Walrus optimizer-based optimal fractional order PID control for performance enhancement of offshore wind farms.

Offshore wind farms (OWFs) play a crucial role in producing renewable energy in modern electrical power systems. However, to ensure that these facilities operate smoothly, they require robust control systems. As a result, this paper employed the newly developed Walrus Optimization algorithm (WaOA) to optimize the design parameters of fractional-order proportional-integral-derivative (FOPID) controllers in the power electronic interface circuits of the studied wind energy conversion system (WECS). In contrast to conventional optimization techniques like GA and PSO, the suggested approach proves more effective. The paper validates the WaOA application in optimizing FOPID controllers within a WECS comprising two, onshore and offshore, VSC stations at the two ends of an HVDC transmission system connecting OWFs to the mainland. The study shows that the WaOA outperforms GA and PSO, improving system stability and enabling quick recovery after disturbances. The study carried out using MATLAB/Simulink highlights the significance of newly recently introduced optimization techniques to ensure efficient and reliable operation of offshore wind energy systems, thereby expediting the transition to sustainable energy sources.

SARS-CoV-2 infection prevalence, risk factors, and outcomes among non-clinical-related service providers in a national healthcare system.

Health care workers (HCWs) may be at a variable risk of SARS-CoV2 infection. Regardless of their involvement in providing direct clinical treatment, most of the prior research had included all HCWs. Understanding infection rates, risk factors and outcomes among different subgroups of HCWs is crucial. From February 28, 2020 to January 1, 2022, we conducted a retrospective analysis encompassing all full-time non-clinical staff (NCS) subcontracted with Hamad Medical Corporation (HMC) facilities. To determine current or previous SARS-CoV2 infection, all personnel underwent RT-PCR and/or serology testing. To identify the demographic factors linked to the risk of infection, we utilized Cox-Hazard regression analysis. Herein 3158/6231 (50.7%) subcontracted NCS tested positive for SARS-CoV-2 by RT-PCR or serology during the research period. The median age was 30 years (IQR 25,35), 69.8% of the population were males, 82.4% were from South Asia, 86.6% did not have any concomitant conditions. 6032 (96.8%) of the population lived in shared housing, while 4749 (76.2%) had low to median levels of education. While infection (PCR positive with or without seropositive results) was independently predicted by male gender, working in the catering, laundry, and security sectors and being intermediate (7-12 years of education), lower (0-6 years of education), higher (exposure to confirmed case), and having symptoms. Male gender, working in the security sectors and being intermediate (7-12 years of education) were independently associated with accidently detected cases (PCR negative and seropositive). 299 (4.8%) required hospitalization, of them 3 cases were severe pneumonia and one required ICU admission without mechanical ventilation, with no deaths reported. In conclusion Infection rates among NCS are high. The majority are asymptomatic and may contribute to ongoing illness spread in the public or in healthcare facilities. During a pandemic, routine screening of this population is crucial and may aid in containing the spread of infection.

Evaluation of pollution levels in sediments from Lake Edku, Egypt using laser ablation inductively coupled plasma mass spectrometry.

The concentrations of 11 heavy metals in sediments from Lake Edku, Egypt were determined using LA-ICP-MS. The average concentrations of elements occurred in the order of Fe > V > Cr > Zn > Ni > Cu > Co > Pb > As > Sn > Mo with respective values of 4.67 %, 104.8, 77.9, 76.6, 59.2, 52, 27.8, 19.8, 4.14, 2.24, and 1.45 µg/g. Several pollution indices were used to evaluate individual and cumulative contamination levels. All HMs were found to be in the deficiency to minimal enrichment range based on the enrichment factor. The contamination factor indicated low contamination levels of Cr and As, low to moderate contamination levels of Fe, Ni, Zn, Mo, Sn, and Pb, and moderate contamination levels of Co and Cu. The pollution load index and contamination degree indicated the sediments to be polluted and moderately polluted, respectively.

Sacubitril/valsartan alleviates sunitinib-induced cardiac fibrosis and oxidative stress via improving TXNIP/TRX system and downregulation of NF-ĸB/Wnt/ß-catenin/SOX9 signaling.

