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To date, the epigenetic signature of preeclampsia (PE) is not completely deciphered. Oxidative stress-responsive long non-coding RNAs (lncRNAs) are deregulated in preeclamptic placenta; however, their circulating profiles and diagnostic abilities are still unexplored. We investigated serum redox-sensitive lncRNAs TUG1, H19, and NEAT1, and their target miR-29b/cystine/neutral/dibasic amino acids transporter solute carrier family 3, member 1 (SLC3A1) as potential non-invasive biomarkers of PE risk, onset, and severity. We recruited 82 patients with PE and 78 healthy pregnant women. We classified PE patients into early-onset (EOPE) and late-onset (LOPE) subgroups at a cut-off 34 gestational weeks and into severe and mild PE subgroups by blood pressure and proteinuria criteria. Bioinformatics analysis was employed to select lncRNAs/microRNA/target gene interactions. Serum H19, NEAT1, and SLC3A1 mRNA expression were reduced, meanwhile miR-29b levels were elevated, whereas there was no significant difference in TUG1 levels between PE patients and healthy pregnancies. Serum H19 levels were lower, whereas miR-29b levels were higher in EOPE versus LOPE. Serum miR-29b and H19 levels were higher in severe versus mild PE. ROC analysis identified serum H19, NEAT1, miR-29b, and SLC3A1 as potential diagnostic markers, with H19 (AUC = 0.818, 95%CI = 0.744–0.894) and miR-29b (AUC = 0.82, 95%CI = 0.755–0.885) were superior discriminators. Only H19 and miR-29b discriminated EOPE and severe PE cases. In multivariate logistic analysis, miR-29b and H19 were associated with EOPE, using maternal age and gestational age as covariates, while miR-29b was associated with severe PE, using maternal age as covariate. Studied markers were correlated with clinical and ultrasound data in the overall PE group. Serum H19 and TUG1 were negatively correlated with albuminuria in EOPE and LOPE, respectively. NEAT1 and SLC3A1 were correlated with ultrasound data in EOPE. Likewise, TUG1, miR-29b, and SLC3A1 showed significant correlations with ultrasound data in LOPE. Conclusively, this study configures SLC3A1 expression as a novel potential serum biomarker of PE and advocates serum H19 and miR-29b as biomarkers of EOPE and miR-29b as a biomarker of PE severity.

Abstract Background Yellow (stripe) rust of wheat, caused by Puccinia striiformis, is a serious disease that results in great economic losses. This study aimed to investigate the variation in plant responses in three wheat cultivars with different resistance levels against yellow rust. Results The highest disease severity was recorded for cv. Gemmieza-11 (95%), followed by cv. Shandweel 1 (60%), while the lowest was recorded for cv. Misr-3 (3%). qPCR results of the yellow rust-resistance genes Yr5, Yr10, Yr15, and Yr18 showed that the infection did not affect the expression of Yr5 and Yr15 in the infected Gemmieza-11 plants when compared to the non-infected control. In contrast, the infection significantly overexpressed Yr5 and Yr15 in cvs. Shandweel 1 and Misr-3. However, Misr-3 was superior in this regard, recording 3.85- and 4.07-fold for Yr5 and Yr15, respectively. In addition, the infection significantly upregulated Yr10 and Yr18 in the three tested cultivars, with the superiority for the cultivar Misr-3, followed by Shandweel 1. Activity of the antioxidant enzymes peroxidase, polyphenol oxidase, and catalase was significantly higher in the infected plants of cv. Misr-3 than in cv. Shandweel-1, while the lowest values were recorded in cv. Gemmieza-11. The increment in this activity was associated with a reduction in the lipid peroxidation in the three tested cultivars. The phenolic content considerably increased also upon infection in cv. Misr-3 followed by Shandweel-1 but not in cv. Gemmieza-11, compared to the non-infected plants. Transmission electron microscopy demonstrated that the infected mesophyll cells in cv. Gemmieza-11 showed abnormalities in the chloroplasts and thick-walled haustoria. On the contrary, the mesophyll cells in cv. Misr-3 showed no haustoria and well organized chloroplasts. The mesophyll cells in cv. Shandweel-1 displayed highly degenerated haustoria, a degenerated granulated cytoplasm, and a thick host cell wall, indicating intermediate defense responses against the invading pathogen. Plant growth, yield, and photosynthetic pigments were higher in cv. Misr-3, followed by cv. Shandweel-1, and the lowest values were recorded in cv. Gemmieza-11. Conclusions The obtained results displayed that Yr5 and Yr15 were more effective than Yr10 and Yr18, indicating their main roles in regulating multiple defense mechanisms and hypersensitive responses.

