The Therapeutic Potency of Silver/Chitosan, Silver/Saponin and Chitosan/ Saponin Nanocomposites on Ethanol-induced Gastric Ulcers in Wistar Rats.

BACKGROUND: The annual incidence of peptic ulcer disease is estimated to be four million cases worldwide, with an average lifetime risk of 7.5% in individuals of all ages. Polymer nanocomposites have novel prospects in the field of modern medicine. OBJECTIVE: The present research endeavors to assess the therapeutic efficacy of nanoparticles composed of silver/chitosan, silver/saponin, and chitosan/saponin against gastric ulcers induced by ethanol in Wistar rats. METHODS: Forty-eight rats were randomly split into eight groups of the same size. Oral ethanol (5 ml/kg of body weight) was given to all rat groups except the control one for 1 hour before treatment. Control and ulcer groups of rats were given distilled water orally. The rats in the other groups were given orally 1/10 LD50 of each treatment as follows: AgNPs, chitosan NPs, Saponin, AgNPs-Chitosan NPs, AgNP-Saponin, and chitosan-Saponin NPs. RESULTS: NP-treated groups showed a significant increase in the gastric juice pH, glutathione reduced, catalase, and nitric oxide while gastric juice volume, ulcer index, and malondialdehyde levels decreased compared with the ulcer group. Histopathological investigation of stomach showed improvement in NPs groups specially in the chitosan-Saponin NPs group. CONCLUSION: The current study revealed that silver-chitosan, silver-saponin and chitosansaponin nanocomposites effectively treat gastric ulcers. Chitosan-Saponin nanoparticles showed high therapeutic effectiveness against gastric ulcer in rats.

Immediate effect of physical activity on the autonomic nervous system in individuals with autism spectrum disorders of different age groups: a randomised trial.

Background: Autism spectrum disorder (ASD) is one of the most complex neurodevelopmental disorders. It affects almost all human physiological systems. Individuals with ASD often display dysregulation in their autonomic nervous system (ANS), which may elicit differing effects across age groups. Also, studying the ANS missed several important parameters related to ANS. Studying the ANS is crucial in developing adaptive behavioural strategies and maintaining communication abilities and social behaviours. Thus, this study compared the immediate effect of physical activity on the ANS in individuals with ASD in different age groups. Methods: 200 participants (106 males and 94 females) took part in a double-blinded randomised design. All participants were divided into four groups according to their age (4-7, 7-10, 10-13 and 14-18 years old). Participants performed a 60 min treadmill walk. The main outcome measurements were heart rate (HR), saturation of peripheral oxygen (SpO2), respiratory rate (RR) and end-tidal carbon dioxide (etCO2). Results: Before the study, there were non-significant differences between groups in their physical characteristics (body mass index, Childhood Autism Rating Scale, physical activity level, both parents' existence, aerobic capacity and gender) (p>0.05). At baseline measurements, there were non-significant differences between all groups for all outcome measurements (p>0.05). Immediately after physical activity, there was significant difference between group 1 and other groups (p<0.05), while all other differences were non-significant (p>0.05). At the follow-up (after 15 min of rest), group 1 maintained significant differences with the other groups for all outcome measurements (p<0.05), while there were non-significant differences between the other three groups (p>0.05). Conclusion: This study revealed that the SpO2 significantly decreased immediately after the physical activity, while HR, RR and etCO2 significantly increased immediately after physical activity in comparison to the baseline measurements. Contrary to other ANS parameters (SpO2, RR and etCO2), HR in early ages (4-7 years old) was higher after physical activity and remained elevated longer than other ages. The early ages (4-7 years old) take more time to return to the normal status of ANS parameters including SpO2, HR, RR and etCO2. Trial registration number: NCT05725733.

ß-glucan mitigates ovalbumin-induced airway inflammation by preventing oxidative stress and CD8+ T cell infiltration.

