugs, adverse effects, and sexual orientation.

Effect of allantoin on experimentally induced gastric ulcers: Pathways of gastroprotection.

Gastric ulcer affects people worldwide, and its inefficacy and recurrence have fueled the search for new therapeutic strategies. Despite the well-known use of allantoin in medicines and cosmetic products, its effect has not yet been studied with regard to gastric ulcer. Hence, the aim of the present study was to explore the pharmaco-mechanistic efficacy of allantoin against commonly harmful agents that cause injuries to the stomach. Ethanol, indomethacin, and stress-induced gastric ulcer models were adopted, in addition to pylorus ligature, a quantification of vascular permeability, glutathione (GSH), gastric adhered mucus, prostaglandin (PGE2), pro-inflammatory cytokines levels, myeloperoxidase (MPO), and catalase (CAT) activities. The gastric lesions were examined by gross, histological, and ultrastructural features. The results showed that treatment with allantoin (60mg/kg, per oral) reduced the gastric ulcer formation in all models. Furthermore, allantoin reduced the parameters of gastric acid secretion and attenuated both the vascular permeability and MPO activity. The levels of pro-inflammatory cytokines were also reduced, accompanied by a restoration of CAT activity and GSH levels. Notably, allantoin treatment preserved the gastric-adhered mucus and PGE2 levels after ethanol administration. Microscopic and ultrastructural analysis revealed that allantoin maintained tissue integrity and prevented morphological changes in cells caused by ethanol. In summary, we demonstrated for the first time that allantoin possesses gastroprotective activity through anti-inflammatory, anti-oxidative, antisecretory, and cytoprotective mechanisms. The antisecretory and cytoprotective mechanisms are probably associated with an increase in PGE2 levels.

Aging-Induced Biological Changes and Cardiovascular Diseases.

Aging is characterized by functional decline in homeostatic regulation and vital cellular events. This process can be linked with the development of cardiovascular diseases (CVDs). In this review, we discussed aging-induced biological alterations that are associated with CVDs through the following aspects: (i) structural, biochemical, and functional modifications; (ii) autonomic nervous system (ANS) dysregulation; (iii) epigenetic alterations; and (iv) atherosclerosis and stroke development. Aging-mediated structural and biochemical modifications coupled with gradual loss of ANS regulation, vascular stiffening, and deposition of collagen and calcium often disrupt cardiovascular system homeostasis. The structural and biochemical adjustments have been consistently implicated in the progressive increase in mechanical burden and functional breakdown of the heart and vessels. In addition, cardiomyocyte loss in this process often reduces adaptive capacity and cardiovascular function. The accumulation of epigenetic changes also plays important roles in the development of CVDs. In summary, the understanding of the aging-mediated changes remains promising towards effective diagnosis, discovery of new drug targets, and development of new therapies for the treatment of CVDs.