Abstract COVID-19 has been a growing global concern in the past four years. Several syndromes associated with this multi-organ viral infection have been observed since the outbreak. According to estimates, 10–15% of people with SARS-CoV- infection may have post-COVID-19 syndrome. Even months after infection, common residual signs and symptoms include myalgia, exhaustion, shortness of breath, rapid heartbeat, stroke, and memory and cognitive impairment which can negatively affect survivors’ quality of life and may consequently lead to their death. Therefore, it is necessary to think about potential therapy options for dealing with both short and long-term impacts. Paracetamol (a common analgesic and antipyretic) and Dexketoprofen Trometamol (a non-steroidal anti-inflammatory drug) are used together to relieve post-COVID symptoms like myalgia (muscle pain) and headache. Additionally, to prevent thrombotic events, Rivaroxaban is recommended for 35 days following discharge. Thus an eco-friendly HPLC-DAD technique was developed for simultaneous quantification of Paracetamol, Dexketoprofen Trometamol, and Rivaroxaban which are co-administered for treatment of post-COVID-19 syndrome. The suggested method was found to be linear in the concentration ranges of 3.00–45.00 µg/mL, 0.5–50.00 µg/mL, and 0.15–20.00 µg/mL, and a limit of detection down to 0.531 µg/mL, 0.095 µg/mL and 0.047 µg/mL for Paracetamol, Dexketoprofen Trometamol and Rivaroxaban, respectively. This method was effectively used to quantify the studied drugs in their bulk powder and spiked human plasma with high percentage recoveries (96.55–99.46%). The suggested approach was validated per International Conference on Harmonization (ICH) requirements and found to be within the acceptable ranges. The method was developed using Green Analytical Chemistry (GAC) principles, with the solvents used and run time having a significant effect on the method’s greenness. “Non-toxic” ethanol served as the organic modifier in the mobile phase, moreover, the total run time was 12 min making it suitable for the routine analysis of the mentioned drugs in plasma samples. To get a full image of the method’s greenness profile; two most recent greenness assessment tools, the Green Analytical Procedure Index (GAPI), and the Analytical GREEnness metric (AGREE), were employed, with White Analytical Chemistry (WAC) principles proving its environmental safety.

Abstract Tulathromycin (TUL) is a widely used veterinary antibiotic for treating bovine and porcine respiratory infections. Consuming animal-derived food contaminated with this medication may jeopardize human health. This work adopted the first portable potentiometric platform for direct TUL sensing in pharmaceutical and food products. The sensor employed a plasticized PVC membrane on a glassy carbon electrode doped with calix[6]arene and multi-walled carbon nanotubes (MWCNT) in a single solid contact layer for selective binding and signal stability. Characterization via scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) confirmed the material’s integrity. The MWCNT-based sensor produced a stable Nernstian response (1.0 × 10−7 to 1.0 × 10−3 M) and a limit of detection (LOD) of 9.76 × 10–8 M with instantaneous response (8 ± 2 s). IUPAC validation revealed high selectivity for TUL against interfering ions, minimal drift (0.6 mV/h), and functionality over a broad pH range (2.0–7.0), allowing direct application to dosage form, spiked milk, and liver samples. Eco-Scale, AGREE, and Whiteness assessment proved the method's ecological sustainability, economic viability, and practical feasibility, surpassing traditional approaches. Graphical Abstract

Background and Objectives: Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the world. Due to failure of the traditional drugs to produce a complete cure for AD, the search for new safe and effective lines of therapy has attracted the attention of ongoing research. Canagliflozin is an anti-diabetic agent with proven efficacy in the treatment of neurological disorders in which mitochondrial dysfunction, oxidative stress, apoptosis, and autophagy play a pathophysiological role. Elucidation of the potential effects of different doses of canagliflozin on AD induced by aluminium chloride in rats and exploration of the molecular mechanisms that may contribute to these effects were the primary objectives of the current study. Materials and Methods: In a rat model of AD, the effect of three different doses of canagliflozin on the behavioural, biochemical, and histopathological alterations induced by aluminium chloride was assessed. Results: Canagliflozin administered to aluminium chloride-treated animals induced dose-dependent normalisation in the behavioural tests, augmentation of the antioxidant defence mechanisms, inhibition of TXNIP/NLRP3 inflammasome signalling, modulation of the SIRT1/HMGB1 axis, interference with the pro-inflammatory and the pro-apoptotic mechanisms, and restoration of the mitochondrial functions and autophagy in the hippocampal tissues to approximately baseline values. In addition, canagliflozin exhibited an interesting dose-dependent ability to repress aluminium chloride-induced histopathological changes in the brain. Conclusions: The effects of canagliflozin on oxidative stress, mitochondrial functions, inflammatory pathways, and autophagy signals may open new gates towards the mitigation of the pathologic features of AD.