BACKGROUND: Bronchial asthma is a severe respiratory condition characterized by airway inflammation, remodeling, and oxidative stress. ß-Glucan (BG) is a polysaccharide found in fungal cell walls with powerful immunomodulatory properties. This study examined and clarified the mechanisms behind BG's ameliorativeactivitiesin an allergic asthma animal model. METHOD: BG was extracted from Chaga mushroom and characterized using FT-IR, UV-visible, zeta potential, and 1H NMR analysis. The mice were divided into five groups, including control, untreated asthmatic, dexamethasone (Dexa)-treated (1 mg/kg), and BG (30 and 100 mg/kg)-treated groups. RESULTS: BG treatment reduced nasal scratching behavior, airway-infiltrating inflammatory cells, and serum levels of IgE significantly. Additionally, BG attenuated oxidative stress biomarkers by lowering malonaldehyde (MDA) concentrations and increasing the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT). Immunohistochemical and flow cytometric analyses have confirmed the suppressive effect of BG on the percentage of airway-infiltrating cytotoxic CD8+ T cells. CONCLUSION: The findings revealed the role of CD8+ T cells in the pathogenesis of asthma and the role of BG as a potential therapeutic agent for asthma management through the suppression of airway inflammation and oxidative stress.

Determining if the prognostic nutritional index can predict outcomes in community acquired bacterial pneumonia.

BACKGROUND: The Prognostic Nutritional Index (PNI) uses albumin levels and total lymphocyte count to predict the relationship between immune-nutritional state and prognosis in a variety of diseases, however it has not been studied in community acquired bacterial pneumonia (CABP). We conducted a historical cohort study to determine if there was an association between PNI and clinical outcomes in patients with CABP. METHODS: We reviewed 204 adult patients with confirmed CABP, and calculated admission PNI and Neutrophil-to-Lymphocyte Ratio (NLR). A comparative analysis was performed to determine the association of these values, as well as other risk factors, with the primary outcomes of 30-day readmissions and death. RESULTS: Of the 204 patients, 56.9% (116) were male, 48% (98) were black/African American and the mean age was 63.2 ± 16.1 years. The NLR was neither associated with death nor 30-day readmission. The mean PNI in those who survived was 34.7 ± 4.5, compared to 30.1 ± 6.5, in those who died, p < 0.001. From multivariable analysis after controlling for the Charlson score and age, every one-unit increase in the PNI decreased the risk of death by 13.6%. The PNI was not associated with readmissions. CONCLUSIONS: These findings suggest that poor immune and nutritional states, as reflected by PNI, both contribute to mortality, with a significant negative correlation between PNI and death in CABP. PNI was predictive of mortality in this patient cohort; NLR was not. Monitoring of albumin and lymphocyte count in CABP can provide a means for prevention and early intervention.

Correction: Anthelmintic and therapeutic effects of the biogenic zinc oxide nanoparticles against acute kidney injury induced by Parascaris equorum Infection in rats.

[This corrects the article DOI: 10.1007/s12639-023-01637-z.].

Anthelmintic and therapeutic effects of the biogenic zinc oxide nanoparticles against acute kidney injury induced by Parascaris equorum Infection in rats.

Complications of parasite infections, especially kidney disease, have been linked to poorer outcomes. Acute kidney damage, glomerulonephritis, and tubular dysfunction are the most prevalent renal consequences of Parascaris equorum infection. The purpose of this study was to determine the pharmacological effects of green-produced zinc oxide nanoparticles (ZnO NPs) on P. equorum infection in male Wistar rats. Thirty-six male rats were divided into two groups of 18 each: infected and non-infected. Both groups were separated into three subgroups, each of which received distilled water, 30 mg/kg ZnO NPs, and 60 mg/kg ZnO NPs. After 10 days of ZnO NPs administration, four larvae per gram of kidney tissue were present in the untreated infected group. While, no larvae were present in ZnO NPs (30 mg/kg) treated group, and one larva/g.tissue was present in ZnO NPs (60 mg/kg) treated group compared to untreated infected animals. P. equorum infected rats had increased kidney biomarkers (creatinine, urea, uric acid), malondialdehyde, and nitric oxide, with a significant decrease in their antioxidant systems. On the other hand, infected treated rats with green-produced zinc oxide nanoparticles had a substantial drop in creatinine, urea, uric acid, malondialdehyde, and nitric oxide, as well as a significant rise in their antioxidant systems. P. equorum infection in rats caused severe degenerative and necrotic renal tissues. On the other hand, there were no detectable histopathological alterations in rats treated with ZnO NPs (30, 60 mg/kg) as compared to the infected untreated animals. When compared to infected untreated mice, immunohistochemical examination of nuclear factor-kappa B showed a significant decrease during treatment with ZnO NPs (30, 60 mg/kg). Green-produced zinc oxide nanoparticles are a viable therapeutic strategy for Parascaris equorum infection due to their potent anthelmintic activity, including a significant decrease in larval burden in infected treated rats.

