Phytochemical constituents,biological activities,and health‐promoting effects of the genus Origanum

Origanum species are mostly distributed around the Mediterranean, Euro‐Siberian, and Iran‐Siberian regions. Since time immemorial, the genus has popularly been used in Southern Europe, as well as on the American continent as a spice now known all over the world under the name “oregano” or “pizza‐spice.” Origanum plants are also employed to prepare bitter tinctures, wines, vermouths, beer, and kvass. The major components of Origanum essential oil are various terpenes, phenols, phenolic acids, and flavonoids with predominant occurrence of carvacrol and thymol (with reasonable amounts of p‐cymen and ‐terpinene) or of terpinene‐4‐ol, linalool, and sabinene hydrate. Many species of Origanum genus are used to treat kidney, digestive, nervous, and respiratory disorders, spasms, sore throat, diabetes, lean menstruation, hypertension, cold, insomnia, toothache, headache, epilepsy, urinary tract infections, etc. Origanum essential oil showed potent bioactivities owing to its major constituents' carvacrol, thymol, and monoterpenes. Several preclinical studies evidenced its pharmacological potential as antiproliferative or anticancer, antidiabetic, antihyperlipidemic, anti‐obesity, renoprotective, antiinflammatory, vasoprotective, cardioprotective, antinociceptive, insecticidal, and hepatoprotective properties. Its nanotechnological applications as a promising pharmaceutical in order to enhance the solubility, physicochemical stability, and the accumulation rate of its essential oils have been investigated. However, Origanum has been reported causing angioedema, perioral dermatitis, allergic reaction, inhibition of platelet aggregation, hypoglycemia, and abortion. Conclusive evidences are still required for its clinical applications against human medical conditions. Toxicity analyses and risk assessment will aid to its safe and efficacious application. In addition, elaborate structure–activity studies are needed to explore the potential use of Origanum‐derived phytochemicals as promising drug candidates.     

Coronary computed tomography–angiography quantitative plaque analysis improves detection of early cardiac allograft vasculopathy: A pilot study

Cardiac allograft vasculopathy (CAV) is an increasingly important complication after cardiac transplant. We assessed the additive diagnostic benefit of quantitative plaque analysis in patients undergoing coronary computed tomography–angiography (CCTA). Consecutive patients undergoing CCTA for CAV surveillance were identified. Scans were visually interpreted for coronary stenosis. Semiautomated software was used to quantify noncalcified plaque (NCP), as well as its components. Optimal diagnostic cut‐offs for CAV, with coronary angiography as gold standard, were defined using receiver operating characteristic curves. In total, 36 scans were identified in 17 patients. CAV was present in 17 (46.0%) reference coronary angiograms, at a median of 1.9 years before CCTA. Median NCP (147 vs 58, P < .001), low‐density NCP (median 4.5 vs 0.9, P = .003), fibrous plaque (median 76.1 vs 31.1, P = .003), and fibrofatty plaque (median 63.6 vs 27.6, P < .001) volumes were higher in patients with CAV, whereas calcified plaque was not (median 0.0 vs 0.0, P = .510). Visual assessment of CCTA alone was 70.6% sensitive and 100% specific for CAV. The addition of total NCP volume increased sensitivity to 82.4% while maintaining 100% specificity. NCP volume is significantly higher in patients with CAV. The addition of quantitative analysis to visual interpretation improves the sensitivity for detecting CAV without reducing specificity.     

Biocompatible implant mimicking cartilage: A new horizon for reconstructive facial field

Cartilage is avascular with limited to no regenerative capacity, so its loss could be a challenge for reconstructive surgery. Current treatment options for damaged cartilage are also limited. In this aspect there is a tremendous need to develop an ideal cartilage-mimicking biomaterial that could repair maxillofacial defects. Considering this fact in this study we have prepared twelve silicone-based materials (using Silicone 40, 60, and 80) reinforced with hydroxyapatite, tri-calcium phosphate, and titanium dioxide which itself has proven their efficacy in several studies and able to complement the shortcomings of using silicones. Among the mechanical properties (Young’s modulus, tensile strength, percent elongation, and hardness), hardness of Silicone-40 showed similarities with goat ear (P > .05). Silicone peaks have been detected in FTIR. Both AFM morphology and SEM images of the samples confirmed more roughed surfaces. All the materials were nonhemolytic in hemocompatibility tests, but among the twelve materials S2, S3, S5, and S6 showed the least hemolysis. For all tested bacterial strains, adherence was lower on each material than that grown on the plain industrial silicone material which was used as a positive control. S2, S3, S5, and S6 samples were selected as the best based on mechanical characterizations, surface characterizations, in vitro hemocompatibility tests and bacterial adherence activity. So, outcomes of this present study would be promising when developing ideal cartilage-mimicking biocomposites and their emerging applications to treat maxillofacial defects due to cartilage damage.     

