Context: Thymol and carvacrol are components of many essential oils known to exert smooth muscle relaxation. Aims: To evaluate the relaxant effect of thymol, carvacrol, and their acetate derivatives on isolated tracheal and penile corpus cavernosum smooth muscles of guinea pigs, assess aphrodisiac activity in rats, and explore the potential biological targets via network pharmacology and molecular docking. Methods: Organ bath experiments were conducted to assess ex vivo relaxant effect, while in vivo aphrodisiac activity was evaluated in rats by monitoring mount latency, mount frequency, intromission latency, intromission frequency, and ejaculation latency. Computational methods were used to predict pharmacokinetic and physicochemical properties, as well as potential gene targets for the compounds. Molecular docking was performed to study interactions with BK potassium channels, which were suspected to mediate the relaxant effects. Results: Thymol acetate produced the most relaxant effect on bronchial and penial muscles, followed by thymol, carvacrol acetate, and then carvacrol. Iberiotoxin prevented this relaxant effect, confirming the involvement of potassium channels. Administration of thymol and thymol acetate to rats significantly improved all aphrodisiac parameters. Computational analysis revealed a high number of gene targets, including potassium channels. Molecular docking revealed the acetylated variants to bind to a modulatory interface within BK potassium channels. Furthermore, binding was similar to a known allosteric channel activator. Conclusions: Acetylation of thymol enhanced its bronchodilator, erectogenic, and aphrodisiac activities. Computational analysis suggests interaction with genes encoding potassium channel domains. Molecular docking identified a modulatory pocket within BK potassium channels in which the acetylated analogues bind similarly to a reference ligand.

Introduction:Ischemia/reperfusion (I/R) injury is a critical complication associated with pancreatic surgery, and transplantation, which frequently develops into acute pancreatitis due to increased oxidative stress and inflammatory cascades. Aim:This study aimed to assess the protective effects of vulgarin (VLG) and epivulgarin (EPV) against pancreatic I/R- injury in rats. Methods:Rats were given oral dosages of 10 or 20 mg/kg of VLG or EPV for two days prior to I/R and 24 h after reperfusion. Pancreatic I/R was induced by occluding the pancreatic blood supply for 60 minutes followed by reperfusion. Key biochemical markers including serum amylase, lipase, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), and glutathione peroxidase (GPx) were measured. Additionally, pancreatic tissue expression of high mobility group box 1 (HMGB1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was assessed via immunohistochemistry. Results:Pancreatic I/R significantly elevated serum levels of amylase (4.5-fold) and lipase (5.8-fold), oxidative stress marker; MDA (8.5-fold), as well as pro-inflammatory cytokines; TNF-α (10.4-fold) and IL-1β (5.6-fold) compared to controls (p≤0.01). The antioxidant GPx activity was suppressed by 84% (p≤0.05). Treatment with VLG and EPV dose-dependently attenuated these changes, with the highest dose of EPV reducing serum amylase by 72% and MDA by 76% compared to untreated I/R rats (p≤0.01). Immunohistochemical analysis revealed marked downregulation of HMGB1 and NF-κB expression in VLG and EPV-treated groups. High-dose therapies showed near normalization of numerous biochemical and molecular parameters. Conclusion:Vulgarin and epivulgarin exhibited significant protective effects against pancreatic I/R injury by reducing oxidative stress and suppressing HMGB1/NF-κB-mediated inflammatory signaling. These findings suggest the therapeutic potential of VLG and EPV in managing acute pancreatitis and related pancreatic injuries.

