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Aim: To map the glycaemic variabilities and insulin requirements across different phases of the menstrual cycle and assess the efficacy and performance of the MiniMed 780G system on mitigating glycaemic variabilities during phases of the menstrual cycle., Materials and Methods: A pilot study recruiting 15 adolescent and young adult females with type 1 diabetes was conducted. Only females with regular spontaneous menstruation were enrolled in the current study. Phases of each menstrual cycle were determined as either follicular phase or luteal phase. The study analysed continuous glucose monitoring metrics during two study periods: the open loop period (OLP) and the advanced hybrid closed-loop (AHCL) period; each period lasted 3 consecutive months., Results: During the OLP, the mean time in range (TIR) significantly decreased during the luteal phase compared with the follicular phase (65.13% ± 3.07% vs. 70.73% ± 2.05%) (P < .01). The mean time above range significantly increased from 21.07% ± 2.58% during the follicular phase to 24.87% ± 2.97% during the luteal phase (P < .01). After initiating the AHCL period, TIR was comparable during both phases of the menstrual cycle (P = .72), without increasing the time spent below 70 mg/dL (P > .05). Regarding insulin delivery during the AHCL period, the percentage of Auto basal and Auto correction delivered by the algorithm increased by 13.55% and 30.6%, respectively (P < .01), during the luteal phase., Conclusions: The fully automated adaptive algorithm of the MiniMed 780G system mitigated menstrual cycle-dependent glycaemic variability, successfully attaining the recommended glycaemic outcomes with a TIR greater than 70% throughout the entire menstrual cycle., (© 2024 John Wiley & Sons Ltd.)

Various thymol and carvacrol derivatives have been synthesized to test the anticancer activity potential. Computational methods including network pharmacology and molecular docking approaches were utilized to identify and assess the potential biological targets relating to cancer. Amongst the synthesized derivatives the ethoxy-cyclohexyl analogues were consistently the most active against a panel of 10 different cancer cell lines covering a variety of origins. Biological target predictions revealed the AKT1 protein to be a core and central target of the most active compounds. Molecular docking identified a binding pocket within this protein in which the most active compounds bind. The incorporation of computational analysis methods and conventional structure-activity approaches identified analogues of thymol and carvacrol with the highest anticancer potential, and analyzed their possible biological targets in a comprehensive manner., Competing Interests: There is no known financial or personal competing interest., (This journal is © The Royal Society of Chemistry.)

Oleuropein (OLP) is a naturally occurring phenolic compound in olive plant with antioxidant and anti-inflammatory potential and can possibly be used in treating pancreatic injuries. This investigation aimed to follow the molecular mechanism behind the potential therapeutic effect of OLP against pancreatic injury persuaded by ischemia-reperfusion (I/R). Pancreatic I/R injury was induced by splenic artery occlusion for 60 min followed by reperfusion. Oral administration of OLP (10 and 20 mg/kg) for 2 days significantly alleviated I/R-persuaded oxidative damage and inflammatory responses in pancreatic tissue as indicated by the decreased malondialdehyde (MDA) content and increased glutathione peroxidase (GPx) activity, accompanied by the suppression of myeloperoxidase (MPO) activity and reduced levels of interleukin-1beta (IL-1β), nuclear factor kappa B (NF-κB), and tumor necrosis factor alpha (TNF-α) in pancreatic tissues. Furthermore, OLP treatment markedly restored the serum levels of amylase, trypsinogen-activated peptide (TAP), and lipase, with concurrent improvement in pancreatic histopathological alterations. Moreover, treatment with OLP regulated the pancreatic expression of inducible nitric oxide synthase (iNOS) and high-mobility group box 1 (HMGB1) relative to rats of the pancreatic IR group. Thus, OLP treatment significantly alleviates the I/R-induced pancreatic injury by inhibiting oxidative stress and inflammation in rats through downregulation of HMGB1 and its downstream NF-κB signaling pathway.

