Hedgehog signaling mastery: R51211's promise in augmenting the therapeutic efficacy of sorafenib.

Sorafenib is a multikinase inhibitor employed for managing hepatocellular carcinoma (HCC). The emergence of sorafenib resistance presents an obstacle to its therapeutic efficacy. One notable approach to overcoming sorafenib resistance is the exploration of combination therapies. The role of hedgehog signaling in sorafenib resistance has been also examined in HCC. R51211, known as itraconazole, has been safely employed in clinical practice. Through in vitro and in vivo investigations, we assessed the potential of R51211 to enhance the therapeutic efficacy of sorafenib by inhibiting the hedgehog signaling. The zero-interaction potency synergy model demonstrated a synergistic interaction between R51211 and sorafenib, a phenomenon reversed by the action of a smoothened receptor agonist. This dual therapy exhibited an increased capacity to induce apoptosis, as evidenced by alterations in the Bax/BCL-2 ratio and caspase-3, along with a propensity to promote autophagy, as indicated by changes in BECN1, p62, and the LC3I/LC3II ratio. Furthermore, the combination therapy resulted in significant reductions in biomarkers associated with liver preneoplastic alterations, improved liver microstructure, and mitigated changes in liver function enzymes. The substantial decrease in hedgehog components (Shh, SMO, GLI1, and GLI2) following R51211 treatment appears to be a key factor contributing to the increased efficacy of sorafenib. In conclusion, our study highlights the potential of R51211 as an adjunct to sorafenib, introducing a new dimension to this combination therapy through the modulation of the hedgehog signaling pathway. Further investigations are essential to validate the therapeutic efficacy of this combined approach in inhibiting the development of liver cancer.

A novel combination therapy targets sonic hedgehog signaling by the dual inhibition of HMG-CoA reductase and HSP90 in rats with non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is characterized by liver inflammation, fat accumulation, and collagen deposition. Due to the limited availability of effective treatments, there is a pressing need to develop innovative strategies. Given the complex nature of the disease, employing combination approaches is essential. Hedgehog signaling has been recognized as potentially promoting NASH, and cholesterol can influence this signaling by modifying the conformation of PTCH1 and SMO activity. HSP90 plays a role in the stability of SMO and GLI proteins. We revealed significant positive correlations between Hedgehog signaling proteins (Shh, SMO, GLI1, and GLI2) and both cholesterol and HSP90 levels. Herein, we investigated the novel combination of the cholesterol-lowering agent lovastatin and the HSP90 inhibitor PU-H71 in vitro and in vivo. The combination demonstrated a synergy score of 15.09 and an MSA score of 22.85, as estimated by the ZIP synergy model based on growth inhibition rates in HepG2 cells. In a NASH rat model induced by thioacetamide and a high-fat diet, this combination therapy extended survival, improved liver function and histology, and enhanced antioxidant defense. Additionally, the combination exhibited anti-inflammatory and anti-fibrotic potential by influencing the levels of TNF-α, TGF-ß, TIMP-1, and PDGF-BB. This effect was evident in the suppression of the Col1a1 gene expression and the levels of hydroxyproline and α-SMA. These favorable outcomes may be attributed to the combination's potential to inhibit key Hedgehog signaling molecules. In conclusion, exploring the applicability of this combination contributes to a more comprehensive understanding and improved management of NASH and other fibrotic disorders.

The role of matrix metalloproteinase-2 and miR-196a2 in bronchial asthma pathogenesis and diagnosis.