Context: Alopecia affects a large population and current treatments have limited efficacy and tolerability. Essential oils have gained increasing interest as natural, low-risk alternatives. Aims: To evaluate the effects of Syzygium aromaticum and Rosmarinus officinalis oils, alone and in combination, on hair regrowth in rats and compared with 2% minoxidil. Methods: S. aromaticum oil was prepared by hydro-distillation, while R. officinalis oil was purchased from the local market and analysed by GCMS. Male Wistar rats (n=30) were randomized to negative control (vehicle), 2% minoxidil, S. aromaticum oil, R. officinalis oil, and a S. aromaticum-R. officinalis oil mixture groups. Treatments were applied topically on a shaved dorsal skin area once a day for 35 days. The times required for hair growth initiation and completion were recorded, along with hair growth scores on days 7, 21, and 35. On day 35, hair weight, length, and thickness were measured, and skin histology was examined. Results: All active treatments showed significant improvements in hair regrowth parameters manifested by a significant reduction in the duration of hair initiation and completion and improvement in all the measured parameters. The effects of S. aromaticum oil and R. officinalis oil on hair re-growth were comparable to that of minoxidil. The oils mixture demonstrated superior performance to minoxidil in terms of faster regrowth initiation (6.5 days), completion (21.83 days), and higher hair weight (22.2 mg/cm²) and length (16.67 mm). Histology indicated a higher follicle density in treated groups. Conclusions: The oils mixture exhibited an additive effect, outperforming minoxidil in promoting hair regrowth.

Erectile dysfunction is a common condition affecting a significant percentage of males worldwide. Thymol is a natural compound found in the essential oil of thyme and several other plant species, and it exhibits various biological activities. The objective of this study was to prepare a thymol formulation (THY-K17) and evaluate its relaxant effect on isolated guinea pig corpus cavernosum smooth muscle (CCSM) as well as its aphrodisiac effect in rats. THY-K17 was successfully prepared using Kollidon® 17 PF as the polymeric carrier and mannitol as a diluent. Thymol was transformed into an amorphous state, which was confirmed by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). More than 90

The journal retracts the article titled “Design and Evaluation of Solid Lipid Nanoparticles Loaded Topical Gels: Repurpose of Fluoxetine in Diabetic Wound Healing” [...]

Salmonella enterica is a clinically significant oro-fecal pathogen that causes a wide variety of illnesses and can lead to epidemics. S. enterica expresses a lot of virulence factors that enhance its pathogenesis in host. For instance, S. enterica employs a type three secretion system (T3SS) to translocate a wide array of effector proteins that could change the surrounding niche ensuring suitable conditions for the thrive of Salmonella infection. Many antimicrobials have been recently introduced to overcome the annoying bacterial resistance to antibiotics. Enoxacin is member of the second-generation quinolones that possesses a considerable activity against S. enterica. The present study aimed to evaluate the effect of enoxacin at sub-minimum inhibitory concentration (sub-MIC) on S. enterica virulence capability and pathogenesis in host. Enoxacin at sub-MIC significantly diminished both Salmonella invasion and intracellular replication within the host cells. The observed inhibitory effect of enoxacin on S. enterica internalization could be attributed to its ability to interfere with translocation of the T3SS effector proteins. These results were further confirmed by the finding that enoxacin at sub-MIC down-regulated the expression of the genes encoding for T3SS-type II (T3SS-II). Moreover, enoxacin at sub-MIC lessened bacterial adhesion to abiotic surface and biofilm formation which indicates a potential anti-virulence activity. Importantly, in vivo results showed a significant ability of enoxacin to protect mice against S. enterica infection and decreased bacterial colonization within animal tissues. In nutshell, current findings shed light on an additional mechanism of enoxacin at sub-MIC by interfering with Salmonella intracellular replication. The outcomes presented herein could be further invested in conquering bacterial resistance and open the door for additional effective clinical applications.

