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Background. Oral sex is postulated to be a risk factor for the introduction of bacteria into the amniotic cavity. Common oropharyngeal bacteria have been implicated in reports of second trimester chorioamnionitis via ascending vaginal transmission following oral sex. Dental scaling can also introduce these pathogens into the blood stream, allowing hematogenous spread of oral pathogens to the fetoplacental unit in pregnant patients. Case. We report a case of Streptococcus mitis chorioamnionitis at 21 weeks and 5 days’ gestation in a patient whose only risk factors were recent dental scaling and recent oral sex with a partner known to have periodontal disease. Conclusion. Bacterial chorioamnionitis should be considered in the differential diagnosis of preterm labour. Oral sex and dental procedures may be risk factors for chorioamnionitis.

Introduction: EAT is an independent factor in coronary artery disease (CAD). The objective of the current study was to define an echocardiographic cut-off point for EAT and to determine its diagnostic value in predicting the increase in CAD risk. Methods: Two hundred patients underwent coronary artery angiography for diagnosis of CAD and transthoracic echocardiography for measurement of EAT on the right ventricle (RV), RV apex and RV outlet tract. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the EAT cut-off points in the three above-mentioned areas for predicting the severity of CAD were measured. The relation between the EAT and CAD risk factors was evaluated as well. Results: EAT was independent from gender, height, hypertension, diabetes, HDL, total cholesterol, ejection fraction, acute coronary syndrome, and the location of the coronary artery stenosis in the coronary artery in all three anatomical areas. EAT on RV and RV apex had a significant relation with CAD (P ≤ 0.05). Overall, RV EAT≥ 10 mm and RV apex EAT ≥ 8 mm had sensitivity and PPV of more than 70% in predicting coronary stenosis ≥ 50% and acute coronary syndrome (ACS) and RVOT EAT ≥ 13 mm is of PPV=83.5% for predicting coronary stenosis ≥ 50%. Conclusion: EAT thickness has an acceptable diagnostic value for predicting severe coronary artery stenosis and ACS. Therefore, non-invasive EAT thickness measurement could be of great assistance to clinicians for detecting the patients at risk and helping them to undergo supplementary evaluations with invasive approaches.

Flaxseed is an ancient commercial oil that historically has been used as a functional food to lower cholesterol levels. However, despite its longstanding treatment, there is currently a lack of scientific evidence to support its role in the management of cardiac remodeling. This study aimed to address this gap in knowledge by examining the molecular mechanism of standardized flaxseed oil in restoring cardiac remodeling in the heart toxicity vivo model. The oil fraction was purified, and the major components were standardized by qualitative and quantitative analysis. In vivo experimental design was conducted using isoproterenol ISO (85 mg/kg) twice subcutaneously within 24 h between each dose. The rats were treated with flaxseed oil fraction (100 mg/kg orally) and the same dose was used for omega 3 supplement as a positive control group. The GC-MS analysis revealed that α-linolenic acid (24.6%), oleic acid (10.5%), glycerol oleate (9.0%) and 2,3-dihydroxypropyl elaidate (7%) are the major components of oil fraction. Physicochemical analysis indicated that the acidity percentage, saponification, peroxide, and iodine values were 0.43, 188.57, 1.22, and 122.34 respectively. As compared with healthy control, ISO group-induced changes in functional cardiac parameters. After 28-day pretreatment with flaxseed oil, the results indicated an improvement in cardiac function, a decrease in apoptosis, and simultaneous prevention of myocardial fibrosis. The plasma levels of BNP, NT-pro-BNP, endothelin-1, Lp-PLA2, and MMP2, and cTnI and cTn were significantly diminished, while a higher plasma level of Topo 2B was observed. Additionally, miRNA - 1 and 29b were significantly downregulated. These findings provide novel insight into the mechanism of flaxseed oil in restoring cardiac remodeling and support its future application as a cardioprotective against heart diseases., (© 2023. The Author(s).)