Background: Bronchial asthma is a persistent inflammatory respiratory condition that restricts the passage of air and causes hyperresponsiveness. Chronic asthma can be classified into three categories: mild, moderate, and severe. Remodeling took place as the extracellular matrix accumulated in the walls of the airways. Inflammation occurs as a result of the damage caused by matrix metalloproteinase-2 (MMP-2) to basement membrane type IV collagen. The severity of asthma may be associated with miR-196a2. The objective of our study was to investigate the underlying mechanisms and clinical relevance of miR-196a2 and MMP-2 serum levels in relation to the severity of asthma. Methods: This study recruited 85 controls and 95 asthmatics classified as mild, moderate, or severe. Expression of miR-196a2 was measured by quantitative reverse transcriptase PCR. Using the enzyme-linked immunosorbent assay (ELISA), MMP-2, IL-6, and total immunoglobulin E (IgE) levels in the serum of asthmatics of various grades were compared to a control group. MMP-2's diagnostic and prognostic potential was determined using ROC curve analysis. This study also measured blood Eosinophils and PFTs. We examined MMP-2's connections with IgE, blood Eosinophils, and PFTs. Results: The current investigation found that miR-196a2 expression was significantly higher in the control group than in asthmatic patients as a whole. The study found that severe asthmatics had higher MMP-2, IL-6, and IgE serum levels than healthy controls. We identified the MMP-2 serum concentration cutoff with great sensitivity and specificity. Significant relationships between MMP-2 serum level and miR-196a2 expression in the patient group with severe asthmatics were found. The MMP-2, IL-6, and IgE serum levels were considerably higher in mild, moderate, and severe asthmatics than controls. The miR-196a2 expression and MMP-2 serum concentration correlated positively with IgE and blood eosinophils % and negatively with all lung function tests in the asthmatic patient group.Conclusion: the study revealed that the elevated miR-196a2 expression and serum concentration of MMP-2, IL-6, and IgE associated with elevated blood eosinophils % is associated with pathophysiology and degree of asthma severity. The miR-196a2 expression and MMP-2 serum concentration have a promising diagnostic and prognostic ability in bronchial asthma.

Linagliptin, a DPP-4 inhibitor, activates AMPK/FOXO3a and suppresses NFκB to mitigate the debilitating effects of diethylnitrosamine exposure in rat liver: Novel mechanistic insights.

Accumulating evidence suggests that dysregulation of FOXO3a plays a significant role in the progression of various malignancies, including hepatocellular carcinoma (HCC). FOXO3a inactivation, driven by oncogenic stimuli, can lead to abnormal cell growth, suppression of apoptosis, and resistance to anticancer drugs. Therefore, FOXO3a emerges as a potential molecular target for the development of innovative treatments in the era of oncology. Linagliptin (LNGTN), a DPP-4 inhibitor known for its safe profile, has exhibited noteworthy anti-inflammatory and anti-oxidative properties in previous in vivo studies. Several potential molecular mechanisms have been proposed to explain these effects. However, the capacity of LNGTN to activate FOXO3a through AMPK activation has not been investigated. In our investigation, we examined the potential repurposing of LNGTN as a hepatoprotective agent against diethylnitrosamine (DENA) intoxication. Additionally, we assessed LNGTN's impact on apoptosis and autophagy. Following a 10-week administration of DENA, the liver underwent damage marked by inflammation and early neoplastic alterations. Our study presents the first experimental evidence demonstrating that LNGTN can reinstate the aberrantly regulated FOXO3a activity by elevating the nuclear fraction of FOXO3a in comparison to the cytosolic fraction, subsequent to AMPK activation. Moreover, noteworthy inactivation of NFκB induced by LNGTN was observed. These effects culminated in the initiation of apoptosis, the activation of autophagy, and the manifestation of anti-inflammatory, antiproliferative, and antiangiogenic outcomes. These effects were concomitant with improved liver function and microstructure. In conclusion, our findings open new avenues for the development of novel therapeutic strategies targeting the AMPK/FOXO3a signaling pathway in the management of chronic liver damage.

Itraconazole halts hepatocellular carcinoma progression by modulating sonic hedgehog signaling in rats: A novel therapeutic approach.

Liver cancer stands as the fourth leading global cause of death, and its prognosis remains grim due to the limited effectiveness of current medical interventions. Among the various pathways implicated in the development of hepatocellular carcinoma (HCC), the hedgehog signaling pathway has emerged as a crucial player. Itraconazole, a relatively safe and cost-effective antifungal medication, has gained attention for its potential as an anticancer agent. Its primary mode of action involves inhibiting the hedgehog pathway, yet its impact on HCC has not been elucidated. The main objective of this study was to investigate the effect of itraconazole on diethylnitrosamine-induced early-stage HCC in rats. Our findings revealed that itraconazole exhibited a multifaceted arsenal against HCC by downregulating the expression of key components of the hedgehog pathway, shh, smoothened (SMO), and GLI family zinc finger 1 (GLI1), and GLI2. Additionally, itraconazole extended survival and improved liver tissue structure, attributed mainly to its inhibitory effects on hedgehog signaling. Besides, itraconazole demonstrated a regulatory effect on Notch1, and Wnt/ß-catenin signaling molecules. Consequently, itraconazole displayed diverse anticancer properties, including anti-inflammatory, antiangiogenic, antiproliferative, and apoptotic effects, as well as the potential to induce autophagy. Moreover, itraconazole exhibited a promise to impede the transformation of epithelial cells into a more mesenchymal-like phenotype. Overall, this study emphasizes the significance of targeting the hedgehog pathway with itraconazole as a promising avenue for further exploration in clinical studies related to HCC treatment.