Ischemia-reperfusion (IR) injury is a major cause of multiple organ failure. The purpose of this study was to look into the role of Tephrosia purpurea (TEP) and its active constituent pseudosemiglabrin (PS) in alleviating severe acute pancreatitis and its associated acute lung injury. We established a rat pancreatic IR model, and the rats were treated with TEP (200 mg/kg and 400 mg/kg) and PS (20 and 40 mg/kg), in addition to the IR control and sham groups. The results showed that the respiratory parameters, including inspiratory time (Ti), expiratory time (Te), duration (Dr), and respiratory rate (RR), were comparable among all groups, while peak inspiratory flow (PIF), forced vital capacity (FVC), and forced expiratory volume at 0.1 s (FEV0.1) were significantly impaired. Notably, PS at 40 mg/kg showed normal PIF, FVC, and FEV0.1/FVC compared to the IR group, indicating an improved lung function. Additionally, TEP and PS showed protective effects on pancreatic and lung tissues compared to the IR control group, with the following effects: alleviating pathological damage; reducing serum levels of trypsinogen activation peptide (TAP), lipase, and amylase; decreasing oxidative stress markers such as MDA and MPO; restoring antioxidant enzyme activity (GPx); suppressing inflammatory markers TNF-α, IL-6, and NF-κB; downregulating HMGB1 gene in pancreatic tissue; and upregulating the IL-22 gene in lung tissues. In conclusion, the obtained findings demonstrate that oral supplementation of TEP and PS to rats with pancreatic IR alleviates pancreatic and lung injuries by reducing oxidative stress and modulating inflammatory processes, which offers an attractive therapeutic option for severe acute pancreatitis and its associated acute lung injury.

Ferula assa-foetida known as Asafoetida has a long-established history in folk medicine as a therapeutically useful drug in many disorders. The current paper explored the in vivo and in vitro anti-inflammatory activities of the plant. Liquid ethanol crude extract was subjected to liquid-to-liquid extraction, and the fractions so obtained were evaluated against the carrageenan-induced acute paw edema model in rats, to determine the anti-inflammatory effects. The fractions that gave the greatest activity-ethyl acetate and hexane- afforded four sesquiterpene coumarins: auraptene (1), umbelliprenin (2), galbanic acid (3), and kamolonol (4). The overall structure was determined through detailed spectroscopic investigation, 1H NMR, 13C NMR, DPET135, COSY, HSQC, HMBC, HRESIMS, and other references to the literature. Evaluation of the in vitro activity of the LPS stimulated RAW 264.7 macrophages showed that the compound 4 (ethyl acetate fraction) exhibited maximum inhibitory action against the generation of nitric oxide (NO), followed by the compounds 1 and 2 of the hexane fraction. Network Pharmacology, Molecular Docking and Molecular dynamic simulation analysis were used to identify the target genes and explain the potential differences between the active compounds. As far as the authors know, there are no earlier reports that mention the anti-inflammatory action of kamolonol (4).

Flavonoids have recently been shown to be useful to people suffering from vascular disorders caused by a high-fat diet (HFD). The flavonoid rutin (RT) exhibits numerous pharmacological effects, including antioxidant, cytoprotective, vasoprotective, and cardioprotective activities. The primary objective of this research was to assess the efficacy of RT against obesity-related vascular endothelial dysfunction (VED) in rats fed HFD. A total of 24 mature Wistar rats were blindly categorized into 4 treatment and control groups: normal control, obese control, and obese which were given RT at 50 and 100 mg/kg for the final 3 weeks of the experimental period. Animals' body mass and food consumption have been estimated periodically. In addition, liver mass and retroperitoneal fat mass per body mass, abdominal circumference (AC), LEE index, and body mass index (BMI) were estimated. Moreover, lipid profile parameters were assessed in serum. The effect on vascular endothelium reactivity was investigated in an isolated rat aorta. A histopathological investigation of the aorta was performed. The obese control group exhibited higher body, liver, and retroperitoneal fat weights. Significantly, RT intake reverses all these alterations. Furthermore, RT decreased food intake, AC, Lee index, and BMI in HFD-fed rats. The lipid profile of HFD-fed rats was also improved after RT treatment, with lower triglycerides, total cholesterol, LDL-C, and VLDL-C levels and higher HDL-C levels in the serum of HFD-fed rats. Through the ex-vivo investigation, RT groups showed improved vascular endothelium function in HFD-fed animals compared to the obese control group. Taking together, RT could be a promising option for preventing obesity-associated VED.