HIV-1 integrase (IN), a major protein in the HIV life cycle responsible for integrating viral cDNA into the host DNA, represents a promising drug target. Small peptides have emerged as antiviral therapeutics for HIV because of their facile synthesis, highly selective nature, and fewer side effects. However, selecting the best candidates from a vast pool of peptides is a daunting task. In this study, multistep virtual screening was employed to identify potential peptides from a list of 280 HIV inhibitory peptides. Initially, 80 peptides were selected based on their minimum inhibitory concentrations (MIC). Then, molecular docking was performed to evaluate their binding scores compared to HIP000 and HIP00N which are experimentally validated HIV-1 integrase binding peptides that were used as a positive and negative control, respectively. The top-scoring docked complexes, namely, IN-HIP1113, IN-HIP1140, IN-HIP1142, IN-HIP678, IN-HIP776, and IN-HIP777, were subjected to initial 500 ns molecular dynamics (MD) simulations. Subsequently, HIP776, HIP777, and HIP1142 were selected for an in-depth mechanistic study of peptide interactions, with multiple simulations conducted for each complex spanning one microsecond. Independent simulations of the peptides, along with comparisons to the bound state, were performed to elucidate the conformational dynamics of the peptides. These peptides exhibit strong interactions with specific residues, as revealed by snapshot interaction analysis. Notably, LYS159, LYS156, VAL150, and GLU69 residues are prominently involved in these interactions. Additionally, residue-based binding free energy (BFE) calculations highlight the significance of HIS67, GLN148, GLN146, and SER147 residues within the binding pocket. Furthermore, the structure-activity relationship (SAR) analysis demonstrated that aromatic amino acids and the overall volume of peptides are the two major contributors to the docking scores. The best peptides will be validated experimentally by incorporating SAR properties, aiming to develop them as therapeutic agents and structural models for future peptide-based HIV-1 drug design, addressing the urgent need for effective HIV treatments., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The chemical profiles of both Zygophyllum album ( Z. album ) aerial parts and roots extracts were evaluated with LC-ESI-TOF-MS/MS analysis. Twenty-four compounds were detected. Among them, some are detected in both the aerial parts and the roots extracts, and others were detected in the aerial parts only. The detected compounds were mainly flavonoids, phenolic compounds, triterpenes and other miscellaneous compounds. Such compounds contribute to the diverse pharmacological activities elicited by the Z. album species. This study aimed to elucidate the antiepileptic effect of Z. album aerial parts and roots crude extracts against pentylenetetrazole (PTZ)-induced kindling in mice. Male albino mice were divided into four groups, eight animals each. All groups, except the control group, were kindled with PTZ (35 mg/kg i.p.), once every alternate day for a total of 15 injections. One group was left untreated (PTZ group). The remaining two groups were treated prior to PTZ injection with either Z. album aerial parts or roots crude extract (400 mg/kg, orally). Pretreatment with either extract significantly reduced the seizure scores, partially reversed the histological changes in the cerebral cortex and exerted antioxidant/anti-inflammatory efficacy evinced by elevated hippocampal total antioxidant capacity and SOD and catalase activities, parallel to the decrement in MDA content, iNOS activity and the TXNIB/NLRP3 axis with a subsequent decrease in caspase 1 activation and a release of IL-1β and IL-18. Moreover, both Z. album extracts suppressed neuronal apoptosis via upregulating Bcl-2 expression and downregulating that of Bax, indicating their neuroprotective and antiepileptic potential. Importantly, the aerial parts extract elicited much more antiepileptic potential than the roots extract did.

Objective: To evaluate efficacy and safety of either or both silodosin and mirabegron as MET for distal ureteric stones ≤ 10 mm., Patients and Methods: This study enrolled a total of 105 patients, aged between 20 and 56 years, diagnosed by single radiopaque distal ureteral stone measuring ≤ 10 mm. The recruitment period spanned from May 2020 to December 2021. The patients were randomly divided into three groups, with each group consisting of 35 participants. Group A received a once-daily dose of 8 mg of silodosin, group B received a once-daily dose of 50 mg of mirabegron, and group C received a combination of both medications. Treatment was administered to all patients until the stone was expelled or for a maximum duration of four weeks. The stone-free rate was determined by analyzing KUB films with or without ultrasonography., Results: The rate of stone expulsion was significantly higher in group C compared to groups A and B (P = 0.04 and P = 0.004, respectively). The mean (standard deviation) time for stone expulsion in groups A, B, and C was 14 ± 2.3 days, 11 ± 3.1 days, and 7 ± 2.2 days, respectively. Group C demonstrated a significantly shorter stone expulsion time compared to groups A and B (P = 0.001 and P = 0.04, respectively). The frequency of renal colic in group C was significantly lower than that in groups A and B, resulting in a reduced requirement for analgesics (P < 0.05). Anejaculation occurred at a significantly higher rate in the silodosin group (73.9%) and combination group (84%) compared to the mirabegron group (P < 0.05)., Conclusions: The findings of this study suggest that both silodosin and mirabegron are effective treatments for the expulsion of lower ureteric stones. Furthermore, the combination of these medications leads to an increased rate of stone expulsion and a reduced duration of expulsion., (© 2023. The Author(s).)