Ephedra is one of the oldest known medicinal plants and the largest genera of the Ephedraceae family. In vivo antitumor evaluation of Ephedra foeminea revealed that ethyl acetate (EtOAc) was the most bioactive fraction. Bio-guided fractionation of EtOAc fraction afforded nine compounds isolated for the first time from the plant species. Macrocyclic spermine alkaloids (1,9), proanthocyanidins (2,4,5), quinoline alkaloids (7,8), phenolic (3), and nucleoside (6) were identified and elucidated by spectroscopic analyses including 1D and 2D NMR, ESI-MS-MS spectrometry. The tested compounds exhibited moderate anticancer activity, except for the kynurenic acid derivative (6-mKYNA) which showed significant cytotoxicity and remarkable inhibition of CA-19.9 and CA-125 tumor biomarkers. In-silico study was conducted to determine the anti-proliferative mechanism of 6-mKYNA by using the CK2 enzyme active site. Moreover, the ADME computational study suggested that 6-mKYNA is an effective candidate with a promising pharmacokinetic profile and therapeutic potential against various types of cancer.

Bottle gourd (BG) oil (family Cucurbitaceae) has several pharmacological activities including a reduction of the hazard of cardiovascular and atherosclerosis conditions. This work aimed to develop and optimize self-dispersing lipid formulations (SDLFs) of BG oil by applying a full 3 2 factorial design. The formulation variables (oil concentration and surfactant mixture ratio) showed an obvious impact on the characters of the prepared BG-SDLFs including droplet size (DS), polydispersity index (PDI), emulsification time (ET), and transmission percentage (Tr%). The optimum BG-SDLF composed of 30% oil and Tween 80/Cremophor ® RH40 (1:1) showed good emulsification characteristics and a better drug release profile compared with BG oil. In vivo study in isoproterenol-injected rats showed that BG oil and the optimized BG-SDLF improved cardiac function, by elevating the miRNA-23a gene expression level and decreasing miRNA-21 gene expression. They also caused the inhibition of the plasma B-type natriuretic peptide (BNP), N-terminal proatrial natriuretic peptide (NT-pro-BNP), cystatin c, galectin-3, lipoprotein-associated phospholipase A2 (Lp-PLA2), matrix metallopeptidase 2 (MMP2), cardiac troponin I (cTnI), and cardiac troponin T (cTnT). Our study demonstrated that BG oil and the optimized BG-SDLF provided a cardioprotection against isoproterenol-induced cardiac toxicity with better results in groups treated with the optimized BG-SDLF.

The current work was conducted to synthesize several novel anti-inflammatory quinazolines having sulfamerazine moieties as new 3CLpro, cPLA2, and sPLA2 inhibitors. The thioureido derivative 3 was formed when compound 2 was treated with sulfamerazine. Also, compound 3 was reacted with NH 2 -NH 2 in ethanol to produce the N-aminoquinazoline derivative. Additionally, derivative 4 was reacted with 4-hydroxy-3-methoxybenzaldehyde, ethyl chloroacetate, and/or diethyl oxalate to produce quinazoline derivatives 5 , 6 , and 12 , respectively. The results of the pharmacological study indicated that the synthesized 4 - 6 and 12 derivatives showed good 3CLpro, cPLA2, and sPLA2 inhibitory activity. The IC 50 values of the target compounds 4 - 6 , and 12 against the SARS-CoV-2 main protease were 2.012, 3.68, 1.18, and 5.47 µM, respectively, whereas those of baicalein and ivermectin were 1.72 and 42.39 µM, respectively. The IC 50 values of the target compounds 4 - 6 , and 12 against sPLA2 were 2.84, 2.73, 1.016, and 4.45 µM, respectively, whereas those of baicalein and ivermectin were 0.89 and 109.6 µM, respectively. The IC 50 values of the target compounds 4 - 6 , and 12 against cPLA2 were 1.44, 2.08, 0.5, and 2.39 µM, respectively, whereas those of baicalein and ivermectin were 3.88 and 138.0 µM, respectively. Also, incubation of lung cells with LPS plus derivatives 4 - 6 , and 12 caused a significant decrease in levels of sPLA2, cPLA2, IL-8, TNF-α, and NO. The inhibitory activity of the synthesized compounds was more pronounced compared to baicalein and ivermectin. In contrast to ivermectin and baicalein, bioinformatics investigations were carried out to establish the possible binding interactions between the newly synthesized compounds 2 - 6 and 12 and the active site of 3CLpro. Docking simulations were utilized to identify the binding affinity and binding mode of compounds 2 - 6 and 12 with the active sites of 3CLpro, sPLA2, and cPLA2 enzymes. Our findings demonstrated that all compounds had outstanding binding affinities, especially with the key amino acids of the target enzymes. These findings imply that compound 6 is a potential lead for the development of more effective SARS-CoV-2 Mpro inhibitors and anti-COVID-19 quinazoline derivative-based drugs. Compound 6 was shown to have more antiviral activity than baicalein and against 3CLpro. Furthermore, the IC 50 value of ivermectin against the SARS-CoV-2 main protease was revealed to be 42.39 µM, indicating that it has low effectiveness.