We aimed in this study to investigate the possible cardioprotective effects of sacubitril/valsartan against sunitinib-induced cardiac fibrosis (CF) and oxidative stress via targeting thioredoxin-interacting protein/thioredoxin (TXNIP/TRX) system and nuclear factor-kappa B (NF-κB)/Wingless-related MMTV integration site (Wnt)/ß-catenin/Sex-determining region Y box 9 (SOX9) signaling. CF was induced in male Wistar albino rats by cumulative dose of sunitinib (300 mg/kg, given over 4 weeks as: 25 mg/kg orally, three times a week), which were co-treated with sacubitril/valsartan (68 mg/kg/day, orally) for four weeks. Significant elevation in blood pressure, cardiac inflammatory and fibrotic markers besides cardiac dysfunction were observed. These alterations were associated with disruption of TXNIP/TRX system, upregulation of NF-κB/Wnt/ß-catenin/SOX9 pathway along with marked increase in lysyl oxidase (LOX) and matrix metalloproteinase-1 (MMP-1) expressions and extensive deposition of collagen fibers in cardiac tissues. Luckily, sacubitril/valsartan was able to reverse all of the aforementioned detrimental effects in sunitinib-administered rats. These findings illustrate a potential role of sacubitril/valsartan in alleviating CF and oxidative stress induced by sunitinib via antioxidant, anti-inflammatory and antifibrotic properties. These remarkable effects of sacubitril/valsartan were mediated by its ability to improve TXNIP/TRX system and downregulate NF-κB/Wnt/ß-catenin/SOX9 signaling in addition to decreasing LOX and MMP-1 expressions in cardiac tissues. In summary, this study highlights sacubitril/valsartan as a potential therapeutic agent in mitigating CF and oxidative stress especially in cancer cases treated with sunitinib.

Detection and quantification of adenovirus, polyomavirus, and papillomavirus in urban sewage.

The objective of this study was to assess the occurrence and seasonal frequency of human adenovirus (HAdV), human polyomavirus (HPyV), and human papillomavirus (HPV) in urban sewage. The detection of these viruses was carried out by polymerase chain reaction (PCR), and then the viral concentrations in the positive samples were quantified by quantitative PCR (qPCR). Additionally, HAdV and HPyV genotyping was also performed by PCR. A total of 38/60 (63.3%) positive samples were found. HAdV was the most prevalent virus (26/60; 43.3%), followed by HPyV (21/60; 35%) and HPV (21/60; 35%). The viral concentrations ranged from 3.56 × 102 to 7.55 × 107 genome copies/L. The most common dual viral agents was found between HAdV and HPyV, in eight samples (8/38, 21%). HAdV types 40 and 41 as well as HPyV types JC and BK were identified, with HAdV-40 and HPyV JC being the most prevalent types. Furthermore, the detection rates of HAdV, HPyV, and HPV were higher during the winter season than the other seasons. The high prevalence of HAdV and HPyV supports their suitability as viral indicators of sewage contamination. Furthermore, this study demonstrates the advantages of environmental surveillance as a tool to elucidate the community-circulating viruses.

Effect of platelet rich plasma versus melatonin on testicular injury induced by Busulfan in adult albino rats: a histological and immunohistochemical study.

This study was done to estimate the testicular histological alterations induced by Busulfan (BUS) and compare the possible protective effects of melatonin (MT) and platelet rich plasma (PRP) in a rat model. Sixty-four male rats were dispersed into: control group, BUS group, melatonin group, and PRP group. Blood samples were processed for biochemical analysis. Tissue specimens were managed for light and electron microscopic studies. Immunohistochemical expression of vimentin and proliferating cell nuclear antigen (PCNA) was performed. Busulfan induced severe testicular damage in all studied methodologies. It showed a statistically significant decrease in serum testosterone and elevation of MDA when compared to the control group. Abnormal testicular cytostructures suggesting defective spermatogenesis were observed: distorted seminiferous tubules, deformed spermatogenic cells, low germinal epithelium height, few mature spermatozoa, and also deformed barrier. Vimentin and PCNA expressions were reduced. Ultrastructurally, Sertoli cells and the blood testis barrier were deformed, spermatogenic cells were affected, and mature spermatozoa were few and showed abnormal structure. Both melatonin and PRP induced improvement in all the previous parameters and restoration of spermatogenesis as confirmed by improvement of Johnsen's score from 2.6 ± .74 to 7.6 ± .92. In conclusion, melatonin and PRP have equal potential to ameliorate the testicular toxicity of BUS. Melatonin can provide a better noninvasive way to combat BUS induced testicular injury.