Background and Objectives: Parkinson’s disease (PD) is a pathological state characterized by a combined set of abnormal movements including slow motion, resting tremors, profound stiffness of skeletal muscles, or obvious abnormalities in posture and gait, together with significant behavioral changes. Until now, no single therapeutic modality was able to provide a complete cure for PD. This work was a trial to assess the immunomodulatory effects of canagliflozin with or without levodopa/carbidopa on rotenone-induced parkinsonism in Balb/c mice. Materials and Methods: In a mouse model of PD, the effect of canagliflozin with or without levodopa/carbidopa was assessed at the behavioral, biochemical, and histopathological levels. Results: The combination of levodopa/carbidopa and canagliflozin significantly mitigated the changes induced by rotenone administration regarding the behavioral tests, striatal dopamine, antioxidant status, Nrf2 content, SIRT–1/PPAR–gamma axis, RAGE/HMGB1/NF-κB signaling, and mitochondrial dysfunction; abrogated the neuroinflammatory responses, and alleviated the histomorphologic changes induced by rotenone administration relative to the groups that received either levodopa/carbidopa or canagliflozin alone. Conclusions: Canagliflozin may represent a new adjuvant therapeutic agent that may add value to the combatting effects of levodopa/carbidopa against the pathological effects of PD.

Abstract As a GABA-β receptor agonist, the central muscle relaxant Baclofen (BAC) has a potential of abuse. Unfortunately, the sense of wellbeing and pleasure is obtained at very high BAC doses. This is associated with many life-threating or even fatal cases due to neurological and respiratory failures. Moreover, having narrow therapeutic index makes BAC a high-risk drug. This is potentiated in case of long-treatment regimen or off-label use in smoking and alcohol cessation protocols. Until now, there is no rapid diagnostic test available for BAC screening. Therefore; It is quite difficult to routinely monitor cases on BAC regimen. On the other hand, smartphone-based colorimetric point of care testing (POCT) is displacing conventional analytical approaches in the detection and assay of abused drugs as well as therapeutic drug monitoring. It offers on-site, rapid, easy, affordable and interpretable analysis. Incorporating smartphone as a portable device facilitates its application, especially in remote areas and low-income countries. For the first time, the current work presents a smartphone-based colorimetric POCT for BAC analysis in urine without interference from urine matrix. It depends on BAC reaction with naphthoquinone sulfonate (NQS) in highly alkaline aqueous medium. The developed color was captured in a customized photo box using smartphone camera. Then, intensity of the blue channel was measured by a software application “Color Analyzer”. All parameters were optimized with respect to the colorimetric reaction, photographing and smartphone-based analysis. All parameters were successfully investigated according to FDA guidelines for bioanalytical method validation. Also, all POCT criteria were considered as per WHO requirements. This method could determine BAC, linearly, from 0.02 to 0.21 mmol L−1 in urine. Moreover, LLOQ was lower than the expected BAC therapeutic concentrations in urine. The proposed method proved high reliability and suitability to analyze BAC in urine. This strongly recommends its routine application in screening BAC abusers and BAC therapeutic monitoring. Graphical Abstract