In this study, we investigated the polyphenolic profile of Pachira macrocarpa Schltdl. & Cham. by HPLC analysis and we also isolated three compounds from the ethyl acetate leaf extract, which were identified by different spectral data as vitexin 1, luteolin 2, and ferulic acid 3. Moreover, we investigated the three isolated compounds and the plant extract for their therapeutic potential against AlCl 3 exposure-induced neurotoxicity in rats. This investigation aims to determine whether vitexin, luteolin, and ferulic acid in Pachira macrocarpa Schltdl. & Cham. extract ( P. macrocarpa ) have the ability to treat AlCl 3 -induced brain toxicity in rats. Six groups of rats were created: group 1 (normal group), group 2 treated with AlCl 3 , and groups 3, 4, 5, and 6 treated with AlCl 3 with vitexin, luteolin, ferulic acid, and P. macrocarpa extract, respectively, for 28 days. Neurotoxicity was assessed by measuring plasma IL-8 and IL-33 as well as brain superoxide dismutase (SOD), glutathione reductase (GSR), B-cell lymphoma-2 (BcL-2), B-cell lymphoma-2 associated-x (Bax), and neurogranin using the ELISA technique and c-Jun N-terminal kinase (JNK), miRNA-125b, and miRNA-132 levels using western blot and PCR. HPLC analysis identified major phenolics and flavonoids. Among the phenolics identified, chlorogenic acid was prevalent (2159.14 μg/g), and regarding flavonoids, rutin was prevalent (204.69 μg/g). A significant elevation of IL-8 and IL-33 as well as brain Bax, neurogranin, and JNK levels and of miRNA-125b gene expression levels was observed following AlCl 3 exposure. However, significant depletion of SOD, GSR, BcL-2, total protein, and miRNA-132 gene expression was observed in AlCl 3 -treated rats. Administration of the P. macrocarpa extract and its isolated compounds significantly increased SOD, GSR, BcL-2, total protein, and miRNA132 gene expression and decreased IL-8 and IL-33 as well as brain Bax, neurogranin, and JNK levels and brain miRNA-125b gene expression compared to AlCl 3 -treated rats. P. macrocarpa extract and its isolated compounds ameliorated AlCl 3 -induced oxidative stress and neurotoxicity in rats., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The present study aimed to develop fast melting tablets (FMTs) using silymarin (SM) owing to FMTs rapid disintegration and dissolution. FMTs represent a pathway to help patients to increase their compliance level of treatment via facile administration without water or chewing beside reduction cost. One of the methods for FMTs formulation is lyophilization. Optimization of SM-FMTs was developed via a 3 2 factorial design. All prepared SM-FMTs were evaluated for weight variation, thickness, breaking force, friability, content uniformity, disintegration time (DT), and % SM released. The optimized FMT formula was selected based on the criteria of scoring the fastest DT and highest % SM released after 10 min (Q 10 ). Optimized FMT was subjected to Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) besides investigating its lung-protective efficacy. All SM-FMT tablets showed acceptable properties within the pharmacopeial standards. Optimized FMT (F7) scored a DT of 12.5 ± 0.64 Sec and % SM released at Q 10 of 82.69 ± 2.88%. No incompatibilities were found between SM and excipients, it showed a porous structure under SEM. The optimized formula decreased cytokines, up-regulated miRNA133a, and down-regulated miRNA-155 and COX-2 involved in the protection against lung toxicity prompted by HgCl 2 in a manner comparable to free SM at the same dosage.