Influence of high porous sponges for improving the interfacial evaporation from hemispherical solar distillers.

The present study aims to improve the palatable water production from the hemispherical cover solar distiller (HSD). To augment the palatable water produced from the hemispherical cover, a black sponge was utilized as a porous medium using different thicknesses, which augments the interfacial evaporation through the capillary effect of the water through the sponge. The rate of condensation of the hemispherical cover depends on the higher interaction of air from the ambient through wind velocity as the exposure area of the hemispherical cover is relatively higher as compared to the other traditional distillers. The rate of evaporation from the distillers depends on the interfacial materials used in the distillation unit, and this is achieved by using a highly porous black sponge to attain a higher evaporation rate. The thickness of the black porous sponge was optimized (1 to 4 cm), which was the operating parameter for better interfacial evaporation through the sponge, and the same has been compared to the conventional HSD without a porous sponge medium. Results showed a significant improvement in the evaporation rate using a porous medium as the palatable water produced from the HSD was improved by 72.29% using 3 cm as sponge thickness inside compared to the conventional HSD without the porous medium. The cumulative palatable water produced from the HSD using 3 cm as sponge thickness was found as 7150 mL/m2, whereas the conventional HSD without sponge, it was found as 4150 mL/m2. Moreover, using a porous sponge layer as an interfacial evaporation medium, the exergy and energy efficiencies were improved by about 512.87 and 70.53%, respectively. Similarly, with the influence of a porous sponge as an interfacial evaporation medium, the distilled water cost decreased by 41.67% more than the conventional HSD.

Interleukin-37 has A Promising Cardioprotective Effect on Isoproterenol-Induced Myocardial Infarction / La Interleucina-37 tiene un Efecto Cardioprotector Prometedor sobre el Infarto de Miocardio Inducido por Isoproterenol

SUMMARY: The main cause of mortality and disability globally is myocardial infarction (MI). Isoproterenol (ISO), a β-adrenoceptor agonist, has been used to induce rat myocardial necrosis. Whereas interleukin-37 (IL-37) has anti-inflammatory and cytoprotective properties. The study aimed to investigate the potential protective effects of IL-37 administration on cardiac architecture, oxidative stress, and inflammatory markers during ISO-induced MI in rats. Three groups of adult male rats were used in this study, the normal control group (n=8), ISO-induced MI group (n=8) that received isoproterenol hydrochloride (ISO) (100 mg/kg/day, SC, for the first 2 consecutive days), and IL-37-treated group (ISO+IL-37) (n=8) that received recombinant human IL-37 (40 µg/kg /day, intraperitoneally, for 2 weeks during and after ISO injections. Heart rate (HR.) and ECG changes were monitored. Some oxidative stress markers such as superoxide dismutase (SOD), nitric oxide (NOx), malondialdehyde (MDA), and glutathione (GSH) tissue levels in the tissue homogenate were assayed. Interleukin- 6 (IL-6), tumor necrosis factor- α (TNF-α), caspase-8, P53, and C- reactive protein (CRP) were among the inflammatory markers examined. In addition, serum levels of creatinine kinase (CK-MB) and lactate dehydrogenase (LDH) were analyzed to evaluate the myocardial injury. For histological analysis, tissues were sectioned, fixed in paraffin, and stained with hematoxylin and eosin (H&E), Masson Trichrome and, immunohistochemical against NF-kB, TNF-α, and Caspase-9. IL-37 improved ECG changes, cardiac enzyme markers, and some inflammatory markers of oxidative stress in ISO-induced MI. It also improved the histopathological and immunohistochemical changes in MI. In conclusion: IL-37 might be a promising therapeutic modality in myocardial infarction.

