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Purpose Current therapies for osteoarthritis (OA) are limited to analgesics and anti-inflammatory drugs. Considering the importance of oxidative stress and inflammatory mediators in OA etiology, we tested the hypothesis that targeting the renin–angiotensin–aldosterone system (RAAS) can improve OA anomalies. Diminazene (DIZE), an activator of angiotensin-converting enzyme 2 and the angiotensin 2 type-1 receptor blocker losartan (LOS) were used for this purpose. Methods OA was induced by a single intra-articular injection of monosodium iodoacetate. The effects of exposure to DIZE or LOS for 21 days on OA anomalies in rats’ knees were investigated. Evaluation of motor function, nociception, and inflammatory response was done using rotarod, knee bend and knee swelling tests. Markers of knee joint inflammation, and cellular oxidation in addition to the RAAS biomarkers, were assessed in knee tissues, along with radiological and histopathological investigations. Results Elevations in inflammatory and oxidative markers in knee tissues of OA rats were mostly improved by the two therapeutic drugs. Such effect was also reflected in the rotarod, knee bend and knee swelling tests. Treatment with DIZE has shown a more prominent effect than LOS in controlling OA-associated inflammation and cellular oxidation. Markers of RAAS have also shown better responsiveness to DIZE over LOS. Conclusions DIZE has shown a prominent increase in the angiotensin 1–7 amount, highlighting the involvement of the signaling pathway in the immunomodulatory effect. The radiological and histopathology examination came to confirm the outcome of biochemical markers, nominating diminazene aceturate as a possible therapeutic option for OA. Graphical Abstract

The implication of the tissue-localized renin-angiotensin system (RAS) in the pathogenesis of osteoarthritis (OA) has been documented in the last decades. A combination of intraarticular (IA) corticosteroid and hyaluronic acid (HYAL) is approved for pain relief in patients with mild to moderate OA. Combining HYAL with an activator of angiotensin-converting enzyme 2, diminazen aceturate (DIZE), was evaluated in this study for its therapeutic potential. Monosodium iodoacetate was used to induce OA. The effects of daily administration of DIZE versus once-per-week IA injection of HYAL and a combination of both drugs for 21 days on OA deformities in rats’ knees were observed. Evaluation of motor activities, pain, and inflammatory response was done using rotarod, knee bend, and knee swelling tests. RAS components, inflammatory biomarkers, and oxidative stress mediators were measured in the knee joint. X-ray radiological examination and histopathological investigations were used to assess joint degeneration and regeneration. Levels of both inflammatory and oxidative markers in knee joint homogenate of OA rats rose, and these increments were mostly improved by the three therapies with a more prominent effect of the drug combination, an effect that was also reflected in the behavioral tests. RAS markers have shown better responsiveness to the combination therapy over both drugs individually, showing a pronounced increase in the angiotensin 1–7 amount. Both radiological and histopathology investigations came to confirm the biochemical results, nominating a combination of HYAL and DIZE as a possible therapeutic option for OA.

Morbidity and mortality risks are enhanced in preeclamptic (PE) mothers and their offspring. Here, we asked if sexual dimorphism exists in (i) cardiovascular and renal damage evolved in offspring of PE mothers, and (ii) offspring responsiveness to antenatal therapies. PE was induced by administering N G -nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day, oral gavage) to pregnant rats for 7 days starting from gestational day 14. Three therapies were co-administered orally with L-NAME, atrasentan (endothelin ETA receptor antagonist), terutroban (thromboxane A2 receptor antagonist, TXA2), or α-methyldopa (α-MD, central sympatholytic drug). Cardiovascular and renal profiles were assessed in 3-month-old offspring. Compared with offspring of non-PE rats, PE offspring exhibited elevated systolic blood pressure and proteinuria and reduced heart rate and creatinine clearance (CrCl). Apart from a greater bradycardia in male offspring, similar PE effects were noted in male and female offspring. While terutroban, atrasentan, or α-MD partially and similarly blunted the PE-evoked changes in CrCl and proteinuria, terutroban was the only drug that virtually abolished PE hypertension. Rises in cardiorenal inflammatory (tumor necrosis factor alpha, TNFα) and oxidative (isoprostane) markers were mostly and equally eliminated by all therapies in the two sexes, except for a greater dampening action of atrasentan, compared with α-MD, on tissue TNFα in female offspring only. Histopathologically, antenatal terutroban or atrasentan was more effective than α-MD in rectifying cardiac structural damage, myofiber separation, and cytoplasmic alterations, in PE offspring. The repair by antenatal terutroban or atrasentan of cardiovascular and renal anomalies in PE offspring is mostly sex-independent and surpasses the protection offered by α-MD, the conventional PE therapy.