Total extract of Tephrosia purpurea ( T. purpurea ) expressed potent ex-vivo bronchodilator effect in isolated Guinea pigs' tracheal muscles. Fractionation of T. purpurea total extract ( TPTE) using liquid-liquid technique followed by ex-vivo bronchodilator testing indicated that the activity was trapped to the chloroform (CHCl 3 ) soluble fraction. Phytochemical study of the CHCl 3 fraction guided by ex-vivo bronchodilator activity led to the isolation of 7 active flavones of which compounds 1 ( epi- Tephroapollin G), 3 (Acetyltephroapollin C), 4 (4''-Dehydroxytephroapollin E), and 5 ( epi- Tephroapollin F) were new. Structures were identified using relevant spectroscopic tools including optical rotations and CD data. Compounds 1 , 3 , 4 and lanceolatin A ( 6 ) behaved like papaverine by inhibiting carbachol (CCh) as well as high potassium (K + )-mediated contractions at equivalent concentrations with varied potencies whereas (-)-Tephroapollin G ( 2 ) selectively inhibited CCh-mediated contractions but was not found active against high K + . epi -Tephroapollin F ( 5 ) and (-)-Pseudosemiglabrin ( 7 ) in contrast were significantly more potent to abolish CCh induced contraction when compared with high K + similar to dicyclomine. Papaverine like dual phosphodiesterase enzyme Ca ++ ion inhibitory activities of 1, 3, 4 and 6 were confirmed indirectly by the bolster of the isoprenaline curves against CCh to the left whereas Ca ++ inhibitory effect of 1 and 3 - 7 was confirmed by the rightward deflection of Ca ++ concentration-response curves (CRCs) towards right with quashing of the maximum response in same fashion like verapamil. Moreover, compounds 2, 5 and 7 at lower concentrations showed selective blockade of muscarinic receptor similar to atropine. Oral administration of the TPTE , CHCl 3 and 7 to guinea pigs significantly protected against bronchospasm induced by 0.2 % histamine aerosol in vivo ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V. on behalf of King Saud University.)

Cannabis sativa is one of the oldest plants utilized by humans for both economic and medical purposes. Although the use of cannabis started millennia ago in the Eastern hemisphere, its use has moved and flourished in the Western nations in more recent centuries. C. sativa is the source of psychoactive cannabinoids that are consumed as recreational drugs worldwide. The C21 aromatic hydrocarbons are restricted in their natural occurrence to cannabis (with a few exceptions). Delta-9-tetrahydrocannabinol (Δ 9 -THC) is the main psychoactive component in cannabis, with many pharmacological effects and various approved medical applications. However, a wide range of side effects are associated with the use of Δ 9 -THC, limiting its medical use. In 1966, another psychoactive cannabinoid, Delta-8-tetrahydrocannabinol (Δ 8 -THC) was isolated from marijuana grown in Maryland but in very low yield. Δ 8 -THC is gaining increased popularity due to its better stability and easier synthetic manufacturing procedures compared to Δ 9 -THC. The passing of the U.S. Farm Bill in 2018 led to an increase in the sale of Δ 8 -THC in the United States. The marketed products contain Δ 8 -THC from synthetic sources. In this review, methods of extraction, purification, and structure elucidation of Δ 8 -THC will be presented. The issue of whether Δ 8 -THC is a natural compound or an artifact will be discussed, and the different strategies for its chemical synthesis will be presented. Δ 8 -THC of synthetic origin is expected to contain some impurities due to residual amounts of starting materials and reagents, as well as side products of the reactions. The various methods of analysis and detection of impurities present in the marketed products will be discussed. The pharmacological effects of Δ 8 -THC, including its interaction with CB1 and CB2 cannabinoid receptors in comparison with Δ 9 -THC, will be reviewed.

Inflammatory responses and oxidative stress contribute to the pathogenesis of brain ischemia/reperfusion (IR) injury. Naturally occurring bioflavonoids possess antioxidant and anti-inflammatory properties. The phytochemicals of Juniperus sabina L. , known as "Abhal" in Saudi Arabia, have been studied and cupressuflavone (CUP) has been isolated as the major bioflavonoid. This study aimed to investigate the neuroprotective potential of CUP in reducing brain IR damage in rats and to understand probable mechanisms. After 60 min of inducing cerebral ischemia by closing the left common carotid artery (CCA), blood flow was restored to allow reperfusion. The same surgical procedure was performed on sham-operated control rats, excluding cerebral IR. CUP or vehicle was given orally to rats for 3 days prior to ischemia induction and for a further 3 days following reperfusion. Based on the findings of this study, compared to the IR control group, CUP-administered group demonstrated reduced neurological deficits, improved motor coordination, balance, and locomotor activity. Additionally, brain homogenates of IR rats showed a decrease in malondialdehyde (MDA) level, an increase in reduced glutathione (GSH) content, and an increase in catalase (CAT) enzyme activity following CUP treatment. CUP suppressed neuro-inflammation via reducing serum inflammatory cytokine levels, particularly those of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) and enhancing the inflammatory cytokine levels, such as Nuclear factor kappa- B (NF-κB), TANK-binding kinase-1 (TBK1), and interferon beta (IFN-β) in brain tissues. Furthermore, CUP ameliorated the histological alterations in the brain tissues of IR rats. CUP significantly suppressed caspase-3 expression and downregulated the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway as a result of suppressing High mobility group box 1 (HMGB1). To our knowledge, this is the first study to document the neuroprotective properties of CUP. Thus, the study findings revealed that CUP ameliorates IR-induced cerebral injury possibly by enhancing brain antioxidant contents, reducing serum inflammatory cytokine levels, potentiating the brain contents of TBK1 and IFN-β and suppressing the HMGB1/TLR-4 signaling pathway. Hence, CUP may serve as a potential preventive and therapeutic alternative for cerebral stroke., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)