The reproductive system of males is adversely impacted by lead (Pb), a toxic heavy metal. The present study examined arbutin, a promising hydroquinone glycoside, for its potential ameliorative impact against Pb-induced testicular impairment in rats. The testicular injury was induced by the intraperitoneal administration of Pb acetate (20 mg/kg/day) for 10 consecutive days. Thirty-six rats were divided into six experimental groups (n = 6 per group): control, control treated with oral arbutin (250 mg/kg), control treated with intraperitoneal arbutin (75 mg/kg), untreated Pb, Pb treated with oral arbutin, and Pb treated with intraperitoneal arbutin. The treatments were administered daily for 10 days. Arbutin was administered by the oral and intraperitoneal routes to compare the efficacy of both routes in mitigating Pb acetate-induced testicular dysfunction. The current data revealed that both oral and intraperitoneal administration of arbutin significantly enhanced serum testosterone and sperm count/motility, indicating the amelioration of testicular dysfunction. In tandem, both routes lowered testicular histopathological aberrations and Johnsen’s damage scores. These favorable outcomes were driven by dampening testicular oxidative stress, evidenced by lowered lipid peroxidation and increased glutathione and catalase antioxidants. Moreover, arbutin lowered testicular p-JAK2 and p-STAT3 levels, confirming the inhibition of the JAK2/STAT3 pro-inflammatory pathway. In tandem, arbutin suppressed the testicular NLRP3/caspase-1/NF-B axis and augmented the cytoprotective PK2/PKR2 pathway. Notably, intraperitoneal arbutin at a lower dose prompted a more pronounced mitigation of Pb-induced testicular dysfunction compared to oral administration. In conclusion, arbutin ameliorates Pb-evoked testicular damage by stimulating testicular antioxidants and the PK2/PKR2 pathway and inhibiting the JAK2/STAT3 and NLRP3/caspase-1 pro-inflammatory pathways. Hence, arbutin may be used as an adjunct agent for mitigating Pb-induced testicular impairment.

Abstract Background Stripe rust is considered one of the most devastating diseases of wheat all over the world, resulting in a high loss in its production. In this study, time-course changes in expression of the polyphenol biosynthesis pathways genes in wheat against stripe rust were investigated. The defense mechanisms triggered by mycorrhizal colonization and/or spraying with Streptomyces viridosporus HH1 against this disease were also investigated. Results Results obtained revealed that C3H, which is considered the key gene in lignin biosynthesis, was the most expressed gene. Furthermore, most of the chlorogenic acid and flavonoid biosynthesis genes were also overexpressed. Volcano plots of the studied genes reveal that the dual treatment led to a high significant overexpression of 10 out of the 13 studied genes. Heatmap of these genes showed that the most frequent expressed gene in response to all applied treatments along the study period was DFR, the key gene in the biosynthesis of anthocyanidins. Gene co-expression network of the studied genes showed that HQT was the most central gene with respect to the other genes, followed by AN2 and DFR, respectively. Accumulation of different flavonoids and phenolic acids were detected in response to the dual treatment, in particular, cinnamic acid, coumarin, and esculetin, which recorded the highest elevation level recording 1000, 488.23, and 329.5% respectively. Furthermore, results from the greenhouse experiment showed that application of the dual treatment led to an 82.8% reduction in the disease severity, compared with the control treatment. Conclusions We can conclude that the biosynthesis of lignin, chlorogenic acid, and flavonoids contributed to the synergistic triggering effect of the dual treatment on wheat resistance to stripe rust.

The study of thermal therapy to tumors and the response of living cells to this therapy used to treat tumor is very important due to the complexity of heat transfer in biological tissues. In the past few years, there has been a growing interest among clinicians, mathematicians, and engineers regarding the use of computational and mathematical methods to simulate biological systems. Numerous medical proceedings also employ mathematical modeling and engineering techniques as a means to guarantee their safety and evaluate the associated risks effectively. This manuscript provides an analytical solution used for the first time to study the mechanism of biological thermal response during heat therapy on spheroidal skin tumor. The proposed method used a generalized thermoelasticity model with one relaxation time. The influence of relaxation times on the responses of diseased and healthy tissues is studied and interpreted graphically. Also, the impact of different laser irradiance on the thermal profile of the malignant tumor cells over a period of 2 minutes is interpreted graphically. To investigate the transfer of heat within biological tissues during the thermal therapy, the Laplace transform and inverse Laplace transform methods were applied. A comparison of the present generalized thermoelasticity model and different models based on Pennes bioheat transfer PBT shows that our proposed model yields more realistic and accurate predictions. The current model can be used to explain various therapeutic methods.

Abstract Background Plasmopara viticola, the causal agent of grape downy mildew, is one of the most serious grape diseases. Application of Trichoderma harzianum grown on different potato dextrose supplemented broth media using some chemical inducers (TSDCIS), i.e., thiamine (T2), a mixture of micronutrients (T3) and potassium tartrate (T4), compared to Trichoderma without amendment (T1), was conducted under field conditions to evaluate the potential of T. harzianum against grape downy mildew, improving the growth, as well as the yield quality, and quantity. Results Foliar application of all TSDCIS significantly reduced the disease severity and increased the phenolic content, peroxidase, polyphenol oxidase enzyme activity, growth parameters, and yield parameters. Trichoderma growing on medium supplemented with potassium tartrate (T4) achieved the most significant reduction in the disease severity (78.9, 81.8%) than the control treatment in two growing seasons, respectively. In contrast, it decreased H2O2 content, lipid peroxidation, and cellular electrolyte leakage. Scanning electron microscopy observations revealed that the number of opened stomata, average stomatal area, and stomatal pore area decreased significantly in response to T4 treatment. Conclusions It can be concluded that using Trichoderma growing on medium supplemented with potassium tartrate (T4) to biosafety control the downy mildew disease of grape and improve its growth, yield, and fruit quality is recommended.