Echinochrome exhibits anti-asthmatic activity through the suppression of airway inflammation, oxidative stress, and histopathological alterations in ovalbumin-induced asthma in BALB/c mice.

Asthma is a chronic pulmonary disease with marked infiltrating inflammatory cells and reduced respiratory performance. Echinochrome (Ech) is a dark-red pigment isolated from the sea urchin spines, shells, and ova. It has antioxidant, antimicrobial, and anti-inflammatory properties, but whether it can be used in asthma treatment has yet to be investigated. In this research, we aimed to study the inhibitory actions of Ech on allergic asthma symptoms in mice. Mice were divided into 4 groups (n = 8 for each): control, ovalbumin-challenged, and Ech-treated (0.1 and 1 mg/kg). At the end of the experiment, nasal scratching, lung oxidative stress, airway inflammation, and remodeling were assessed. In ovalbumin-challenged BALB/C mice, treatment with Ech significantly decreased nasal scratching, lung oxidative stress, inflammatory cell infiltration, mucus hyperproduction and hyperplasia of goblet cells, IgE levels, and inflammatory cytokines. It also inhibited NF-κB phosphorylation. This is the first study to investigate the immunomodulatory effect of Ech against allergic asthma in mice. According to our findings, we imply that Ech may be utilized as a treatment for allergic asthma.

Anthelmintic and Hepatoprotective Activities of the Green-Synthesized Zinc Oxide Nanoparticles Against Parascaris equorum Infection in Rats.

MAIN CONCLUSIONS: Green-synthesized zinc oxide nanoparticle is a promising treatment modality against parasitic infection through its powerful anthelmintic, antioxidant, healing promotion, and anti-inflammation effects. BACKGROUND: Nanoparticles have many properties, depending on their size, shape, and morphology, allowing them to interact with microorganisms, plants, and animals. OBJECTIVES: Investigation of the therapeutic effects of green-synthesized zinc oxide nanoparticles (ZnO NPs) on Parascaris equorum infection in rats. METHODS: Thirty-six rats were divided into two divisions: the first division is noninfected groups were allocated into three groups. Group 1: Control, group 2: ZnO NPs (30 mg/kg), and group 3: ZnO NPs (60 mg/kg). The second division is infected groups were allocated into three groups. Group 1: vehicle, group 2: ZnO NPs (30 mg/kg), and group 3: ZnO NPs (60 mg/kg). FINDINGS: Ten days post-infection, two larvae per gram of liver tissue were present in the vehicle group compared to the control group. No larvae were recovered from ZnO NPs (30 mg/kg), and one larva/g.tissue from ZnO NPs (60 mg/kg)-treated groups compared to untreated infected animals. Green-synthesized ZnO NPs caused a significant decrease in liver functions, low-density lipoprotein (LDL), cholesterol, triglycerides, malondialdehyde (MDA), and nitric oxide (NO). While it caused a significant increase in hemoglobin (HB), high-density lipoprotein (HDL), butyrylcholinesterase (BCHE), glutathione (GSH), catalase (CAT), and glutathione S-transferase (GST) in infected treated rats. The histological inflammation and fibroplasia scores showed a significant enhancement during the treatment with ZnO NPs (30, 60 mg/kg) compared to the infected untreated animals that scored the highest pathological destruction score. Immunohistochemical markers of NF-κB showed a significant decrease during the treatment with ZnO NPs (30, 60 mg/kg) compared to the infected untreated animals.

Hematopoietic effect of echinochrome on phenylhydrazine-induced hemolytic anemia in rats.

Background: Hemolytic anemia (HA) is a serious health condition resulting from reduced erythrocytes' average life span. Echinochrome (Ech) is a dark-red pigment found in shells and spines of sea urchins. Aim: Studying the potential therapeutic effect of Ech on phenylhydrazine (PHZ)-induced HA in rats. Methods: Eighteen rats were divided into three groups (n = 6): the control group, the phenylhydrazine-induced HA group and the Ech group, injected intraperitoneally with PHZ and supplemented with oral Ech daily for 6 days. Results: Ech resulted in a considerable increase in RBCs, WBCs, and platelets counts, hemoglobin, reduced glutathione, catalase, and glutathione-S-transferase levels, and a significant decrease in aspartate & alanine aminotransferases, alkaline phosphatase, gamma-glutamyl transferase, bilirubin, creatinine, urea, urate, malondialdehyde & nitric oxide levels in anemic rats. Histopathological examination of liver and kidney tissue samples showed marked improvement. Conclusion: Ech ameliorated phenylhydrazine-induced HA with a hepatorenal protective effect owing to its anti-inflammatory and antioxidant properties.