La principal causa de mortalidad y discapacidad a nivel mundial es el infarto de miocardio (IM). El isoproterenol (ISO), un agonista de los receptores adrenérgicos β, se ha utilizado para inducir necrosis miocárdica en ratas. Mientras que la interleucina-37 (IL-37) tiene propiedades antiinflamatorias y citoprotectoras. El estudio tuvo como objetivo investigar los posibles efectos protectores de la administración de IL-37 en la arquitectura cardíaca, el estrés oxidativo y los marcadores inflamatorios durante el infarto de miocardio inducido por ISO en ratas. En este estudio se utilizaron tres grupos de ratas macho adultas, el grupo control normal (n=8), el grupo con IM inducido por ISO (n=8) que recibió clorhidrato de isoproterenol (ISO) (100 mg/kg/día, SC, durante los primeros 2 días consecutivos) y el grupo tratado con IL-37 (ISO+IL- 37) (n=8) que recibió IL-37 humana recombinante (40 µg/kg/día, por vía intraperitoneal, durante 2 semanas durante y después de las inyecciones de ISO. Se monitorearon la frecuencia cardíaca (FC) y los cambios en el ECG. Se analizaron algunos marcadores de estrés oxidativo como la superóxido dismutasa (SOD), el óxido nítrico (NOx), el malondialdehído (MDA) y los niveles tisulares de glutatión (GSH) en el homogeneizado de tejido. La interleucina-6 (IL-6), el factor de necrosis tumoral-α (TNF-α), la caspasa-8, la P53 y la proteína C reactiva (CRP) se encontraban entre los marcadores inflamatorios examinados. Se analizaron los niveles de creatinoquinasa (CK-MB) y lactato deshidrogenasa (LDH) para evaluar la lesión miocárdica; para el análisis histológico se seccionaron los tejidos, se fijaron en parafina y se tiñeron con hematoxilina y eosina (H&E), Tricromo de Masson e inmunohistoquímica contra NF-kB, TNF-α y Caspasa-9. IL-37 mejoró los cambios de ECG, los marcadores de enzimas cardíacas y algunos marcadores inflamatorios de estrés oxidativo en el IM inducido por ISO. Además mejoró los cambios histopatológicos e inmunohistoquímicos en MI. En conclusión: la IL-37 podría ser una modalidad terapéutica prometedora en el infarto de miocardio.

Utility of the 4C ISARIC mortality score in hospitalized COVID-19 patients at a large tertiary Saudi Arabian center.

Background: The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) 4C mortality score has been used before as a valuable tool for predicting mortality in COVID-19 patients. We aimed to address the utility of the 4C score in a well-defined Saudi population with COVID-19 admitted to a large tertiary referral hospital in Saudi Arabia. Methods: A retrospective study was conducted that included all adults COVID­19 patients admitted to the Armed Forces Hospital Southern Region (AFHSR), between January 2021 and September 2022. The receiver operating characteristic (ROC) curve depicted the diagnostic performance of the 4C Score for mortality prediction. Results: A total of 1,853 patients were enrolled. The ROC curve of the 4C score had an area under the curve of 0.73 (95% CI: 0.702-0.758), p<0.001. The sensitivity and specificity with scores >8 were 80% and 58%, respectively, the positive and negative predictive values were 28% and 93%, respectively. Three hundred and sixteen (17.1%), 638 (34.4%), 814 (43.9%), and 85 (4.6%) patients had low, intermediate, high, and very high values, respectively. There were significant differences between survivors and non-survivors with regard to all variables used in the calculation of the 4C score. Multivariable logistic regression analysis revealed that all components of the 4C score, except gender and O2 saturation, were independent significant predictors of mortality. Conclusions: Our data support previous international and Saudi studies that the 4C mortality score is a reliable tool with good sensitivity and specificity in the mortality prediction of COVID-19 patients. All components of the 4C score, except gender and O2 saturation, were independent significant predictors of mortality. Within the 4C score, odds ratios increased proportionately with an increase in the score value. Future multi-center prospective studies are warranted.

Memantine mitigates ROS/TXNIP/NLRP3 signaling and protects against mouse diabetic retinopathy: Histopathologic, ultrastructural and bioinformatic studies.

