The art of healing hearts: Mastering advanced RNA therapeutic techniques to shape the evolution of cardiovascular medicine in biomedical science.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide and are associated with increasing financial health burden that requires research into novel therapeutic approaches. Since the early 2000s, the availability of next-generation sequencing techniques such as microRNAs, circular RNAs, and long non-coding RNAs have been proven as potential therapeutic targets for treating various CVDs. Therapeutics based on RNAs have become a viable option for addressing the intricate molecular pathways that underlie the pathophysiology of CVDs. We provide an in-depth analysis of the state of RNA therapies in the context of CVDs, emphasizing various approaches that target the various stages of the basic dogma of molecular biology to effect temporary or long-term changes. In this review, we summarize recent methodologies used to screen for novel coding and non-coding RNA candidates with diagnostic and treatment possibilities in cardiovascular diseases. These methods include single-cell sequencing techniques, functional RNA screening, and next-generation sequencing.Lastly, we highlighted the potential of using oligonucleotide-based chemical products such as modified RNA and RNA mimics/inhibitors for the treatment of CVDs. Moreover, there will be an increasing number of potential RNA diagnostic and therapeutic for CVDs that will progress to expand for years to come.

Therapeutic effects of genistein in experimentally induced ulcerative colitis in rats via affecting mitochondrial biogenesis.

Ulcerative colitis (UC) is an inflammatory bowel disease that affects the mucosa of the colon, resulting in severe inflammation and ulcers. Genistein is a polyphenolic isoflavone present in several vegetables, such as soybeans and fava beans. Therefore, we conducted the following study to determine the therapeutic effects of genistein on UC in rats by influencing antioxidant activity and mitochondrial biogenesis and the subsequent effects on the apoptotic pathway. UC was induced in rats by single intracolonic administration of 2 ml of 4% acetic acid. Then, UC rats were treated with 25-mg/kg genistein. Colon samples were obtained to assess the gene and protein expression of nuclear factor erythroid 2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), peroxisome proliferator-activated receptor-gamma coactivator (PGC-1), mitochondrial transcription factor A (TFAM), B-cell lymphoma 2 (BCL2), BCL2-associated X (BAX), caspase-3, caspase-8, and caspase-9. In addition, colon sections were stained with hematoxylin/eosin to investigate the cell structure. The microimages of UC rats revealed inflammatory cell infiltration, hemorrhage, and the destruction of intestinal glands, and these effects were improved by treatment with genistein. Finally, treatment with genistein significantly increased the expression of PGC-1, TFAM, Nrf2, HO-1, and BCL2 and reduced the expression of BAX, caspase-3, caspase-8, and caspase-9. In conclusion, genistein exerted therapeutic effects against UC in rats. This therapeutic activity involved enhancing antioxidant activity and increasing mitochondrial biogenesis, which reduced cell apoptosis.

Efficacy and Safety of Empagliflozin in Type 2 Diabetes Mellitus Saudi Patients as Add-On to Antidiabetic Therapy: A Prospective, Open-Label, Observational Study.

The Saudi Food and Drug Authority (SFDA) approved sodium-glucose cotransporter-2 (SGLT2) inhibitors in 2018. The efficacy and safety of empagliflozin (EMPA) have been confirmed in the U.S., Europe, and Japan for patients with type 2 diabetes mellitus (T2DM); however, analogous evidence is lacking for Saudi T2DM patients. Therefore, the current study aimed to assess the efficacy and safety of EMPA in Saudi patients (n = 256) with T2DM. This is a 12-week prospective, open-label, observational study. Adult Saudi patients with T2DM who had not been treated with EMPA before enrolment were eligible. The exclusion criteria included T2DM patients less than 18 years of age, adults with type one diabetes, pregnant women, paediatric population. The results related to efficacy included a significant decrease in haemoglobin A1c (HbA1c) (adjusted mean difference −0.93% [95% confidence interval (CI) −0.32, −1.54]), significant improvements in fasting plasma glucose (FPG) (−2.28 mmol/L [95% CI −2.81, −1.75]), and a reduction in body weight (−0.874 kg [95% CI −4.36, −6.10]) following the administration of 25 mg of EMPA once daily as an add-on to ongoing antidiabetic therapy after 12 weeks. The primary safety endpoints were the change in the mean blood pressure (BP) values, which indicated significantly reduced systolic and diastolic BP (−3.85 mmHg [95% CI −6.81, −0.88] and −0.06 mmHg [95% CI −0.81, −0.88], respectively) and pulse rate (−1.18 [95% CI −0.79, −3.15]). In addition, kidney function was improved, with a significant reduction in the urine albumin/creatinine ratio (UACR) (−1.76 mg/g [95% CI −1.07, −34.25]) and a significant increase in the estimated glomerular filtration rate (eGFR) (3.54 mL/min/1.73 m2 [95% CI 2.78, 9.87]). Furthermore, EMPA reduced aminotransferases (ALT) in a pattern (reduction in ALT > AST). The adjusted mean difference in the change in ALT was −2.36 U/L [95% CI −1.031, −3.69], while it was −1.26 U/L [95% CI −0.3811, −2.357] for AST and −1.98 U/L [95% CI −0.44, −3.49] for GGT. Moreover, in the EMPA group, serum high-density lipoprotein (HDL) significantly increased (0.29 mmol/L [95% CI 0.74, 0.15]), whereas a nonsignificant increase was seen in low-density lipoprotein (LDL) (0.01 mmol/L [95% CI 0.19, 0.18]) along with a significant reduction in plasma triglyceride (TG) levels (−0.43 mmol/L [95% CI −0.31, −1.17]). Empagliflozin once daily is an efficacious and tolerable strategy for treating Saudi patients with insufficiently controlled T2DM as an add-on to ongoing antidiabetic therapy.

