Efficacy and safety of combination of empagliflozin and metformin with combination of sitagliptin and metformin during Ramadan: an observational study.

BACKGROUND: Management of diabetes during fasting is a clinical challenge. Sodium glucose co-transporter -2 inhibitors (SGLT2i) are considered safe with a low risk of hypoglycemia. However, studies on SGLT2i are scarce. This study was designed to compare the efficacy, safety, and tolerability of empagliflozin with metformin during Ramadan in comparison with sitagliptin and metformin. METHODS: It was a prospective, observational study, conducted at 11 different sites all across Pakistan on an outpatient basis during Ramadan (May 2021-June 2021). including 132 patients, 88 who received metformin and sitagliptin, and 44 patients who received metformin and empagliflozin. RESULTS: Patients of the SGLT-2i group experienced similar symptomatic hypoglycemic episodes (15.9%) as the sitagliptin group. There was an improvement in blood sugar levels after the use of SGLT-2i (RBS 181 ± 64 before Ramadan vs 162 ± 53 after Ramadan). HbA1c also improved after the use of SGLT-2i before and after Ramadan (7.2 ± 0.8 vs 6.9 ± 0.9 for Metformin + Empagliflozin and 7.8 ± 1.5 vs 7.6 ± 1.6 for Metformin and sitagliptin). Weight and BMI improved after the use of SGLT-2i (BMI 36.5 ± 4.8 before Ramadan and 33.7 ± 2.4 after Ramadan). There were no reported cases of urinary tract infection in the empagliflozin group. CONCLUSION: SGLT-2 inhibitors combined with metformin for patients with diabetes during Ramadan fasting is as effective, safe and well tolerated as DPP4 combined with metformin.

Synthesis, Molecular Modeling and Biological Evaluation of 5-arylidene-N,N-diethylthiobarbiturates as Potential α-glucosidase Inhibitors.

BACKGROUND: Barbituric acid derivatives are a versatile group of compounds which are identified as potential pharmacophores for the treatment of anxiety, epilepsy and other psychiatric disorders. They are also used as anesthetics and have sound effects on the motor and sensory functions. Barbiturates are malonylurea derivatives with a variety of substituents at C-5 position showing resemblance with nitrogen and sulfur containing compounds like thiouracil which exhibited potent anticancer and antiviral activities. Recently, barbituric acid derivatives have also received great interest for applications in nanoscience. OBJECTIVE: Synthesis of 5-arylidene-N,N-diethylthiobarbiturates, biological evaluation as potential α-glucosidase inhibitors and molecular modeling. METHODS: In the present study, N,N-Diethylthiobarbituric acid derivatives were synthesized by refluxing of N,N-diethylthiobarbituric acid and different aromatic aldehydes in distilled water. In a typical reaction; a mixture of N,N-diethylthiobarbituric acid 0.20 g (1 mmol) and 5-bromo-2- hydroxybenzaldehyde 0.199 g (1 mmol) mixed in 10 mL distilled water and reflux for 30 minutes. After completion of the reaction, the corresponding product 1 was filtered and dried and yield calculated. It was crystallized from ethanol. The structures of synthesized compounds 1-25 were carried out by using 1H, 13C NMR, EI spectroscopy and CHN analysis used for the determination of their structures. The α-glucosidase inhibition assay was performed as given by Chapdelaine et al., with slight modifications and optimization. RESULTS: Our newly synthesized compounds showed a varying degree of α-glucosidase inhibition and at least four of them were found as potent inhibitors. Compounds 6, 5, 17, 11 exhibited IC50 values (Mean±SEM) of 0.0006 ± 0.0002, 18.91 ± 0.005, 19.18 ± 0.002, 36.91 ± 0.003 µM, respectively, as compared to standard acarbose (IC50, 38.25 ± 0.12 µM). CONCLUSION: Our present study has shown that compounds 6, 5, 17, 11 exhibited IC50 values of 0.0006 ± 0.0002, 18.91 ± 0.005, 19.18 ± 0.002, 36.91 ± 0.003 µM, respectively. The studies were supported by in silico data analysis.

Coordinated effects of lead toxicity and nutrient deprivation on growth, oxidative status, and elemental composition of primed and non-primed rice seedlings.

Rice crop is highly susceptible to the toxic levels of lead (Pb) during early growth stages. Moreover, a sufficient availability of mineral nutrients is critical for survival of plants particularly under stressful conditions. An experiment was carried out to unravel the coordinated effects of Pb stress (1-mM PbCl2) and different nutrient treatments (sufficient nutrient supply, nitrogen (N) deprivation, phosphorus (P) deprivation, and potassium (K) deprivation) on morphological growth, reactive oxygen species (ROS), antioxidants, and nutrient status in primed and non-primed rice seedlings. Seeding were primed with distilled water, 60-µM selenium, or 100-mg L-1 salicylic acid. Results indicated that Pb toxicity did not affect the root growth, but severely reduced the shoot growth (length and biomass) of rice in N- or P-deprived seedlings. Rice seedlings grown with sufficient supply of nutrients or K-deprivation showed no growth reduction under Pb toxicity. Exposure of Pb stress triggered the production of ROS (H2O2, O2˙-, OH-) and lipid peroxidation rate particularly under N- or P-deprivation. Moreover, the shoot accumulations of macronutrients (P in particular) were also restricted under Pb toxicity. Seed priming treatments effectively alleviated the undesirable effects of Pb stress on rice growth. The primed rice seedlings showed minimal oxidative damage caused by excessive generation of ROS under Pb stress and/or nutrient deprivation. Seed priming strengthened the antioxidative defense system of rice seedlings by regulating the activities/levels of superoxide dismutase, catalase, peroxidase, and glutathione in rice leaves. Moreover, better accumulation of essential nutrients in primed rice seedlings prevented the excess uptake and translocation of Pb, as evident by the lowered shoot accumulation of Pb.

CRISPR/Cas9: the Jedi against the dark empire of diseases.

Advances in Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated system (CRISPR/Cas9) has dramatically reshaped our ability to edit genomes. The scientific community is using CRISPR/Cas9 for various biotechnological and medical purposes. One of its most important uses is developing potential therapeutic strategies against diseases. CRISPR/Cas9 based approaches have been increasingly applied to the treatment of human diseases like cancer, genetic, immunological and neurological disorders and viral diseases. These strategies using CRISPR/Cas9 are not only therapy oriented but can also be used for disease modeling as well, which in turn can lead to the improved understanding of mechanisms of various infectious and genetic diseases. In addition, CRISPR/Cas9 system can also be used as programmable antibiotics to kill the bacteria sequence specifically and therefore can bypass multidrug resistance. Furthermore, CRISPR/Cas9 based gene drive may also hold the potential to limit the spread of vector borne diseases. This bacterial and archaeal adaptive immune system might be a therapeutic answer to previous incurable diseases, of course rigorous testing is required to corroborate these claims. In this review, we provide an insight about the recent developments using CRISPR/Cas9 against various diseases with respect to disease modeling and treatment, and what future perspectives should be noted while using this technology.