Antitumor therapeutic strategies that fundamentally rely on the induction of DNA damage to eradicate and inhibit the growth of cancer cells are integral approaches to cancer therapy. Although DNA-damaging therapies advance the battle with cancer, resistance, and recurrence following treatment are common. Thus, searching for vulnerabilities that facilitate the action of DNA-damaging agents by sensitizing cancer cells is an active research area. Therefore, it is crucial to decipher the detailed molecular events involved in DNA damage responses (DDRs) to DNA-damaging agents in cancer. The tumor suppressor p53 is active at the hub of the DDR. Researchers have identified an increasing number of genes regulated by p53 transcriptional functions that have been shown to be critical direct or indirect mediators of cell fate, cell cycle regulation, and DNA repair. Posttranslational modifications (PTMs) primarily orchestrate and direct the activity of p53 in response to DNA damage. Many molecules mediating PTMs on p53 have been identified. The anticancer potential realized by targeting these molecules has been shown through experiments and clinical trials to sensitize cancer cells to DNA-damaging agents. This review briefly acknowledges the complexity of DDR pathways/networks. We specifically focus on p53 regulators, protein kinases, and E3/E4 ubiquitin ligases and their anticancer potential. Cancer therapy: Responses to DNA damage The tumor suppressor protein p53 is at the center of a network of cellular proteins that coordinate responses to DNA damage, and a deeper understanding of this network could reveal new targets for cancer therapy. Commonly called the ‘guardian of the genome’, p53 helps determine whether cells initiate repairs or self-destruct in response to genomic disruption. Mutations affecting p53 play a critical role in determining tumor response to therapy. Researchers led by Roger Leng at the University of Alberta, Edmonton, Canada, have reviewed the various proteins and pathways that interact with p53, and thus inform its ‘decision-making’ process. The development of drugs that affect p53 directly has proven a huge challenge, but these interacting proteins and pathways could offer therapeutic targets. The authors highlight vulnerabilities that could render tumors more susceptible to radiation or chemotherapy.

Solid state nuclear magnetic resonance (ssNMR) is a powerful and attractive characterization method for obtaining insights into the chemical structure and dynamics of a wide range of materials. Current interest in cellulose-based materials, as sustainable and renewable natural polymer products, requires deep investigation and analysis of the chemical structure, molecular packing, end chain motion, functional modification, and solvent–matrix interactions, which strongly dictate the final product properties and tailor their end applications. In comparison to other spectroscopic techniques, on an atomic level, ssNMR is considered more advanced, especially in the structural analysis of cellulose-based materials; however, due to a dearth in the availability of a broad range of pulse sequences, and time consuming experiments, its capabilities are underestimated. This critical review article presents the comprehensive and up-to-date work done using ssNMR, including the most advanced NMR strategies used to overcome and resolve the structural difficulties present in different types of cellulose-based materials.

In this study, the hydrolysis of TiCl 4 was utilized to synthesize titanium dioxide clusters (TiO 2 NCs) at a sub-nanometer scale. Precise control over the synthesis process resulted in the production of stable particles with well-defined size distributions. These TiO 2 NCs were specifically developed to facilitate the conversion of SO x into organo-sulfonic acid derivatives under visible light irradiation. Various characterization techniques such as TEM, EDX, XRD, UV–Vis-DRS, Raman, and FTIR were employed to analyze the formed photocatalysts, including TiO 2 nanoparticles (NPs) and NCs. The efficiency of catalytic SO x removal depended significantly on the particle size and surface area of the nanocatalysts, as well as the presence of thymol or naphthol ( 1,2) . These materials ( 1,2) proved to be highly effective in removing SO x from flue gas under ambient conditions, specifically at room temperature. The conversion of thymol or naphthol involved a combination of adsorption and catalytic oxidation–reduction reactions. This photocatalytic approach for SO x conversion offers several advantages, including high performance, elimination of the need for high temperature or pressure, and rapid catalytic removal within a short reaction time of 10 min. TiO 2 NCs demonstrate high efficiency in SO x removal, offering a promising solution for pollution control. Unlike some other methods, TiO 2 nanoparticles can be potentially regenerated and reused, making them a more sustainable approach.

The aim of the current study was to develop a novel triphenylaniline-based porous organic polymer (TPABPOP-1) by the Friedel–Crafts reaction for the efficient elimination of Pb(II) from an aqueous environment. XPS, FTIR, SEM, TGA, and 13C CP/MAS NMR analyses were applied to characterize the synthesized TPABPOP-1 polymer. The BET surface area of the TPABPOP-1 polymer was found to be 1290 m2/g. FTIR and XPS techniques proved the uptake of Pb(II) was successfully adsorbed onto TPABPOP-1. Using batch methods, Pb(II) ion adsorption on the TPABPOP-1 was studied at different equilibrium times, pH values, initial Pb(II) concentration, adsorption mass, and temperature. The outcomes exhibited that the optimum parameters were t: 180 min, m: 0.02 g, pH: 5, T: 308 K, and [Pb(II)]: 200 mg/L. Nonlinear isotherms and kinetics models were investigated. The Langmuir isotherm model suggested that the uptake of Pb(II) was favorable on the homogeneous surface of TPABPOP-1. Adsorption kinetics showed that the PFO model was followed. Pb(II) removal mechanisms of TPABPOP-1 may include surface adsorption and electrostatic attraction. The uptake capacity for Pb(II) was identified to be 472.20 mg/g. Thermodynamic factors exhibited that the uptake of Pb(II) was endothermic and spontaneous in standard conditions. Finally, this study provides effective triphenylaniline-based porous organic polymers (TPABPOP-1) as a promising adsorbent with high uptake capacity.