Diabetic retinopathy (DRET) triggers vision loss in adults, however, little therapeutic options are existing. Memantine is an anti-Alzheimer drug that antagonizes the activity of glutamate at N-methyl-D-aspartate (NMDA) receptors. Glutamate and thioredoxin-interacting protein (TXNIP) are known to be overexpressed in diabetic retinas and can produce activation of NOD-like receptor protein 3 (NLRP3) with subsequent secretion of interlukin-1ß. This study repurposed memantine for its neuroprotective effect in experimental DRET and tested its impact on ROS/TXNIP/NLRP3. In addition, KEGG pathway database and STRING database identified the protein-protein interaction between glutamate receptors and TXNIP/NLRP3. Male Swiss albino mice received alloxan (180 mg/kg) to induce DRET. After 9 weeks, we divided the mice into groups: (a) saline, (ii) DRET, (iii and iv) DRET + oral memantine (5 or 10 mg per kg) for 28 days. Then, mice were euthanized, and eyeballs were removed. Retinal samples were utilized for biochemical, histopathological, and electron microscopy studies. Retinal levels of glutamate, TXNIP, NLRP3 and interlukin-1ß were estimated using ELISA technique as well as retinal malondialdehyde. Histopathological and ultrastructural examination demonstrated that oral memantine attenuated vacuolization and restored normal retinal cell layers. Moreover, memantine reduced TXNIP, NLRP3, interleukin-1ß and MDA concentrations. These results provide evidence demonstrating memantine' efficacy in alleviating DRET via suppressing reactive oxygen species/TXNIP/NLRP3 signaling cascade. Therefore, memantine might serve as a potential therapy for retinopathy after adequate clinical research.

Topiramate affords neuroprotection in diabetic neuropathy model via downregulating spinal GFAP/inflammatory burden and improving neurofilament production.

The current study aimed to test the neuroprotective action of topiramate in mouse peripheral diabetic neuropathy (DN) and explored some mechanisms underlying this action. Mice were assigned as vehicle group, DN group, DN + topiramate 10-mg/kg and DN + topiramate 30-mg/kg. Mice were tested for allodynia and hyperalgesia and then spinal cord and sciatic nerves specimens were examined microscopically and neurofilament heavy chain (NEFH) immunostaining was performed. Results indicated that DN mice had lower the hotplate latency time (0.46-fold of latency to licking) and lower von-Frey test pain threshold (0.6-fold of filament size) while treatment with topiramate increased these values significantly. Sciatic nerves from DN control mice showed axonal degeneration while spinal cords showed elevated GFAP (5.6-fold) and inflammatory cytokines (∼3- to 4-fold) but lower plasticity as indicated by GAP-43 (0.25-fold). Topiramate produced neuroprotection and suppressed spinal cord GFAP/inflammation but enhanced GAP-43. This study reinforces topiramate as neuroprotection and explained some mechanisms included in alleviating neuropathy.

Energy, exergy, and economic analysis of solar still using coal cylinder fins: an experimental study.

The phenomenon of drinking water scarcity has turned into the foremost issue that the world's populace is facing today. The Algerian desert regions, including the El Oued region (southeastern Algeria), also suffer from drinking water shortages, despite the presence of huge quantities of underground salty water. Solar distillation is among the easy and cheap solutions to solve this problem because this method relies on renewable energy (solar energy) as a key factor in providing drinking water from saltwater. As solar energy is intermittent energy, energy storage is required for augmenting the yield. Coal cylinders are low cost and locally available materials that can be used as fins and energy storage materials. In this research, two solar stills such as conventional solar still with a black absorber (CSS-BA) and CSS with a black absorber and coal cylinders (CSS-BA&CC) were fabricated and tested. The CSS-BA&CC produced a potable water yield of about 4.16 kg per day while the CSS-BA could only produce 2.88 kg, which is 44.44% lower when compared to the CSS-BA&CC. The thermal efficiency was noted to be 22.04 % and the exergy efficiency is 1.07 % in the CSS-BA. Similarly, the thermal efficiency is 32.46% and exergy efficiency is 1.90% for the CSS-BA&CC. The experimental results proved that the potable water yield of the CSS-BA was enhanced by coal cylinders (sensible heat energy storage material -SHESM) which is a locally available low-cost material.

Hemispherical solar distiller with truncated circular cone-shaped reflector mirrors (TCC-RM): optimum inclination of reflector mirrors.