Saussurea costus is a plant traditionally used for the treatment of several ailments. Our study accomplished the UPLC/T-TOF-MS/MS analysis of a methanol extract of Saussurea costus roots (MESC), in addition to lipoidal matter determination and assessment of its in vivo hepatoprotective activity. In this study, we were able to identify the major metabolites in MESC rather than the previously known isolated compounds, improving our knowledge of its chemical constituents. The flavones apigenin, acacetin, baicalein, luteolin, and diosmetin, and the flavonol aglycones quercetin, kaempferol, isorhamnetin, gossypetin, and myricetin and/or their glycosides and glucuronic derivatives were the major identified compounds. The hepatoprotective activity of MESC was evaluated by measuring catalase activity using UV spectrophotometry, inflammatory cytokines and apoptotic markers using ELISA techniques, and genetic markers using PCR. Paracetamol toxicity caused a significant increase in plasma caspase 2, cytokeratin 18 (CK18), liver tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), miRNA-34a, and miRNA-223, as well as a significant decrease in liver catalase (CAT) activity and in the levels of liver nuclear factor 1α (HNF-1α), sirtuin-1, and C/ebpα. Oral pretreatment with MESC (200 mg/kg) showed a significant decrease in caspase 2, CK18, TNF-α, IL-6 and a significant increase in liver CAT activity. MESC decreased the levels of liver miRNA-34a and miRNA-223 and induced HNF-1α, sirtuin-1, and C/ebpα gene expression. The histological examination showed a significant normalization in rats pretreated with MESC. Our findings showed that Saussurea costus may exert a potent hepatoprotective activity through the modulation of the expression of cellular cytokines, miRNA-34a, and miRNA-223.

Background: Astaxanthin suppressed obesity in rats fed with high-fat diet (HFD) via the restriction of adipose tissue build-out, therefore, improving insulin sensitivity and inflammation. Metformin reduces insulin resistance and may reduce weight., Aim: Investigation of the effects of astaxanthin and metformin in obesity prompted by a high-fat diet., Objective: The present article investigates the effects of astaxanthin and metformin in obesity prompted by a high-fat diet in rats through measuring miRNA222 and 378., Materials: The rats were classified into four classes containing ten albino rats each: Group I (Normal group): nourished with ordinary diet for 8weeks. Group II (Control positive): nourished with a high-fat diet for 8 weeks. Group III: nourished with astaxanthin (50mg/kg)(1/40 LD50) orally plus a high-fat diet for 8weeks. Group IV: nourished with metformin (500mg/kg) orally plus a high-fat diet for 8 weeks., Methods: Leptin, adiponectin, calprotectin and interleukin 6 (IL-6) were assessed by rat-specific ELISA kits. Tumor necrosis factor-alpha (TNF-α), miRNA222 and miRNA378 expressions were quantified by quantitative real-time PCR., Results: Astaxanthin and metformin have anti-obesity and antioxidant actions and significantly decreased the weight of the body, glucose, insulin, triglycerides, total cholesterol, triglycerides and leptin, as well as plasma calprotectin & IL-6 and increased HDL-C and adiponectin. The liver TNF-α gene expression, adipose tissue miRNA222 and miRNA378 expression were decreased compared to HFD control rats., Discussion and Conclusion: Astaxanthin has regulated the aberrant expression of miRNA222 and 378 that may be related to hyperlipidemia and insulin resistance. Accordingly, astaxanthin deserves a clinical trial in the future due to its effects on miRNAs involved in obesity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In response to the urgent need to control Coronavirus disease 19 (COVID-19), this study aims to explore potential anti-SARS-CoV-2 agents from natural sources. Moreover, cytokine immunological responses to the viral infection could lead to acute respiratory distress which is considered a critical and life-threatening complication associated with the infection. Therefore, the anti-viral and anti-inflammatory agents can be key to the management of patients with COVID-19. Four bioactive compounds, namely ferulic acid 1 , rutin 2 , gallic acid 3 , and chlorogenic acid 4 were isolated from the leaves of Pimenta dioica (L.) Merr (ethyl acetate extract) and identified using spectroscopic evidence. Furthermore, molecular docking and dynamics simulations were performed for the isolated and identified compounds ( 1 - 4 ) against SARS-CoV-2 main protease (Mpro) as a proposed mechanism of action. Furthermore, all compounds were tested for their half-maximal cytotoxicity (CC 50 ) and SARS-CoV-2 inhibitory concentrations (IC 50 ). Additionally, lung toxicity was induced in rats by mercuric chloride and the effects of treatment with P. dioca aqueous extract, ferulic acid 1 , rutin 2 , gallic acid 3 , and chlorogenic acid 4 were recorded through measuring TNF-α, IL-1β, IL-2, IL-10, G-CSF, and genetic expression of miRNA 21-3P and miRNA-155 levels to assess their anti-inflammatory effects essential for COVID-19 patients. Interestingly, rutin 2 , gallic acid 3 , and chlorogenic acid 4 showed remarkable anti-SARS-CoV-2 activities with IC 50 values of 31 µg/mL, 108 μg/mL, and 360 µg/mL, respectively. Moreover, the anti-inflammatory effects were found to be better in ferulic acid 1 and rutin 2 treatments. Our results could be promising for more advanced preclinical and clinical studies especially on rutin 2 either alone or in combination with other isolates for COVID-19 management.