Introduction: Androgenetic alopecia (AGA) is a multifactorial and age-related dermatological disease that affects both males and females, usually at older ages. Traditional hair repair drugs exemplified by minoxidil have limitations such as skin irritation and hypertrichosis. Thus, attention has been shifted to the use of repurposing drugs. Metformin is an anti-diabetic drug, that can promote hair follicle regeneration via upregulation of the hair-inductive capability. Hence, the current study aims to fabricate a safe and effective nanoemulsion to improve metformin efficacy in targeting AGA. Methods: Rosemary oil was selected as the oily phase due to its ability to increase blood flow and hair growth. Rosemary-based nanoemulsions were statistically optimized by Box-Behnken experimental design, loaded with metformin, and incorporated into a hydrogel to form a nanoemulgel. Metformin-loaded nanoemulsions were assessed for their diametric size, uniformity, zeta potential, and metformin characteristics within the formulated nanosystem. The nanoemulgel was then evaluated in terms of its pH, percentage drug content, and in-vitro release performance. In-vivo study assessed the nanoemulgel's ability to augment hair growth in rats. Results: The experimental design displayed that using 50%w/w, 20%w/w, and 10%w/w of Cremophor (R), Labrafil (R), and deionized water, respectively, resulted in nanoemulsion formulation with the smallest globule size (125.01 +/- 0.534 nm), unimodal size distribution (PDI=0.103), negative surface charge (-19.9 +/- 2.01 mV) with a spherical morphological structure. Rosemary-based nanoemulgel displayed acceptable physicochemical characterizations namely; a neutral pH value of 6.7 +/- 0.15, high drug content (92.9 +/- 2.3%), and controlled metformin in-vitro release. Besides, the formulated nanoemulgel significantly increased the number of hair follicles in the animal model compared with other controls and tested groups. Conclusion: The designed nanoemulgel is a promising approach for treating androgenic alopecia.

Ferula assa-foetida known as Asafoetida has a long-established history in folk medicine as a therapeutically useful drug in many disorders. The current paper explored the in vivo and in vitro anti-inflammatory activities of the plant. Liquid ethanol crude extract was subjected to liquid-to-liquid extraction, and the fractions so obtained were evaluated against the carrageenan-induced acute paw edema model in rats, to determine the anti-inflammatory effects. The fractions that gave the greatest activity-ethyl acetate and hexane- afforded four sesquiterpene coumarins: auraptene ( 1 ), umbelliprenin ( 2 ), galbanic acid ( 3 ), and kamolonol ( 4 ). The overall structure was determined through detailed spectroscopic investigation, 1 H NMR, 13 C NMR, DPET135, COSY, HSQC, HMBC, HRESIMS, and other references to the literature. Evaluation of the in vitro activity of the LPS stimulated RAW 264.7 macrophages showed that the compound 4 (ethyl acetate fraction) exhibited maximum inhibitory action against the generation of nitric oxide (NO), followed by the compounds 1 and 2 of the hexane fraction. Internet Pharmacology, Molecular Docking and Molecular dynamic simulation analysis were used to identify the target genes and explain the potential differences between the active compounds. As far as the authors know, there are no earlier reports that mention the anti-inflammatory action of kamolonol ( 4 ).

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.

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 (CHCl3) soluble fraction. Phytochemical study of the CHCl3 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, CHCl3 and 7 to guinea pigs significantly protected against bronchospasm induced by 0.2 % histamine aerosol in vivo.