The present study aims to achieve the highest cumulative yield of the hemispherical distillers, by designing and constructing new reflector mirrors, which are truncated circular cone-shaped reflector mirrors (TCC-RM). To obtain the optimum inclination of TCC-RM that achieves the highest hemispherical distiller's performance, eight inclination angles (10°, 15°, 20°, 25°, 30°, 35°, 40°, and 45° with vertical) were experimentally studied. To achieve this, a series of experimental tests were carried out on the three hemispherical solar distillers: the first represents the reference distiller (traditional hemispherical solar distiller (THSD)) and the other two devices are the hemispherical solar distiller with truncated circular cone-shaped reflector mirrors (HSD-TCCRM) with different inclination angles. The experimental results indicate that utilizing TCC-RM with a 25° inclination angle achieves the maximum cumulative yield of 8.35 L/m2 with an improvement of 42.74% compared to THSD. While the utilization of TCC-RM with the inclination angles of 30°, 35°, 20°, 40°, and 15° achieves the cumulative yield of 7.9, 7.3, 7.05, 6.67, and 6.6 L/m2 compared with 5.85 L/m2 for THSD. On the contrary, adjusting the inclination angle of TCC-RM at 10° and 45° affects negatively the cumulative yield of the HSD with TCC-RM in comparison with THSD. Based on the data of cumulative yield, daily efficiency, and the economic analysis it is recommended to utilize TCC-RM with a 25° inclination angle to achieve the highest performance and minimum distillate cost of hemispherical solar distillers.

Hemispherical Solar Distiller Performance Utilizing Hybrid Storage Media, Paraffin Wax with Nanoparticles: An Experimental Study.

The traditional method of obtaining fresh water for drinking is by burning fossil fuels, emitting greenhouse gases into the atmosphere. However, renewable energy is gaining more traction since it is available free of cost for producing fresh water. In this study, Al2O3 nanoparticles were distributed in a phase change material (paraffin wax) that had been fixed at a hemispherical distiller water basin. Three scenarios with three hemispherical distillers were examined. A conventional hemispherical distiller (CHD), a conventional hemispherical distiller with paraffin wax as a phase change material (CHD-PCM), and a conventional hemispherical distiller with PCM partially filled with Al2O3 nanoparticles (CHD-N-PCM) were tested under the same climatic conditions. The experimental results showed that CHD gave a daily yield of 4.85 L/m2/day, while CHD-PCM increased the yield to up to 6.2 L/m2/day with a 27.84% daily yield enhancement. The addition of Al2O3 nanoparticles to paraffin wax CHD-N-PCM improved hemispherical distillate yield up to 8.3 L/m2/day with a 71.13% increase over CHD yield.

Programmed death-ligand 1 (PD-L1) polymorphisms as predictive biomarkers for the development of liver cirrhosis and hepatocellular carcinoma in HCV Egyptian patients.

BACKGROUND: Considering the immune evasion role of programmed death-ligand 1 (PD-L1) in cancer development, its genomic variations might be closely associated with disease development and cancer risks. Accordingly, this study was performed to investigate how the PD-L1 gene polymorphisms affect the susceptibility to hepatitis C virus (HCV)-induced liver cirrhosis and cancer development in the Egyptian population. METHODOLOGY: Two single nucleotide polymorphisms of the PD-L1 gene; rs2297136 (A > G) and rs4143815 (C > G), were studied in 50 HCV, 51 liver cirrhosis, and 52 hepatocellular carcinoma (HCC) patients as well as 50 healthy subjects using real-time PCR. RESULTS: The frequencies of PD-L1 rs2297136 AA and rs4143815 GG genotypes were significantly higher in the liver cirrhosis than the control and HCV groups. The rs4143815 CG and GG genotypes were linked to a higher risk of developing HCC and were positively associated with the clinicopathological features of HCC. CONCLUSIONS: The PD-L1 rs2297136 AA and rs4143815 GG genotypes increase the susceptibility to liver cirrhosis. The rs4143815 CG and GG genotypes are positively associated with HCC risk and its clinicopathological characteristics. Therefore, HCV patients carrying the PD-L1 rs4143815 G-allele should be followed up on a regular basis to allow for early HCC management.

Ameliorated Stomach Specific Floating Microspheres for Emerging Health Pathologies Using Polymeric Konjac Glucomannan-Based Domperidone.