Covalent Triazine Frameworks Based on the First Pseudo-Octahedral Hexanitrile Monomer via Nitrile Trimerization: Synthesis,Porosity, and CO2 Gas Sorption Properties

Herein, we report the first synthesis of covalent triazine-based frameworks (CTFs) based on a hexanitrile monomer, namely the novel pseudo-octahedral hexanitrile 1,4-bis(tris(4′-cyano-phenyl)methyl)benzene 1 using both ionothermal reaction conditions with ZnCl₂ at 400 °C and the milder reaction conditions with the strong Brønsted acid trifluoromethanesulfonic acid (TFMS) at room temperature. Additionally, the hexanitrile was combined with different di-, tri-, and tetranitriles as a second linker based on recent work of mixed-linker CTFs, which showed enhanced carbon dioxide captures. The obtained framework structures were characterized via infrared (IR) spectroscopy, elemental analysis, scanning electron microscopy (SEM), and gas sorption measurements. Nitrogen adsorption measurements were performed at 77 K to determine the Brunauer-Emmett-Teller (BET) surface areas range from 493 m²/g to 1728 m²/g (p/p₀ = 0.01–0.05). As expected, the framework CTF-hex6 synthesized from 1 with ZnCl₂ possesses the highest surface area for nitrogen adsorption. On the other hand, the mixed framework structure CTF-hex4 formed from the hexanitrile 1 and 1,3,5 tricyanobenzene (4) shows the highest uptake of carbon dioxide and methane of 76.4 cm³/g and 26.6 cm³/g, respectively, at 273 K.     

Structural and Binding Studies of SAP-1 Protein With Heparin

SAP-1 is a low molecular weight cysteine protease inhibitor (CPI) which belongs to type-2 cystatins family. SAP-1 protein purified from human seminal plasma (HuSP) has been shown to inhibit cysteine and serine proteases and exhibit interesting biological properties, including high temperature and pH stability. Heparin is a naturally occurring glycosaminoglycan (with varied chain length) which interacts with a number of proteins and regulates multiple steps in different biological processes. As an anticoagulant, heparin enhances inhibition of thrombin by the serpin antithrombin III. Therefore, we have employed surface plasmon resonance (SPR) to improve our understanding of the binding interaction between heparin and SAP-1 (protease inhibitor). SPR data suggest that SAP-1 binds to heparin with a significant affinity (K_D = 158 nm ). SPR solution competition studies using heparin oligosaccharides showed that the binding of SAP-1 to heparin is dependent on chain length. Large oligosaccharides show strong binding affinity for SAP-1. Further to get insight into the structural aspect of interactions between SAP-1 and heparin, we used modelled structure of the SAP-1 and docked with heparin and heparin-derived polysaccharides. The results suggest that a positively charged residue lysine plays important role in these interactions. Such information should improve our understanding of how heparin, present in the reproductive tract, regulates cystatins activity.     

Prevalence and impact of comorbidities on disease prognosis among patients with COVID-19 in Bangladesh: A nationwide study amid the second wave