New nicotinamide derivatives as potential anticancer agents targeting VEGFR-2: design, synthesis, in vitro, and in silico studies.

Herin, new nicotinamide candidates were designed and synthesized as VEGFR-2 inhibitors. In vitro antiproliferative activities were assessed against MCF-7, HepG-2 and HCT-116 cancer cell lines. The top cytotoxic members 15a, 15b, 16, 18a, and 18b were estimated against their selected target (VEGFR-2). Further mechanistic tests were studied for the most potent cytotoxic candidate 18a, these studies revealed the ability of compound 18a to hinder the progression of HCT-116 cells at S and Pre-G1phases besides boosting early and late apoptosis. Also compound 18a was found to significantly decrease the levels immunomodulatory proteins TNF-α and IL-6 while showing a four-fold rise in an apoptotic marker caspase-3 when compared to control cells. The therapeutic index of the designed derivatives was evaluated by computational ADMET and toxicity calculations as well as their potentiality to occupy the VEGFR-2 active site was signposted by molecular docking assessments. Finally, molecular dynamic simulation studies of compound 18a-VEGFR-2 complex indicated the high steadiness of compound 18a in the VEGFR-2 active site. This study presents compound 18a as a lead candidate that can be optimized to get a strong VEGFR-2 inhibitor.Communicated by Ramaswamy H. Sarma.

Role of Enhancing Aerobic Capacity in Countering COVID-19-induced Liver Injury in Elderlies.

COVID-19 is still a world disaster; however, its vaccination is globally available. Liver and gastrointestinal disturbances occur in patients infected with COVID-19 at varying incidences. Aging decreases the functions of the liver. Thus, the elderly have a weaker response to the COVID-19 virus. The COVID-19 virus affects the liver directly through direct and indirect mechanisms. It directly affects the renin-angiotensin system or indirectly causes sepsis, uncontrolled immune reactions, drug-related hepatic injury, and cytokine storm. Also, COVID-19 vaccines and anti-drugs have adverse effects on the liver too. Thus, this review explores the effect of enhancing aerobic capacity as a nonpharmacological intervention on decreasing COVID- 19-induced liver injury. Enhancing aerobic capacity decreases COVID-19-induced liver injury through the following: 1) downregulating systemic and tissue ACE/ANG II/AT1R axis, upregulating ACE2/ANG 1-7/Mas axis, and moving the renin-angiotensin system to the direction of the ACE2/ANG (1-7)/Mas axis, 2) Improving mitochondrial function and oxygenation to body and lung tissues, causing a decrease in harmful oxidative reactions, 3) Increasing the processing of accumulated free radicals and inhibiting the acute respiratory distress syndrome, 4) Acting as an antioxidant to protect the liver from oxidative stress, 5) Increasing the effect of antiviral drugs and COVID-19 vaccines, which improves the function of immune biomarkers, decreases the viral load, and increases the body's defense against the virus, 6) Decreasing coagulation abnormalities and thrombosis. In conclusion, enhancing aerobic capacity may be an efficient nonpharmacological intervention to decrease COVID-19-induced liver injury in elderlies and regenerate the liver to its normal status after being infected by the COVID-19 virus. It also helps to strengthen the body's immunity for better effects of both COVID-19 vaccination and drugs.

Recent Advances in Floating Photovoltaic Systems.

In recent years, floating photovoltaic (FPV) technologies have gained more importance as a key source of clean energy, particularly in the context of providing sustainable energy to buildings. The rise of land scarcity and the need to reduce carbon emissions have made FPV systems a cost-effective solution for generating electricity. This review article aims to explore the rapidly growing trend of floating PV systems, which can be a practical solution for regions with limited land areas. The article discusses the structure of the PV modules used in FPV plants and key factors that affect site suitability choice. Moreover, the article presents various techniques for cooling and cleaning FPV to keep optimal performance and discusses feasible trends and prospects for the technology. Finally, this paper proposes the potential integration of FPV systems with other technologies to enhance energy generation efficiency and discusses other research aimed at the advancement of the technology. By examining the various features of FPV systems, this review article contributes to understanding the advantages and challenges associated with using this sustainable energy technology in different regional contexts.