The goal of this study was to use polymeric konjac glucomannan (KGM), Kollidon VA 64 (KVA64), and glutaraldehyde to ameliorate stomach specific floating microspheres (SSFM) using domperidone (DoN) to increase in vivo bioavailability and emerging health pathologies. The SSFM were made using the emulsion cross-linking process, and the polymer was chosen based on its ability to get cross-linked. The thermodynamic parameters were used to determine the AL classes of phase solubility curves using ideal complexes produced with KVA64. The optimal interaction constants at 25 and 37°C were found to be 116.14 and 128.05 M-1, respectively. The prepared SSFM had an average particle size (PS) of 163.71 ± 2.26 mm and a drug content of 96.66 ± 0.32%. It can be determined from in vitro drug release experiments that drug release is good in terms of regulated drug release after 12 h (92.62 ± 2.43%). The SSFMs were approximately sphere-shaped and had smooth surfaces, according to the morphological data. SSFMs were investigated using Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), and differential scanning calorimetry (DSC), and no chemical structural changes were identified. The SSFMs produces a considerable gastric residence time with optimal DoN release and absorption in stomach fluid, and the mean residence time (17.36 ± 1.4 h) and t 1/2 (10.47 ± 0.6 h) were considerably longer (p < 0.05) than those obtained following i.v. treatment (MRT = 8.42 ± 1.2 h; t 1/2 = 9.07 ± 0.7 h). The SSFMs maintained good physical stability for three months when stored at room temperature.

Experimental investigation on a modified design of hemispherical solar distiller with v-corrugated iron trays and wick materials for improving freshwater production.

The low energy efficiency of the solar distillers is one of the key barriers to their effectual usage in the desalination domain. Hence, this work introduces an experimental investigation to enhance the freshwater productivity of the hemispherical solar distiller with different trays' configurations and utilizing wick materials. This was achieved by utilizing iron trays and wicks in the circular basin of hemispherical solar still in order to increase the vaporization surface area for better heat transfer of saline water. The performance of the hemispherical solar distiller was investigated with flat and v-corrugated iron trays configurations. Three distillers were designed and examined, namely, conventional hemispherical solar distiller, hemispherical solar distillery with flat iron trays, and hemispherical solar distiller with v-corrugated iron trays. Moreover, the combined effects of using wick materials with flat and v-corrugated iron trays in the basin of hemispherical distiller have been also investigated. Experiments were carried out at the desert climate conditions of El-Oued (33°27'N, 7°11'E), Algeria. The results showed that the productivity improvement is 42.85% and 14.30% over the conventional hemispherical distiller for v-corrugated and flat trays hemispherical solar still (HSD), respectively. While the inclusion of wick materials with v-corrugated iron trays further increases the productivity by about 83.12% over the reference distiller. Moreover, the energy efficiency of the flat trays HSD, v-corrugated trays HSD, HSD flat trays and wicks, and HSD v-corrugated trays and wicks is 38.72%, 48.28%, 52.16%, and 61.67%, respectively. Additionally, the .cost of freshwater production of HSD v-corrugated trays and wicks was 41.72% lower than that of a traditional hemispherical distiller.

Performance improvements of hemispherical solar still using internal aluminum foil sheet as reflector: energy and exergy analysis.

Various scientists are looking for effective and easy solutions for the augmentation of yield from the hemispherical solar still (HSS). In this study, aluminum foil sheet was used to reflect the intensity, hence augmenting the evaporation rate and daily yield. Experimentations were conducted on two SS: the first SS is HSS; the second SS is HSS with reflective aluminum foil sheet walls (HSS-RAFW). The highest distilled water production from the HSS and HSS-RAFW is 3.36 and 4.1 kg/m2, respectively. Compared to the HSS, the yield of distilled water was augmented by 22.21% when using the HSS-RAFW. The daily energy and exergy efficiencies (EnE and ExE) of the HSS are 26.27 and 1.04%, respectively, and the daily EnE and ExE of the HSS-RAFW are 32.75 and 1.71%, respectively.

Optimization of the hemispherical solar distiller performance assisted by high thermal conductivity metal trays incorporated with reflective mirrors.

The present comprehensive study aims to achieve the highest freshwater productivity of hemispherical solar distillers which are characterized by having a large condensing and receiving surface area. This was done by incorporating two effective modifications to the design of the hemispherical solar distiller, namely the use of metal trays with high thermal conductivity and reflective mirrors. In the present experimental work, three different high thermal conductivity metal trays (steel, zinc, and copper) incorporated with the reflective mirrors were tested under the same climate conditions, in order to determine the optimum selection of metal trays that are incorporated with the reflective mirrors that achieve the highest performance of the hemispherical distillers. To realize this objective, four distillers were fabricated and tested at the same climate condition namely: Hemispherical solar Distiller with Black Silicone Walls (HSD-BSW) which represent the reference case, Hemispherical Solar Distiller with Steel Trays and Reflective Mirrors (HSD-ST&RM), Hemispherical Solar Distiller with Zinc Trays and Reflective Mirrors (HSD-ZT&RM), and Hemispherical Solar Distiller with Copper Trays and Reflective Mirrors (HSD-CT&RM). The experimental results presented that the utilization of copper trays incorporated with reflective mirrors (HSD-CT&RM) represents the very effective option to achieve the highest performance of the hemispherical solar distillers. The cumulative production achieve by the reference HSD-BSW reached 4.65 l/m2day, while utilization of copper trays incorporated with reflective mirrors (HSD-CT&RM) increases the cumulative production to 9.5 l/m2day, with an improvement of 104.3%. Also, utilization of copper trays incorporated with reflective mirrors (HSD-CT&RM) improves the daily thermal and exergy efficiencies by 102.4% and 194.9%, respectively compared to HSD-BSW. Additionally, the economic feasibility showed that the use of copper trays incorporated with reflective mirrors (HSD-CT&RM) is a very effective option as it reduces the cost of distilled water by 44.1%.