Unraveling IL-17 and IL-22 role in occult hepatitis C versus chronic hepatitis C virus infection.

BACKGROUND: Cytokines play a crucial role in regulating the function of the immune system by controlling the production, differentiation, and activity of immune cells. Occult hepatitis C virus (OHCV) infection can lead to liver damage, including cirrhosis and hepatocellular carcinoma. This study investigates the immunopathogenic impact of the cytokines IL-17 and IL-22 in OHCV infection compared to chronic hepatitis C (CHC) infection. METHODS: We studied three groups of patients: 35 with OHCV, 100 untreated patients with CHC, and 30 healthy control subjects. All subjects underwent physical examination and biochemical testing. We used the sandwich enzyme-linked immunosorbent assay method to measure serum IL-17 and IL-22 levels in all groups. RESULTS: Compared to the occult and control groups, the CHC group had significantly higher serum IL-17 levels (p < 0.001). The occult group also had higher serum IL-17 levels compared to the control group (p < 0.0001). There were no significant differences in IL-22 levels across the research groups. In the OHCV group, individuals with moderate inflammation (A2-A3) had significantly higher serum IL-17 levels than those with minimal inflammation (A0-A1), while in the CHC group, this difference was not statistically significant (p = 0.601). Neither the occult nor the CHC groups showed a correlation between serum IL-22 and inflammatory activity. There was no significant correlation between the levels of IL-17 or IL-22 and the stage of fibrosis/cirrhosis in either group. ROC curves were calculated for serum IL-17 and IL-22 levels and occult HCV infection, with cut-off values set at ≤ 32.1 pg/ml and < 14.3 pg/ml for IL-17 and IL-22, respectively. The AUROC (95%CI) was significantly higher for IL-17 than IL-22 (0.829 (0.732-0.902) vs. 0.504 (0.393-0.614), p < 0.001), suggesting that IL-17 has a stronger correlation with infection risk than IL-22. CONCLUSION: This study suggests that IL-17 may be involved in the immunopathogenesis of OHCV infection, especially in patients with moderate inflammation.

Silver and gold nanoparticles: Eco-friendly synthesis, antibiofilm, antiviral, and anticancer bioactivities.

For the first time in this study, silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) were green synthesized by the cost-effective and eco-friendly procedure using Cotton seed meal and Fodder yeast extracts. The biosynthesized NPs were characterized by UV-Vis spectroscopy, dynamic light scattering analysis (DLS), transmission electron microscopy (TEM), selected area electron diffraction (SAED), and fourier-transform infrared (FTIR) spectroscopy. Furthermore, the biosynthesized NPs were tested in vitro against biofilm formation by some pathogenic negative bacteria (Escherichia coli, Proteus mirabilis, Klebsiella sp., Salmonella sp., and Pseudomonas aeruginosa) and negative bacteria (staphylococcus aureus) as well as against human denovirus serotype 5 (HAdV-5) and anticancer activity using HepG2 hepatocarcinoma cells. UV-Vis absorption spectra of reaction mixture of AgNPs and AuNPs exhibited maximum absorbance at 440 nm and 540 nm, respectively. This finding was confirmed by DLS measurements that the highest intensity of the AgNPs and AuNPs were 84 nm and 73.9 nm, respectively. FTIR measurements identified some functional groups detected in Cotton seed meal and Fodder yeast extracts that could be responsible for reduction of silver and gold ions to metallic silver and gold. The morphologies and particle size of AgNPs and AuNPs were confirmed by the TEM and SAED pattern analysis. Biosynthesized AgNPs and AuNPs showed good inhibitory effects against biofilms produced by Escherichia coli, Proteus mirabilis, Klebsiella sp., Salmonella sp., Pseudomonas aeruginosa, and Staphylococcus aureus. In addition, they showed anticancer activities against hepatocellular carcinoma (HepG-2) and antiviral activity against human adenovirus serotype 5 infection in vitro. Finally, the results of this study is expected to be extremely helpful to nano-biotechnology, pharmaceutical, and food packing applications through developing antimicrobial and/or an anticancer drugs from ecofriendly and inexpensive nanoparticles with multi-potentiality.