Type 2 Diabetes mellitus is a major public health concern with an alarming global growth rate. According to the World Health Organization (WHO), Saudi Arabia ranks seventh in the world and second in the Middle East for the largest estimated burden of diabetic cases. Evidence shows that pharmacist-led care programs can be beneficial for the effective treatment of diabetes mellitus. Current study was aimed to evaluate the impact of Pharmacist-Based Diabetic Intervention (PDIM) for Type 2 Diabetes patients on knowledge of the disease, adherence to medications and self-care practices during the first wave of COVID-19. A multi-arm pre-post study was conducted among type 2 diabetic patients from April to October 2021 in Sakaka, Saudi Arabia. Patients were randomly divided into an intervention and a control group. The intervention group received the PDIM, whereas the control group only received the usual care. The pharmacist-based diabetes intervention model consisted of a diabetic educational module and medication improvement strategies. Furthermore, the intervention group also received specific telepharmacy services (calls, messages or emails) to address their medication-related problems, inquire about medication adherence and follow-up. At the end of six months, disease knowledge, self-care practices, and medication adherence score were analyzed. Furthermore, HbA1c and lipid profile were also compared. A total of 109 patients were included in the study. A significant difference was observed in the knowledge score between the intervention and control group (16.89 ± 2.01 versus 15.24 ± 2.03, p-value < 0.001). Similarly, self-care practices also improved in the intervention group as compared to the control group (4.39 ± 1.10 versus 3.16 ± 0.97, p-value < 0.001). Furthermore, the medication adherence and HbA1c significantly improved during between the group analysis (p < 0.05). Our study demonstrates that pharmacist-based diabetes intervention model is effective in improving patients’ knowledge of diabetes, self-care practices, medication adherence and glycemic control.

The p53 tumor suppressor protein plays a crucial role in detecting and eliminating various oncogenic threats by promoting processes such as cell cycle arrest, DNA repair, senescence, and apoptosis. UBE4B is essential for negatively regulating p53 during normal conditions and following DNA damage. In previous studies, we demonstrated that UBE4B targets phosphorylated p53 for degradation in response to DNA damage. However, the regulation of UBE4B in relation to DNA damage in cancer is not well understood. In this study, we show that the UBE4B protein is regulated through a phosphorylation and dephosphorylation mechanism in response to DNA damage. Phosphorylation of UBE4B reduces its binding affinity to p53, leading to an accumulation of p53 in the cell. Wip1 plays a crucial role in the dephosphorylation of UBE4B, which stabilizes the activity of the UBE4B protein in response to DNA damage. UBE4B is primarily phosphorylated through ATR-mediated signaling, which reduces its binding affinity with p53, resulting in the accumulation and activation of p53. When Wip1 is inhibited, there is a significant increase in UBE4B phosphorylation, leading to more p53 accumulation and a reduction in cell growth. Therefore, understanding how UBE4B is regulated in cancer cells in response to DNA-damaging agents could help develop new therapeutic strategies to improve the prognosis for cancer patients.

This study is an attempt to explore war-related trauma, its stressful effects, and the coping strategies of Saudi schoolchildren. The authors hypothesized that children exposed to war-related trauma will show higher levels of PTSD, and that those with higher levels of PTSD symptoms use more maladaptive coping strategies. The study describes the correlation between traumatic events and posttraumatic stress disorder (PTSD) as well as coping strategies. Five hundred twenty-seven intermediate and high school students, 12 to 18 years old, living in the conflict zone in southern Saudi Arabia completed three standardized self-reported scales: the War Zone Traumatic Events Checklist, the Child PTSD Symptom Scale, and the Children’s Coping Strategies Checklist. Each participating student was randomly chosen. Analysis was based on two groups: the high-PTSD symptoms group (182 children) and the low-PTSD symptoms group (345 children). The study was conducted between September 2020 and April 2022 while the war was ongoing as part of an ongoing larger study. Children exposed to war-related traumatic events exhibited greater prevalence rates for PTSD. The children reported high levels of PTSD symptoms and applied a variety of coping strategies to manage related stress. Participants rarely reported that psychological or educational interventions had been used to manage the war-related traumatic experiences and PTSD or to improve related coping styles. The results are discussed in the context of mental health services needed for children in the conflict zone. To bridge the gap between health care services and the needs of children with PTSD, and for better understanding and interventions, health professionals are invited to develop a biopsychosocial model that identifies the risks of PTSD related to exposure to war-related traumatic events in school-aged children and, hence, provide a multidisciplinary intervention program that educates, encourages, and supports teachers and parents in following medical recommendations and goals.