The role of creatine kinase in distinguishing generalized tonic-clonic seizures from psychogenic non-epileptic seizures (PNES) and syncope: a retrospective study and meta-analysis of 1300 patients.

BACKGROUND/AIM: As the clinical differentiation between epileptic seizures, psychogenic non-epileptic seizures (PNES), and syncope depends mainly on a detailed report of the event, which may not be available, an objective assessment of a potential biochemical analysis is needed. We aimed to investigate whether serum creatine kinase (CK) could be used to differentiate epileptic seizure from PNES and syncope and to assess the strength of evidence present. METHODS: We directed a retrospective cohort study coupled with a systematic review and meta-analysis of studies that measured CK in patients with epilepsy, PNES, syncope, and healthy controls. RESULTS: The cohort study, which traced 202 patients, showed that the CK level was significantly higher 48 h after the event in the epilepsy group versus patients with syncope (p < 0.01) Along with 1086 patients obtained through a database search for meta-analysis, CK level compared to different types of seizures from PNES was higher in epileptic seizure patients with a mean difference of 568.966 mIU/ml (95% CI 166.864, 971.067). The subgroup analysis of CK showed that it was higher in GTCS compared to syncope with a mean difference of 125.39 mIU/ml (95% CI 45.25, 205.52). DISCUSSION: Increased serum levels of CK have been associated mainly with epileptic seizures in relation to non-epileptic events. However, further studies would try to explore the variation in measurements and any other potential diagnostic marker. CONCLUSION: The cohort study shows that the CK level in epilepsy seizures is higher after 48 h from the event compared to syncope. Moreover, the meta-analysis results show the present diagnostic utility of CK and its importance to be used in accordance with a detailed report of the event.

PreOperative Planning for Adult Spinal Deformity Goals: Level Selection and Alignment Goals.

Adult Spinal Deformity (ASD) is a complex pathologic condition with significant impact on quality of life, including pain, loss of function, and fatigue. Achieving realignment goals is crucial for long-term results. Reliable preoperative planning strategies, including nomograms, measurement tools, and level selection, are key to maximizing the likelihood of achieving a good outcome following ASD corrective surgery. This review covers recent literature on such strategies, including review of the different targets for realignment and their association with outcomes (both patients-reported outcomes and complications), selection of upper and lower instrumented vertebrae, and the latest innovation in preoperative planning for deformity surgery.

Evaluation of the Therapeutic Effect of Curcumin-Conjugated Zinc Oxide Nanoparticles on Reserpine-Induced Depression in Wistar Rats.

Depression, a devastating brain illness, necessitates the exploration of novel antidepressant treatments. We evaluated the antidepressant effects of free curcumin, zinc oxide nanoparticles (ZnO NPs), and curcumin-conjugated zinc oxide nanoparticles (Zn(cur)O NPs). The nanoformulations were extensively characterized using advanced techniques. An acute toxicity study ensured the safety of Zn(cur)O NPs. Rats were assigned to one of five groups: control, reserpine-induced depression model, treatment with ZnO NPs, free curcumin, or Zn(cur)O NPs. Behavioral assessments (forced swimming test [FST] and open-field test [OFT]) and neurochemical analyses were conducted. Zn(cur)O NPs exhibited superior efficacy in ameliorating reserpine-induced behavioral and neurochemical effects compared to free curcumin and ZnO NPs. The reserpine-induced model displayed reduced motor activity, swimming time, and increased immobility time in the FST and OFT. Treatment with Zn(cur)O NPs 45 mg/kg significantly improved motor activity and reduced immobility time. Furthermore, Zn(cur)O NPs decreased malondialdehyde (MDA) levels while increasing reduced glutathione (GSH) and catalase (CAT) levels. Additionally, concentrations of serotonin (5-HT) and norepinephrine (NE) increased. In conclusion, curcumin-conjugated zinc oxide nanoparticles demonstrate potent antidepressant effects, alleviating depressive-like behavior in rats. These findings support Zn(cur)O NPs as a promising therapeutic strategy for depression management, warranting further investigation and clinical validation.