Enhancement of cardiac angiogenesis in a myocardial infarction rat model using selenium alone and in combination with PTXF: the role of Akt/HIF-1α signaling pathway.

Ischemic heart diseases such as myocardial infarction (MI) are a global health problem and a leading cause of mortality worldwide. Angiogenesis is an important approach for myocardial healing following ischemia. Thus, this study aimed to explore the potential cardiac angiogenic effects of selenium (Se), alone and in combination with the tumor necrosis factor-alpha inhibitor, pentoxifylline (PTXF), via Akt/HIF-1α signaling. MI was induced in rats using two subcutaneous doses of isoprenaline (ISP) at a 24-h interval (150 mg/kg). One week later, rats were orally given Se (150 µg/kg/day), PTXF (50 mg/kg/day), or Se/PTXF combination. ISP-induced myocardial damage was evident by increased HW/TL ratios, ST segment elevation, and increased serum levels of CK-MB, LDH, and troponin-I. ISP increased the cardiac levels of the lipid peroxidation marker MDA; the pro-inflammatory cytokines IL-6, IL-1ß, and TNF-α; and the pro-apoptotic protein Bax and caspase-3. In contrast, the cardiac levels of the antioxidant markers GSH and SOD and the anti-apoptotic marker Bcl-2 were reduced. Furthermore, ISP markedly increased the cardiac levels of p-Akt and HIF-1α proteins and the cardiac gene expression of ANGPT-1, VEGF, and FGF-2. Treatment with Se both alone and in combination with PTXF ameliorated the ISP-induced myocardial damage and further increased cardiac angiogenesis via Akt/HIF-1α signaling. Se/PTXF combined therapy was more beneficial than individual treatments. Our study revealed for the first time the cardiac angiogenic effects of Se both alone and in combination with PTXF in myocardial infarction, suggesting that both may be promising candidates for clinical studies.

Assessment of C-reactive protein levels as an indicator for lung infiltrates in patients with COVID-19 pneumonia.

Lung infiltrates are frequently observed in patients with COVID-19 infection and require specialized management. Identifying reliable laboratory parameters to reduce the need for chest CT scans in non-desaturation patients is of great interest. This study aimed to investigate the potential of C-reactive protein (CRP) as an indicator to identify the presence of lung infiltrates in early COVID-19 infection. The study was conducted at Al-Azhar University hospitals from May 2021 to March 2022 and included 210 patients with COVID-19 infection confirmed by positive PCR, all of whom were previously healthy, non-smokers, and non-hypoxemic. CRP levels were assessed and correlated with lung infiltrates observed in CT chest examinations. The mean value of CRP was 40.3±14.3 mg/L in males and 36.6±15.2 mg/L among females. One hundred sixty-two patients had pneumonic infiltrates, while 48 had no infiltrates. The mean value of CRP was 45.02±10.2 mg/L in patients with radiological infiltrates and 18.8±7.8 mg/L in patients without radiological infiltrates. Based on our findings, a CRP value greater than 29.8 mg/L was suggested as a cut-off value to indicate the presence of lung infiltrates. CRP is a simple laboratory marker that, at certain limits, may point to the presence of pneumonic infiltrates in early non-hypoxemic patients with COVID-19 infection.

Oral proniosomal amitriptyline and liraglutide for management of diabetic neuropathy: Exceptional control over hyperglycemia and neuropathic pain.

Exploitation of nanocarriers provides a compartment for enclosing drugs to protect them from degradation and potentiate their therapeutic efficiency. In the current study, amitriptyline- and liraglutide-loaded proniosomes were constructed for management of diabetic neuropathy, a serious complication associated with diabetes, that triggers spontaneous pain in patients and results in impaired quality of life. The developed therapeutic proniosomes were extensively characterized via dynamic light scattering, scanning electron microscopy, transmission electron microscopy, and Fourier transform-infrared spectroscopy. High entrapment efficiency could be attained for both drugs in the proniosomes, and the reconstituted amitriptyline- and liraglutide-loaded niosomes possessed spherical morphology and particle sizes of 585.3 nm and 864.4 nm, respectively. In a diabetic neuropathy rat model, oral administration of the developed amitriptyline- and liraglutide-loaded proniosomes significantly controlled blood glucose levels, reduced neuropathic pain, oxidative stress and inflammatory markers, and improved histological structure of the sciatic nerve as compared to the oral and subcutaneous administration of amitriptyline and liraglutide, respectively. Loading of the tricyclic antidepressant amitriptyline and the antidiabetic peptide liraglutide into proniosomes resulted in exceptional control over hyperglycemia and neuropathic pain, and thus could provide an auspicious delivery system for management of neuropathic pain and control of blood glucose levels.