BackgroundSocio-demographics and comorbidities are involved in determining the severity and fatality in patients with COVID-19 suggested by studies in various countries, but study in Bangladesh is insufficient.AimsWe designed the study to evaluate the association of sociodemographic and comorbidities with the prognosis of adverse health outcomes in patients with COVID-19 in Bangladesh.MethodsA multivariate retrospective cohort study was conducted on data from 966 RT-PCR positive patients from eight divisions during December 13, 2020, to February 13, 2021. Variables included sociodemographic, comorbidities, symptoms, Charlson comorbidity index (CCI) and access to health facilities. Major outcome was fatality. Secondary outcomes included hospitalization, duration of hospital stay, requirement of mechanical ventilation and severity.ResultsMale (65.8%, 636 of 966) was predominant and mean age was 39.8 ± 12.6 years. Fever (79%), dry cough (55%), and loss of test/smell (51%) were frequent and 74% patients had >3 symptoms. Fatality was recorded in 10.5% patients. Comorbidities were found in 44% patients. Hypertension (21.5%) diabetes (14.6%), and cardiovascular diseases (11.3%) were most prevalent. Age >60 years (OR: 4.83, 95% CI: 2.45–6.49), and CCI >3 (OR: 5.48, 95% CI: 3.95–7.24) were predictors of hospitalizations. CCI >4 (aOR: 3.41, 95% CI: 2.57–6.09) was predictor of severity. Age >60 years (aOR: 3.77, 95% CI: 1.07–6.34), >3 symptoms (aOR: 2.14, 95% CI: 0.97–4.91) and CCI >3 vs. CCI <3 (aOR: 5.23, 95% CI: 3.77–8.09) were independently associated with fatality.ConclusionsIncreased age, >3 symptoms, increasing comorbidities, higher CCI were associated with increased hospitalization, severity and fatality in patients with COVID-19.     

A novel peroxisome proliferator-activated gamma (PPAR gamma) agonist,CLX-0921, has potent antihyperglycemic activity with low adipogenic potential

Agonists of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) are pharmacologically active antihyperglycemic agents that act by increasing peripheral tissue sensitivity to insulin. Many of these agonists have antihyperglycemic activity that is directly proportional to their ability to bind and activate PPAR gamma; however, recent data bring this relationship into question. In this report we describe a new PPAR gamma agonist, CLX-0921, that is derived from a natural product. This thiazolidinedione (TZD) has a spectrum of activity that differs from commercially available TZDs. It is a weak activator of PPAR gamma (EC(50) of 0.284 micromol/L) compared to rosiglitazone (EC(50) 0.009 micromol/L). Despite this difference, the drug maintains potent glucose uptake activity in vitro and glucose-lowering activity in vivo that is equipotent to that of rosiglitazone. Moreover, CLX-0921 showed a 10-fold reduction in in vitro adipogenic potential compared to rosiglitazone. CLX-0921 also increases glycogen synthesis, an activity not typically associated with rosiglitazone or pioglitazone. Thus CLX-0921 appears to have a distinct spectrum of activity relative to other TZDs.     

Steroidogenesis in rabbit preimplantation embryos.

Rabbit preimplantation embryos were flushed from the reproductive tract at 24 hr (1- to 2-cell stage), 48 hr (morula), 72 hr (morula), 96 hr (blastocyst), 120 hr (blastocyst), and 144 hr (blastocyst) post coitum. At 168 hr (early postimplantation period), gestation sacs were excised, frozen, and sectioned in a cryostat. Delta5-3beta-Hydroxysteroid dehydrogenase [3(or 17)beta-hydroxysteroid:NAD(P) oxidoreductase, EC 1.1.1.51] activity was determined histochemically in whole preimplantation embryos and in sectioned postimplantation embryos. 3beta-Hydroxysteroid dehydrogenase activity began at 48 hr and was sustained through the late blastocyst stage (144 hr), with the exception of a brief drop, possibly cessation, of activity at 72 hr. There was no activity at 168 hr. Since 3 beta-hydroxysteroid dehydrogenase is a key enzyme in the metabolism of steroid hormones, its presence is strong evidence for steroidogenesis. Only 144-hr preimplantation embryos were used to determine 17 beta-hydroxysteroid dehydrogenase (estradiol-17beta:NAD 17-oxidoreductase, EC 1.1.1.62) activity, which was present, suggesting synthesis of estrogen. By means of radioimmunoassay, 144-hr preimplantation embryos were found to contain estradiol-17beta. Other authors have shown that rabbit blastocysts contain progesterone and other steroids, and these embryos can synthesize steroids from non-steroid and steroid precursors. Therefore, our results plus those of others prove that rabbit preimplantation embryos synthesize steroid hormones. Our present and previous results (with rats, hamsters, and mice) suggest that the steroid hormones synthesized by the embryo are critical for preimplantation embryogenesis and for implantation of the lbastocyst.