Enhancing the hemispherical solar distiller performance using internal reflectors and El Oued sand grains as energy storage mediums.

This paper presents a comprehensive experimental study of the some effective modifications which aim to improve the cumulative productivity of solar distillers, in order to reach the best modification that achieves the highest cumulative productivity of hemispherical distillates. The experimentations were carried on the hemispherical distillers which are characterized by a large area of receiving and condensation. To obtain the best modification that achieves the highest cumulative productivity, the present comprehensive studies were conducted on two experimental scenarios. In the first scenario, the influences of internal reflective (Reflective Mirrors and Reflective Aluminum Foil) on hemispherical distillers performance was studied. In the second scenario, the influences of internal reflective with El-Oued sand grains as the energy store mediums on hemispherical distiller performances was studied. To achieve this goal, we designed and fabricated three hemispherical distillers, the first distiller represents the reference case (Conventional Hemispherical Solar Still-CHSS), the second is the Hemispherical Solar Still with Internal Reflective Mirrors (HSS-IRM), and a third is the Hemispherical Solar Still with Internal Reflective Aluminum Foil (HSS-IRAF). In the second experimental scenario, the El-Oued sand grains were added to the basin of the second and third distillers as follows; where the second distiller became a Hemispherical Solar Still with Internal Reflective Mirrors and El-Oued sand grains (HSS-IRM & SG), and a third distiller became a Hemispherical Solar Still with Internal Reflective Aluminum Foil and El-Oued sand grains (HSS-IRAF & SG). The results presented that the cumulative production of reference distiller (CHSS) up to 4750 mL/m2, while use of internal reflective mirrors and El-Oued sand grains (HSS-IRM & SG) increases the production to 9400 mL/m2 day. The maximum improvement in cumulative distillate production, exergy efficiency, and thermal efficiency was recorded for utilization of internal reflective mirrors and El-Oued sand grains (HSS-IRM & SG) which reached 98, 200.9, and 96%, respectively, compared to reference case (CHSS). The economic feasibility indicated that the utilization of HSS-IRM & SG represent the good modification which reduced the cost of freshwater productivity by 49.1% compared to CHSS.

Impact of water depth on thermal efficiency, exergy efficiency, and exergy losses of finned acrylic solar still: an experimental study.

This paper presents a complete exergy analysis and exergy destruction of a finned acrylic solar still (SS) at 1, 2, and 3 cm salt water depth (Wd). The coefficients of heat transfer of salt water-glass have been computed for evaporative, convective, and radiant heat transfer. Also, thermal efficiency, exergy loss of basin, saltwater, and glass was determined. The maximum hourly output of a finned acrylic SS at 1, 2, and 3 cm Wd was1.23, 0.93, and 0.81 kg, respectively. The daily yield of 5.67, 5.16, and 4.41 kg was collected from the finned acrylic SS at 1, 2, and 3 cm salt Wd, respectively. For the finned acrylic SS at 1 cm Wd, the maximal exergy loss of the basin, saltwater, and glass was 604.3, 92.8, and 141.8 W/m2, respectively. The thermal and exergy efficiency of the finned acrylic SS at 1 cm Wd is 42.54 and 3.83%, respectively, while at 2 cm salt Wd, it is 37.92 and 3.22% and for 3 cm Wd is 31.2 and 2.7%. According to the findings, the exergy loss of saltwater in finned acrylic SS at 1 cm Wd is minimal when compared to the exergy loss of saltwater in finned acrylic SS at 2 and 3 cm Wd.