ß1-adrenergic receptor polymorphisms: a possible genetic predictor of bisoprolol response in acute coronary syndrome.

Aim: To investigate the association between beta1-adrenergic receptor (ADRB1) polymorphisms and response to bisoprolol treatment in beta-blocker naive patients with acute coronary syndrome (ACS). Patients & methods: Seventy-seven patients received bisoprolol for four weeks. Blood pressure and heart rate were measured at baseline and during treatment. TaqMan allelic discrimination method was utilized for ADRB1 Ser49Gly and Arg389Gly genotyping. Results: Arg389Arg carriers showed greater reductions in systolic and diastolic blood pressure (-8.5% ± 7.8% vs -0.76% ± 8.7%, p = 0.000218), and (-9.5% ± 9.7% vs -0.80% ± 11.5%, p = 0.000149), respectively, compared with Gly389 carriers. No statistical difference was found for study's outcomes based on codon 49. Conclusion: Arg389Gly polymorphism is a promising bisoprolol response predictor in ACS patients.

Pharmacogenetics is a field of study that explores how our genes can affect how well certain medicines work. In this study, scientists looked at a specific gene called beta1-adrenergic receptor to see how it can influence a drug called bisoprolol. They wanted to find out if some people's genes made bisoprolol work better for them. They studied 77 patients with a heart problem called acute coronary syndrome (ACS) who were taking bisoprolol for 4 weeks. The researchers discovered that people with a particular gene piece called Arg389Arg responded better to bisoprolol. They had bigger reductions in their blood pressure compared with those who had a different gene called Gly389. This finding suggests that by looking at a person's genes, doctors might be able to predict how well bisoprolol will work for them. This way, doctors can choose the best treatment for each patient, making sure they get the most benefit from the medicine.

Echinochrome Ameliorates Physiological, Immunological, and Histopathological Alterations Induced by Ovalbumin in Asthmatic Mice by Modulating the Keap1/Nrf2 Signaling Pathway.

Asthma is a persistent inflammatory disease of the bronchi characterized by oxidative stress, airway remodeling, and inflammation. Echinochrome (Ech) is a dark-red pigment with antioxidant and anti-inflammatory activities. In this research, we aimed to investigate the effects of Ech against asthma-induced inflammation, oxidative stress, and histopathological alterations in the spleen, liver, and kidney in mice. Mice were divided into four groups (n = 8 for each): control, asthmatic, and asthmatic mice treated intraperitoneally with 0.1 and 1 mg/kg of Ech. In vitro, findings confirmed the antioxidant and anti-inflammatory activities of Ech. Ech showed antiasthmatic effects by lowering the serum levels of immunoglobulin E (IgE), interleukin 4 (IL-4), and interleukin 1ß (IL-1ß). It attenuated oxidative stress by lowering malondialdehyde (MDA) and nitric oxide (NO) contents and increasing reduced glutathione (GSH), superoxide dismutase (SOD), glutathione-s-transferase (GST), and catalase (CAT) in the liver, spleen, and kidney. Moreover, it protected asthma-induced kidney and liver functions by increasing total protein and albumin and decreasing aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, urea, and uric acid levels. Additionally, it ameliorated histopathological abnormalities in the lung, liver, spleen, and kidney. Additionally, molecular docking studies were used to examine the interactions between Ech and Kelch-like ECH-associated protein 1 (Keap1). PCR and Western blot analyses confirmed the association of Ech with Keap1 and, consequently, the regulatory role of Ech in the Keap1-(nuclear factor erythroid 2-related factor 2) Nrf2 signaling pathway in the liver, spleen, and kidney. According to our findings, Ech prevented asthma and its complications in the spleen, liver, and kidney. Inhibition of inflammation and oxidative stress are two of echinochrome's therapeutic actions in managing asthma by modulating the Keap1/Nrf2 signaling pathway.

Placenta percreta in primigravida with unscarred uterus complicated by uterine rupture and sudden maternal and fetal death: an autopsy case report.