Pentoxifylline as Add-On Treatment to Donepezil in Copper Sulphate-Induced Alzheimer's Disease-Like Neurodegeneration in Rats.

Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by behavioral, cognitive, and progressive memory impairments. Extensive neuronal loss, extracellular accumulation of insoluble senile amyloid-ß (Aß) plaques, and intracellular neurofibrillary tangles (NFTs) are the major pathological features. The present study aimed to investigate the therapeutic effect of donepezil (DON) and pentoxifylline (PTX) in combination to combat the neurodegenerative disorders (experimental AD) induced by CuSO4 intake in experimental rats. Thirty adult male Wistar rats (140-160 g) were used in this study. AD was first induced in rats by CuSO4 supplement to drinking water (10 mg/L) for 14 weeks. The AD group received no further treatment. Oral treatment with DON (10 mg/kg/day), PTX (100 mg/kg/day), or DON + PTX for the other three groups was started from the 10th week of CuSO4 intake for 4 weeks. Cortex markers like acetylcholine (ACh), acetylcholinesterase (AChE), total antioxidant capacity (TAC), and malondialdehyde (MDA) and hippocampus markers like ß-amyloid precursor protein cleaving enzyme 1 (BACE1), phosphorylated Tau (p-tau), Clusterin (CLU), tumor necrosis factor-α (TNF-α), caspase-9 (CAS-9), Bax, and Bcl-2 were measured. The histopathology studies were done by using hematoxylin and eosin and Congo red stains as well as immunohistochemistry for neurofilament. CuSO4 induced adverse histological and biochemical changes. The histological injury in the hippocampus was inhibited following the administration of the DON and PTX. The brain tissue levels of AChE, MDA, BACE1, p-tau, CLU, CAS-9, Bax, and TNF-α were significantly increased, while brain tissue levels of ACh, TAC, and Bcl-2 were significantly decreased in CuSO4-treated rats as compared with the untreated control group. The effects induced by either DON or PTX on most studied parameters were comparable. Combined treatment of DON and PTX induced remarkable results compared with their individual use. However, more clinical and preclinical studies are still required to further confirm and prove the long-term efficacy of such combination.

Raspberry ketone ameliorates nonalcoholic fatty liver disease in rats by activating the AMPK pathway.

The current study aimed to investigate the effect of orally administered raspberry ketone (RK) on ameliorating nonalcoholic fatty liver disease (NAFLD) induced in rats by high-fat high-fructose diet (HFFD) in comparison to calorie restriction (CR) regimen. Thirty male Wistar rats were divided into two experimental groups; one was fed normal chow diet (NCD, n = 6) for 15 weeks to serve as normal control group and the other group was fed HFFD (n = 24) for 7 weeks to induce NAFLD. After induction, rats in the HFFD group were randomly allocated into four groups (n = 6 rats each). One group continued on HFFD feeding for 8 weeks (NAFLD control group). The remaining 3 groups received NCD, calorie-restricted diet, or NCD along with RK (55 mg/kg/day, orally) for 8 weeks. Like CR, RK effectively attenuated NAFLD and ameliorated the changes attained by HFFD. RK upregulated the expression of the phosphorylated AMP-activated protein kinase (P-AMPK) and fatty acid oxidation factors; peroxisome proliferator-activated receptor alpha (PPAR-α) and carnitine palmitoyltransferase-1 (CPT-1) and downregulated lipogenic factors; sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) in the hepatic tissue. Also, RK improved lipid profile parameters, liver enzymes and both body and liver tissue weights. Altogether, these findings suggest that oral administration of RK, along with normal diet, ameliorated NAFLD in a way similar to CR. This approach could be an alternative to CR in the management of NAFLD, overcoming the poor compliance to long term CR regimen.