Oleogel consists of hydrophobic solvent and an oleogelator. In this study, attempts were made to study the influence of Celecoxib solubility, concentration and dispersability on its release, absorption, and biological performance. Oleogels were prepared to study the formulation variables on its stability and release. Castor oil was selected as the oil and the oleogelator concentration was 4.5% w/w. F3 revealed the highest release and stability compared to other formulae. The percent permeated across the rat intestine showed a 7.5-fold increase over free Celecoxib, and its lifetime was found to be greater than 18 months. The efficacy of free Celecoxib and oleogel formulae to treat rats with ulcerative colitis was done via the induction of ulcerative colitis (UC) through administration of 5% dextran sodium sulphate (DSS). Celecoxib besides its formulae significantly reduced the release of Leucine rich 2 glycoprotein (LRG), Myeloperoxidase (MPO), Tumor necrosis factor-α (TNF-α), proinflammatory cytokine expression, High mobility group box 1 (HMGB1), Nuclear factor kappa B (NF-ΚB), Trefoil Factor 3 (TFF3), Metalloproteinase-3 (MMP3), and miRNA31. Moreover, F3 significantly increased the colonic cAMP in DSS treated rats and reduced the intestinal inflammation beside healing of mucosa and restitution of the epithelium of the gastrointestinal tract.

Acute myocardial infarction is a major cause of death and disability worldwide. This study was designed to elucidate the effect of resveratrol (RES) in isoproterenol (ISO)-challenged myocardial injury in rats. Male Sprague-Dawley rats were randomly allocated to four groups (10 rats/group): negative, control positive ISO (85 mg/kg), Propranolol/ISO, and RES/ISO. RES (50 mg/kg) improved plasma lactate dehydrogenase, creatine kinase, and cardiac troponin T; brain natriuretic peptide, interleukin-10, vascular endothelial growth factor, and transforming growth factor- β 1; as well as cardiac superoxide dismutase, malondialdehyde, and total protein kinase-1 (Akt-1) levels. In addition, RES reduced the expression of cardiac inducible nitric oxide synthase and microRNA-34a, as well as p38 mitogen-activated protein kinase levels compared with positive control group. In conclusion, RES could reduce the degree of MI induced by ISO by improving the antioxidant, antiapoptotic, and anti-inflammatory capacities of the body.