Placenta percreta is a rare, aggressive, and severe form of the placenta accreta spectrum. One of its most devastating effects is the sudden rupture of uterus. Uterine scarring is the leading risk factor for uterine rupture, although it can also happen, but rarely, in an unscarred uterus showing more severe repercussions. The present study reported a case of an Egyptian primigravida female, aged 29 years old, at 32 weeks of gestation who died suddenly due to uterine rupture complicating placenta percreta, the diagnosis of which was first settled during autopsy. There was no history of abdominal trauma. No medical history of significance was present. Autopsy denoted an intrauterine fetal death of 32 weeks gestational age. The fundus of the uterus had a laceration (rupture) of the uterine wall including the serosa and myometrium. The placenta has extensively infiltrated the fundus uterine wall and penetrated the myometrium and serosa. Histopathological examination of the ruptured site on the uterus confirms total invasion of the uterine wall by chorionic villi with the presence of hemorrhage and fibrin indicating placenta percreta. Uterine rupture due to placenta percreta may go unnoticed, especially when no associated high-risk factors exist. The current case depicts that placenta percreta is a rare but critical complication of pregnancy that may exist at any stage of pregnancy without any associated high-risk factors with unusual symptoms and leads to uterine rupture and sudden death.

Design, Synthesis, and Biological Evaluation of New Potential Unusual Modified Anticancer Immunomodulators for Possible Non-Teratogenic Quinazoline-Based Thalidomide Analogs.

Sixteen new thalidomide analogs were synthesized. The new candidates showed potent in vitro antiproliferative activities against three human cancer cell lines, namely hepatocellular carcinoma (HepG-2), prostate cancer (PC3), and breast cancer (MCF-7). It was found that compounds XII, XIIIa, XIIIb, XIIIc, XIIId, XIVa, XIVb, and XIVc showed IC50 values ranging from 2.03 to 13.39 µg/mL, exhibiting higher activities than thalidomide against all tested cancer cell lines. Compound XIIIa was the most potent candidate, with an IC50 of 2.03 ± 0.11, 2.51 ± 0.2, and 0.82 ± 0.02 µg/mL compared to 11.26 ± 0.54, 14.58 ± 0.57, and 16.87 ± 0.7 µg/mL for thalidomide against HepG-2, PC3, and MCF-7 cells, respectively. Furthermore, compound XIVc reduced the expression of NFκB P65 levels in HepG-2 cells from 278.1 pg/mL to 63.1 pg/mL compared to 110.5 pg/mL for thalidomide. Moreover, compound XIVc induced an eightfold increase in caspase-8 levels with a simultaneous decrease in TNF-α and VEGF levels in HepG-2 cells. Additionally, compound XIVc induced apoptosis and cell cycle arrest. Our results reveal that the new candidates are potential anticancer candidates, particularly XIIIa and XIVc. Consequently, they should be considered for further evaluation for the development of new anticancer drugs.

Design, synthesis, in silico studies, and biological evaluation of novel pyrimidine-5-carbonitrile derivatives as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers.

A novel series of pyrimidine-5-carbonitrile derivatives bearing benzylidene and hydrazone moieties with different linkers (spacers) were designed and synthesized as possible inhibitors of the vascular endothelial growth factor receptor-2 (VEGFR-2). The newly synthesized compounds were evaluated in vitro for their cytotoxic activities against two human cancer cell lines namely colon cancer (HCT-116) and breast cancer (MCF-7) using sorafenib as a standard anticancer drug. Compounds 9d, 11e, 12b, and 12d showed higher cytotoxic activities than sorafenib with IC50 values ranging from 1.14 to 10.33 µM. In particular, compound 11e exhibited excellent activities against HCT-116 and MCF-7 with IC50 values of 1.14 and 1.54 µM, respectively. Moreover, compound 11e exhibited about 47.32-fold cytotoxic activity against normal human fibroblast (WI-38) cells, lower than the cytotoxicity against the cancer cells. Compounds 11e and 12b were the most potent VEGFR-2 inhibitors with IC50 values of 0.61 and 0.53 µM, respectively, compared to sorafenib. Bedsides, compound 11e arrested the HCT-116 cell growth at S and sub-G1 phases, induced a significant increase in the apoptotic cells, and caused remarkable decrease in the levels of TNF-α, IL-6, and caspase-3. Finally, the binding patterns of the target derivatives were investigated through the docking study against the proposed molecular target (VEGFR-2, PDB ID 1YWN). The results of molecular docking studies showed similar binding modes to sorafenib against VEGFR-2. In addition, molecular dynamic simulations revealed the stability of compound 11e in the active site for 100 ns.