Surveys indicated that stroke classified among the leading cause of death as well as combined death and disability worldwide resulting in a great loss for the global economy. The present study aims to evaluate the neuroprotective potential of the biflavonoid amentoflavone (AMNT) in alleviating cerebral ischemia/reperfusion (IR) injury in rats, and to elucidate the possible underlying mechanism of an experimental condition with similar circumstances to stroke. Cerebral ischemia was achieved through left common carotid artery occlusion for 60 min, followed by blood flow restoration. Sham-operated control rats subjected to the same surgical process except for brain IR. Rats were orally administered AMNT/ or vehicle for three days’ prior surgical operation, and for another three days after left brain IR. Rats of all groups were assessed for neurological deficits 24 h following brain IR. Each group was divided into two subgroups one for the rotarod testing and biochemical assessment while the other subgroup to perform the activity cage testing, histopathological study, immunohistochemistry, and gene expression analysis. AMNT enhanced brain levels of GSH and CAT activities, suppressed neuroinflammation via reducing the inflammatory cytokines in the serum, and enhanced brain contents of TBK1 and IFNβ. AMNT downregulated TLR4-/NF-κB signaling pathway as a result of the HMGB1 suppression. Moreover, AMNT blocked apoptotic cell death by suppressing the NF-κB signaling pathway and reducing the activation of caspase-3. These findings revealed that AMNT attenuates I/R–induced cerebral injury possibly by regulating the HMGB1-mediated TLR4/NF-kB pathway. Thus, AMNT could provide potential preventive and therapeutic option for cerebral stroke.

BackgroundRatio of neonatal intensive care unit (NICU) admission by respiratory distress syndrome (RDS) as a part of total NICU admission is increasing yearly with the highest increase in RDS incidence in extreme preterm neonates.Lung ultrasound (LUS) can be used in diagnosis of RDS complication with better detection, compared to Chest X-ray, of consolidation and sub-pleural atelectasis.It can be used also in follow up and early assessment of the response to surfactant replacement therapy. AimAssess the response to early selective replacement therapy in premature neonates using lung ultrasonography and predict need for second dose of surfactant replacement therapy using lung ultrasonography. Patients /MethodsNeonates ≤ 34 weeks (60 neonates) was enrolled in this study and treated with early continuous positive airway pressure (CPAP).LUS was performed in the first 2 hours of postnatal life.16 neonates treated with surfactant replacement therapy according to European consensus guidelines 2019 update.LUS was repeated after surfactant administration within 2 hours.7 neonates needed second dose of surfactant if the oxygen requirements remained high ≥10 hours (the expected half-life of surfactant) after first dose administration. ResultsOur study shows that LUS score pre surfactant at a cut off value of ≥ 10 has a sensitivity of 85.7 % and specificity of 77.8 % for prediction of surfactant retreatment.LUS score post surfactant at a cut off value of ≥ 6 has a sensitivity of 85.7 % and specificity of 88.9 %. ConclusionLung ultrasound score is useful in assessment of the response to early selective surfactant therapy in preterm neonate and predict need for second dose of surfactant therapy.

The polar fractions of the Juniperus species are rich in bioflavonoid contents. Phytochemical study of the polar fraction of Juniperus sabina aerial parts resulted in the isolation of cupressuflavone (CPF) as the major component in addition to another two bioflavonoids, amentoflavone and robustaflavone. Biflavonoids have various biological activities, such as antioxidant, anti-inflammatory, antibacterial, antiviral, hypoglycemic, neuroprotective, and antipsychotic effects. Previous studies have shown that the metabolism and elimination of biflavonoids in rats are fast, and their oral bioavailability is very low. One of the methods to improve the bioavailability of drugs is to alter the route of administration. Recently, nose-to-brain drug delivery has emerged as a reliable method to bypass the blood–brain barrier and treat neurological disorders. To find the most effective CPF formulation for reaching the brain, three different CPF formulations (A, B and C) were prepared as self-emulsifying drug delivery systems (SEDDS). The formulations were administered via the intranasal (IN) route and their effect on the spontaneous motor activity in addition to motor coordination and balance of rats was observed using the activity cage and rotarod, respectively. Moreover, pharmacokinetic investigation was used to determine the blood concentrations of the best formulation after 12 h. of the IN dose. The results showed that formulations B and C, but not A, decreased the locomotor activity and balance of rats. Formula C at IN dose of 5 mg/kg expressed the strongest effect on the tested animals.