Myocardial infarction (MI) is the principal cause of death in many countries. Silymarin (SM) is a herbal antioxidant and can be efficiently used in preventing cardiovascular diseases (CVDs). The study is aimed to enhance the absorption rate and biological activity of SM by using liquisolids besides investigating the cardioprotective activity of SM and its selected liquisolid formula against isoproterenol prompted cardiotoxicity in rats. Eight formulae were prepared according to (2 3 ) full-factorial design. The effect of viscosity increasing agent type and concentration, as well as the carrier/coat ratio on the dissolution rate and angle of repose were studied. All formulae were tested for content uniformity, micromeritic properties, dissolution performance besides the evaluation of its physicochemical properties, and scanning electron microscopy (SEM). Based on the factorial design outcomes, the highest desirability was obtained from F3 with excipient ratio value (R) of 20%, dissolution rate at Q 5 min of 26.9%, and angle of repose of 19. Oral administration of F3 liquisolid and SM revealed a significant protective efficacy against the modification of cardiac plasma markers, brain natriuretic peptide (BNP), interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)-β1 besides cardiac superoxide dismutase (SOD), malondialdehyde (MDA), and total protein kinase-1 (Akt-1) levels. Additionally, they minimized cardiac inducible nitric oxide synthase (iNOS), microRNA-34a (miR-34a), and p38 mitogen-activated protein kinase (p38-MAPK) levels. In conclusion, F3 liquisolid compact possessed an overall pronounced results over pure SM reckoned to its enhanced solubility and efficacy.

The present study demonstrates a preparative medium-pressure liquid chromatography (MPLC) method for isolation of Morin besides evaluating its efficacy in comparison with its self-nanoemulsifying drug delivery (SNEDD) and nanoemulsion (NE) systems against in-vivo HgCl 2 -induced lung toxicity in rats. Morin was isolated from hydroalcoholic (70%) extract of Psidium guajava leaves by MPLC. The purity (> 90%) was done using HPLC. Screening of Morin solubility was studied to identify the components of each system. The prepared formulae were assessed for their thermodynamic stability, rheological properties, emulsification time, size, zeta potential beside its dissolution. The selected formulae according to the smallest size, highest zeta potential, and release at Q 10 min were assessed for their morphology by transmission electron microscopy (TEM) and protective potential against in-vivo HgCl 2 -induced lung toxicity in rats. All formulae were stable with Newtonian flow, emulsification time was (< 134 ± 10 s), size (< 40 nm) with zeta potential (> - 10.36 ± 0.99 mV). The extent of free Morin dissolved from capsule showed significantly the lowest percent released (22.21 ± 1.45%) while in case of SNEDDs and NEs (> 55% dissolved). The morphology of the selected Morin formulae showed spherical shape within the nano-range. Supplementation of Morin and its formulae to rats caused significant decrease in C-reactive protein, hepatoglobin, hydroproxide, lung nitric oxide, tumor necrosis factor-α, immunoglobulin (E and G), histamine, malondialdehyde, and interleukin-6 gene expression while significant increase in immunoglobulin A, caspase-3, catalase, and glutathione peroxidase compared to HgCl 2 . SNEDD and NE formulae could ameliorate lung toxicity in a mechanism related to their antioxidant and anti-inflammatory potential.

Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) have been reported to play an important role in tumor proliferation. This study aimed to investigate the validity of measuring IGFs and specific IGFBPs in the serum of Egyptian children with acute lymphoblastic leukemia (ALL) as additional markers in diagnosis and follow-up of the disease. IGF-I, IGF-II, IGFBP-2, and IGFBP-3 were determined in the sera of 33 ALL patients at time of diagnosis and after an intensification phase of chemotherapy (IPC) that lasts about 6 months as well as in 15 healthy children as a control group using enzyme-linked immunosorbent assay (ELISA) technique. At time of diagnosis, serum IGF-I, IGF-II, and IGFBP-3 were significantly lower than those in the control group. After IPC, serum IGF-I and IGF-II returned to their normal levels, while serum IGFBP-3 was still decreased. On the other hand, serum IGFBP-2 was significantly higher than those in the control group at diagnosis, but returned to normal value after IPC. In conclusion, the changes in IGF system could be useful to support diagnosis and follow-up of children with ALL.