Abstract Two thin layer chromatography (TLC) methods have been developed for the determination of pesticides residues of imidacloprid (IMD) and deltamethrin (DLM) in thyme and guava leaves. In the two methods, the used stationary phase was silica gel 60 F254 plates impregnated in chitosan nanoparticles (ChTNPs) 0.5% to improve separation using a green developing system consists of isopropyl alcohol for IMD and n-hexane-toluene-ethylacetate for DLM. The two pesticides were determined quantitatively, after TLC separation, at wavelengths 270.0 nm for IMD and 230.0 nm for DLM. Validation of both approaches was carried out in agreement with the guidelines of International Conference on Harmonization (ICH) and found to be selective, reliable and reproducible. Limits of detection of IMD and DLM were 0.002 and 0.00116 μg/spot, respectively. The newly developed TLC methods were used to monitor the pre-harvest interval estimation. Analytical eco-scaling depending on penalty points for IMD was calculated and showed that this method was eco-friendlier than the reported one. Graphical Abstract

Despite being an effective chemotherapeutic agent, the clinical use of doxorubicin (DOX) is limited by several organ toxicities including hepatic injury. Pentoxifylline (PTX) is a methylxanthine derivative with marked anti-inflammatory and anti-apoptotic features. It is unknown, however, whether PTX can mitigate DOX-evoked hepatotoxicity. This study aims to explore the potential hepatoprotective impact of PTX in DOX-induced hepatic injury and the underlying molecular mechanisms. Histopathology, immunohistochemistry, and ELISA were used to examine liver tissues. The current findings revealed that PTX administration to DOX-intoxicated rats mitigated the pathological manifestations of hepatic injury, reduced microscopical damage scores, and improved serum ALT and AST markers, revealing restored hepatic cellular integrity. These favorable effects were attributed to PTX’s ability to mitigate inflammation by reducing hepatic IL-1β and TNF-α levels and suppressing the pro-inflammatory HMGB1/TLR4/NF-κB axis. Moreover, PTX curtailed the hepatic apoptotic abnormalities by suppressing caspase 3 activity and lowering the Bax/Bcl-2 ratio. In tandem, PTX improved the defective autophagy events by lowering hepatic SQSTM-1/p62 accumulation and enhancing the AMPK/mTOR pathway, favoring autophagy and hepatic cell preservation. Together, for the first time, our findings demonstrate the ameliorative effect of PTX against DOX-evoked hepatotoxicity by dampening the hepatic HMGB1/TLR4/NF-κB pro-inflammatory axis and augmenting hepatic AMPK/mTOR-driven autophagy. Thus, PTX could be utilized as an adjunct agent with DOX regimens to mitigate DOX-induced hepatic injury.

Context Parapneumonic effusion and empyema are commonly encountered by the pulmonologist. The decision regarding management is still challenging. Aim To compare outcomes of intrapleural streptokinase with pigtail catheter drainage versus medical thoracoscopy in complicated parapneumonic effusion. Methods and material Forty patients with complicated parapneumonic effusion were randomly allocated to one of two groups. Twenty patients underwent streptokinase intrapleural instillation via pigtail catheter. The other twenty patients underwent medical thoracoscopy. Results Intrapleural streptokinase instillation procedure was significantly shorter duration (12.80 ± 3.05 min) than medical thoracoscopy procedure (25.26 ± 4.66 min). However medical thoracoscopy showed a significant less days required to remove the drainage system (5.80 ± 1.70 days) versus intrapleural streptokinase instillation procedure (9.40 ± 3.91 days). Both groups had no significant complications. Lung expansion was achieved in 90% of patients treated with intrapleural streptokinase instillation and in 95% of patients treated with a medical thoracoscopy technique, with no statistically significant difference between the two groups. Conclusions Treatment of complicated parapneumonic effusions is undeniably interdisciplinary. Both intrapleural streptokinase with pigtail catheter drainage and medical thoracoscopy are safe and improve outcomes in complicated parapneumonic effusion. Medical thoracoscopy has an advantage of fewer days required for tube withdrawal. Pigtail insertion has an advantage of shorter procedure time compared to medical thoracoscopy