Comparative assessment of homemade ELISA and lateral flow assay (LFA)in the rapid, specific and sensitive detection of SARS-CoV-2 anti-nucleocapsid protein in sera of Egyptian patients.

Several diagnostic measures have been employed to precisely detect the SARS-CoV-2 viral infection using viral antigens, nucleic acids, and other serological approaches. The sensitivity and specificity of the serological tests remain a challenging need. Here, we describe the detection of human anti-SARS-CoV-2 IgG and IgM antibodies qualitatively through two optimized in-house ELISA and lateral flow immunoassay. Both approaches are based on the prokaryotic expression of 50 kDa SARS-CoV-2 recombinant nucleocapsid protein. This SARS-CoV-2rN-6×His was used either to coat ELISA plates or to be conjugated to gold nanoparticles followed by colorimetric detection of bound human IgG or IgM. In the LFA, we show the optimization of nanoparticle size, protein-binding capacity, membrane treatment, and finally testing the potential capacity of using either the optimized ELISA or LFA in detecting antibodies raised against viral infection. Assessment of both methods was carried out using human sera-positive and negative SARS-CoV-2 antibodies. The ELISA and LFA tests showed 86%, 96.5% sensitivity, 92%, 93.75% specificity, 97%, 98.2% PPV, and 64%, 88.2% NPV, respectively. In conclusion, both approaches were able to successfully detect human antibodies against SARS-CoV-2 nucleocapsid protein. The importance of both protocols cannot be overstated in the detection and diagnosis of viral infections, especially in developing countries.

Highly efficient cell-microbead encapsulation using dielectrophoresis-assisted dual-nanowell array.

Recent advancements in micro/nanofabrication techniques have led to the development of portable devices for high-throughput single-cell analysis through the isolation of individual target cells, which are then paired with functionalized microbeads. Compared with commercially available benchtop instruments, portable microfluidic devices can be more widely and cost-effectively adopted in single-cell transcriptome and proteome analysis. The sample utilization and cell pairing rate (∼33%) of current stochastic-based cell-bead pairing approaches are fundamentally limited by Poisson statistics. Despite versatile technologies having been proposed to reduce randomness during the cell-bead pairing process in order to statistically beat the Poisson limit, improvement of the overall pairing rate of a single cell to a single bead is typically based on increased operational complexity and extra instability. In this article, we present a dielectrophoresis (DEP)-assisted dual-nanowell array (ddNA) device, which employs an innovative microstructure design and operating process that decouples the bead- and cell-loading processes. Our ddNA design contains thousands of subnanoliter microwell pairs specifically tailored to fit both beads and cells. Interdigitated electrodes (IDEs) are placed below the microwell structure to introduce a DEP force on cells, yielding high single-cell capture and pairing rates. Experimental results with human embryonic kidney cells confirmed the suitability and reproducibility of our design. We achieved a single-bead capture rate of >97% and a cell-bead pairing rate of >75%. We anticipate that our device will enhance the application of single-cell analysis in practical clinical use and academic research.

Raspberry ketone improves non-alcoholic fatty liver disease induced in rats by modulating sphingosine kinase/sphingosine-1-phosphate and toll-like receptor 4 pathways.

OBJECTIVES: To investigate the therapeutic role of calorie-restricted diet (CR) and raspberry ketone (RK) in non-alcoholic fatty liver disease (NAFLD) and the implication of sphingosine kinase-1 (SphK1)/sphingosine-1-phosphate (S1P) and toll-like receptor 4 (TLR4) signalling. METHODS: NAFLD was induced by feeding rats high-fat-fructose-diet (HFFD) for 6 weeks. Rats were then randomly assigned to three groups (n = 6 each); NAFLD group continued on HFFD for another 8 weeks. CR group was switched to CR diet (25% calorie restriction) for 8 weeks and RK group was switched to normal diet and received RK (55 mg/kg/day; orally) for 8 weeks. Another six rats were used as normal control. KEY FINDINGS: HFFD induced a state of NAFLD indicated by increased fat deposition in liver tissue along with dyslipidemia, elevated liver enzymes, oxidative stress and inflammation. Either CR diet or RK reversed these changes and decreased HFFD-induced elevation of hepatic SphK1, S1P, S1PR1 and TLR4. Of notice, RK along with a normal calorie diet was even better than CR alone in most studied parameters. CONCLUSIONS: SphK1/S1P and TLR4 are interconnected and related to the establishment of HFFD-induced NAFLD and can be modulated by RK. Supplementation of RK without calorie restriction to patients with NAFLD unable to follow CR diet to achieve their treatment goals would be a promising therapeutic modality.