The total alcohol extract obtained from the aerial parts of R. stricta and fractions of the liquid–liquid fractionation process were tested against picornavirus-causing foot-and-mouth disease (FMD) based on the traditional use of the plant in Saudi Arabia. The most active petroleum ether soluble fraction was subjected to chromatographic purification, and nine compounds were isolated, identified using various chemical and spectroscopic methods, and tested for their anti-viral potential. The new ester identified as α-Amyrin 3-(3′R-hydroxy)-hexadecanoate (1) was the most active compound with 51% inhibition of the viral growth and was given the name Rhazyin A. Compounds with ursane skeleton were more active than those with lupane skeleton except in the case of the acid derivatives where betulenic acid showed 26.1% inhibition against the viral growth, while ursolic acid showed only 16.6% inhibition. Moreover, molecular docking analysis using a glide extra-precision module was utilized for investigating the possible molecular interactions accounting for anti-viral activity against picornavirus of the nine isolated compounds. Molecular docking studies revealed a strong binding of the discovered hits within the active site of FMDV 3Cpro. Compound 1 showed the lowest docking score within the nine isolated compounds comparable to the two known anti-viral drugs; glycyrrhizic acid and ribavirin. The results of this research will provide lead candidates from natural origin with potential safety and efficacy compared to the synthetic ones with lower production costs for managing FMVD.

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.

The purpose of this study was to evaluate the effectiveness of samarcandin (SMR) in preventing testicular injury caused by ischemia/reperfusion (I/R) in rats. Rats were divided into 4 groups at random: the sham group, the T/D control group (CONT), the T/D group receiving SMR treatment at 10 mg/kg (SMR-10), and the T/D group receiving SMR treatment at 20 mg/kg (SMR-20). When compared to the CONT group, SMR improved the oxidant/antioxidant balance by reducing malondialdehyde (MDA), nitric oxide (NOx), and increasing reduced glutathione (GSH), gluta-thione peroxide (GSH-Px), and superoxide dismutase (SOD). Moreover, SMR increased the levels of the steroid hormones’ testosterone (TST), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in the blood as well as controlled the inflammatory mediators; interleukin-6 (IL6), tumor necrosis factor alpha (TNF-α), and nuclear factor κB (NF-κB). Nevertheless, SMR-treated animals showed a considerable downregulation of the apoptotic marker caspase-3. The T/D-induced histopathological changes were reduced and Proliferating Cell Nuclear Antigen (PCNA) protein expression was enhanced by SMR. These effects are associated with upregulation of testicular (Nuclear factor erythroid 2-related factor 2 (Nrf2), Heme oxygenase-1 (HO-1), and downregulation of NF-κB mRNA expression levels. These findings suggest that SMR may be able to prevent T/D-induced testis damage by mainly regulating the expression of Nrf2 and NF-B, which seems to mediate its promising antioxidant, anti-inflammatory and antiapoptotic effects seen in this study.

BackgroundRespiratory distress syndrome (RDS) continues to represent a crucial problem for preterm neonates despite the new advancement in its management.Currently, management of RDS is mainly through using early continuous positive airway pressure (CPAP) in the management of preterm neonates since birth together with early selective administration of surfactant.Lung ultrasound (LUS), as a simple and non-invasive diagnostic technique with no exposure to ionizing radiation, can be used as a reliable diagnostic tool for diagnosis of neonatal respiratory distress syndrome with good sensitivity and specificity. AimAssess the applicability of lung ultrasonography for early prediction of the surfactant need in preterm neonates ≤ 34 weeks treated with CPAP. Patients /MethodsWe studied 60 neonates ≤ 34 weeks treated with early CPAP; LUS was done in the first 2 hours of life.16 neonates received surfactant therapy according to European guidelines 2019 update.We assess reliability of LUS score for prediction of surfactant treatment. ResultsThe result of our study shows that in the group received surfactant the median LUS score was 10, While in the group didn't need surfactant therapy the median LUS score was 4.About reliability of LUS score for prediction of surfactant treatment.Our results showed that LUS score at a cut off value of ≥ 6 has a sensitivity of 93.8 % and specificity of 84.1 %.while Chest X ray score at a cut off value of ≥ 5 has a sensitivity of 81.3 % and specificity of 77.3 %. ConclusionLUS score is a useful tool in early prediction of need for surfactant administration in preterm neonates on CPAP.