Evaluation of In Vitro Antiprotease Activity of Selected Traditional Medicinal Herbs in Dentistry and Its In Silico PASS Prediction.

Background: Dental/oral diseases are one of the significant public health problems globally. Herbal medicines for managing oral diseases are considered an effective alternative to synthetic compounds due to their lower side effect. Azadirachta indica, Terminalia chebula, Camellia sinensis, and Piper nigrum are used to control and prevent oral inflammations in dentistry. In this study, we have evaluated the protease inhibition activity of these plant extracts, and further, the binding mode of the active ingredient of these plants with trypsin was studied using molecular docking. Methods: In this study, protease inhibition activity was carried out using aqueous extracts of the plant parts such as Azadirachta indica (neem) twig, Terminalia chebula (Haritaki) fruit, Camellia sinensis (green tea) powder, and Piper nigrum (kali miri) seed. Next, to explore the binding mode of active ingredients azadirachtin, chebuligenic acid, catechin, and piperine with trypsin, we employed a molecular docking study using AutoDock4.2. Results: The results revealed that the Azadirachta indica plant extract showed an IC50 value of 96.19 µg mL-1, Camellia sinensis IC50 value of 188.50 µg mL-1, Piper nigrum IC50 value of 371.20 µg mL-1, and Terminalia chebula IC50 value of 639.48 µg mL-1, when compared with standard drug diclofenac sodium, had IC50 value 93.00 µg mL-1. Further, the docking result reveals that all the main active ingredients of these plants have significant binding affinity and prefer the same binding pocket of trypsin. Conclusion: Hence, our results show the importance of traditional plants Azadirachta indica, Terminalia chebula, green tea, and Piper nigrum to control oral disease conditions. As they show significant protease inhibition activity, hence, the active ingredient could act as a potential anti-inflammatory agent and further help to prevent or control oral disease conditions such as gingivitis and periodontitis.

Relationship and inter observer agreement of tooth and face forms in a Saudi subpopulation.

OBJECTIVE: To determine the relationship of tooth form with the face form by different observers and further investigate the inter observer agreement on tooth forms, face forms, their relationship among male Saudis. STUDY DESIGN: A comparative cross-sectional study. PLACE AND DURATION OF STUDY: Department of Prosthodontics, College of Dentistry, King Saud University, Riyadh, KSA, from February till August 2013. METHODOLOGY: Ninety four male participants aged 18 - 35 years were randomly recruited for the study. Full-face and anterior teeth (intraoral) digital photographs in the frontal plane were recorded. The outline tracings of the face and the tooth were obtained using Autocad (version 2010) software. The outline of the tooth was enlarged proportionately, without altering the length to width ratio to fit the face outline. The outlines were then evaluated visually by 6 prosthodontists and results were tabulated. RESULTS: The most common type of face form (49.65%) and tooth form (56.38%) was square tapering. Using the visual method, a good relationship (31.41%), moderate relationship (35.31%), weak relationship (19.68%) and no relationship (13.65%) between the tooth form and face form was found by the observers. Overall kappa for inter observer agreement on face form, tooth form and their relationship was 0.24, 0.17 and 0.26 respectively. The kappa values showed a fair agreement between the observers. CONCLUSION: The study results indicated that there was no highly defined relationship between the tooth form and face form in the studied Saudi subpopulation. A fair agreement was found between the observers for classifying the tooth forms, face froms and their relationship.