Sunitinib displays pulmonary fibrosis in experimental rats: Role of IL-17A dependent pathway.

Sunitinib (SUN) is an FDA approved first line drug for management of metastatic renal cancers and advanced cancerous states of gastrointestinal tract, however, side effects including fibrosis has been reported. Secukinumab (Secu) is an immunoglobulin G1 monoclonal antibody that exhibits anti-inflammatory activity by inhibiting several cellular signaling molecules. This study aimed to examine pulmonary protective potential of Secu in SUN-induced pulmonary fibrosis mediated through inhibition of inflammation via targeting IL-17A associated signaling pathway and using pirfenidone (PFD), an antifibrotic drug approved in 2014 for treatment of pulmonary fibrosis with IL-17A as one of its targets, as a reference drug. Wistar rats (160-200 g) were divided randomly into 4 groups (n = 6); Group 1 served as normal control; Group 2 served as disease control where it was exposed to SUN (25 mg/kg; 3 times weekly orally for 28 days); Group 3 was administered SUN and Secu (3 mg/kg subcutaneous at 0,14 and 28 days) and Group 4 was administered SUN and PFD (100 mg/kg/day orally for 28 days). Pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α were measured in addition to components of IL-17A signaling pathway (TGF-ß, collagen, hydroxyproline). Results revealed that IL-17A-associated signaling pathway was activated in fibrotic lung tissue induced by SUN. Relative to normal control, SUN administration significantly elevated lung organ coefficient, IL-1ß, IL-6, TNF-α, IL-17A, TGF-ß, hydroxyproline and collagen expression. Secu or PFD treatment restored the altered levels to nearly normal values. Our study indicates that IL-17A participates in the development and progression of pulmonary fibrosis in a TGF-ß dependent manner. Hence, components of IL-17A signaling pathway represent potential therapeutic targets for protection and treatment of fibro-proliferative lung disease.

Vanillin and pentoxifylline ameliorate isoproterenol-induced myocardial injury in rats via the Akt/HIF-1α/VEGF signaling pathway.

Myocardial infarction (MI) is a major health problem associated with high morbidity and mortality. Recently, angiogenesis has emerged as a novel therapeutic approach against ischemic diseases including MI. Therefore, we aimed to investigate the potential angiogenic effects of vanillin (Van) both alone and in combination with pentoxifylline (PTX), and to examine the molecular mechanisms through which Van and PTX may ameliorate cardiac injury induced in rats including their effects on oxidative stress, inflammation and apoptosis which play a key role in MI pathogenesis. MI was induced in rats using isoproterenol (ISO) (150 mg kg-1, SC, twice at a 24 h interval). Then, rats were treated orally with Van (150 mg kg-1 day-1), PTX (50 mg kg-1 day-1) or Van + PTX combination. ISO-induced cardiac injury was characterized by cardiac hypertrophy, ST-segment elevation and elevated serum levels of troponin-I, creatine kinase-MB and lactate dehydrogenase. Cardiac levels of the antioxidant markers GSH and SOD and the antiapoptotic protein Bcl-2 were decreased. On the other hand, cardiac levels of the oxidative stress marker malonaldehyde, the inflammatory cytokines TNF-α, IL-6 and IL-1ß, the proapoptotic protein Bax, and caspase-3 were increased. Moreover, the cardiac levels of p-Akt and HIF-1α and the mRNA expression levels of the angiogenic genes VEGF, FGF-2 and ANGPT-1 were increased. Treatment with either Van or PTX ameliorated ISO-induced changes and further upregulated Akt/HIF-1α/VEGF signaling. Furthermore, Van + PTX combination was more effective than monotherapy. These findings suggest a novel therapeutic potential of Van and PTX in ameliorating MI through enhancing cardiac angiogenesis and modulating oxidative stress, inflammation and apoptosis.