Two spectrometric methods and a TLC-densitometric method are described for the determination of hyoscine/ketoprofen combination. A new spectrophotometric method called the co-absorptive point has been explained based on the idea of the isosbestic point. This method has been introduced to resolve the overlapped spectra and the challenging drug ratios found in the mentioned dosage form. Also, a dual wavelength technique measuring at 208.4 and 218.2 nm was explained. In the two spectrometric techniques, ketoprofen was determined by zero-order spectra, while hyoscine was determined by co-absorptive point and dual wavelength techniques with linearity ranges of 8-100 and 8-70 [micro]g/mL. In the TLC-densitometric method, the developing phase was methanol-ethyl acetate-ammonia (35 : 65 : 5, v/v) with linearity ranges of 1-20 and 5-25 [micro]g/mL for hyoscine and ketoprofen, respectively. The greenness of the described techniques was assessed according to the eco-scale and compared to previously reported methods., Author(s): Khadiga M. Kelani [sup.1] [sup.2], Mamdouh R. Rezk [sup.1], Ahmed S. Saad [sup.1] [sup.3], Menna S. ElSherbiny [sup.2], Hany H. Monir [sup.1] Author Affiliations: (1) grid.7776.1, 0000 0004 0639 [...]

Background and Objectives: Alzheimer's disease (AD) is the most common neurodegenerative disorder in the world. Due to failure of the traditional drugs to produce a complete cure for AD, the search for new safe and effective lines of therapy has attracted the attention of ongoing research. Canagliflozin is an anti-diabetic agent with proven efficacy in the treatment of neurological disorders in which mitochondrial dysfunction, oxidative stress, apoptosis, and autophagy play a pathophysiological role. Elucidation of the potential effects of different doses of canagliflozin on AD induced by aluminium chloride in rats and exploration of the molecular mechanisms that may contribute to these effects were the primary objectives of the current study. Materials and Methods: In a rat model of AD, the effect of three different doses of canagliflozin on the behavioural, biochemical, and histopathological alterations induced by aluminium chloride was assessed. Results: Canagliflozin administered to aluminium chloride-treated animals induced dose-dependent normalisation in the behavioural tests, augmentation of the antioxidant defence mechanisms, inhibition of TXNIP/NLRP3 inflammasome signalling, modulation of the SIRT1/HMGB1 axis, interference with the pro-inflammatory and the pro-apoptotic mechanisms, and restoration of the mitochondrial functions and autophagy in the hippocampal tissues to approximately baseline values. In addition, canagliflozin exhibited an interesting dose-dependent ability to repress aluminium chloride-induced histopathological changes in the brain. Conclusions: The effects of canagliflozin on oxidative stress, mitochondrial functions, inflammatory pathways, and autophagy signals may open new gates towards the mitigation of the pathologic features of AD. [ABSTRACT FROM AUTHOR]

In this manuscript, the generalized thermoporoelasticity theory is modified by using fractional derivatives. The revised equation is used to study mathematical model for two-dimensional problem subjected to a known heat source among the context of the fractional order generalized thermo-poroelasticity theory. An analytical solution using Laplace transform is followed to address the governing equations. Problem for porous infinitely Cylinder for certain boundary conditions is solved by the resulting formulation. Numerical effects are represented graphically and discussed. Some comparisons are shown in figures to estimate the impact of porosity ( $ 0 \le \beta \le 1 $ 0 ≤ β ≤ 1) and fractional parameter $ (0 \le \alpha \le 1) $ (0 ≤ α ≤ 1). Porosity has a pronounced effect on the speed, the pressure but has a weak effect on the temperatures. Comparison is done with a porous infinitely long Cylinder with the identical configuration in case of the absence of the fluid. The presented results in this issue are of great important in many science and engineering applications. Issues in cylindrical regions are important because of their several applications in producing of machine components. The theory of fractional calculus has been used successfully to model polymers materials. The result provides a motivation to investigate thermoelastic materials as a new class of applicable materials. [ABSTRACT FROM AUTHOR]

Background and Objectives: Parkinson's disease (PD) is a pathological state characterized by a combined set of abnormal movements including slow motion, resting tremors, profound stiffness of skeletal muscles, or obvious abnormalities in posture and gait, together with significant behavioral changes. Until now, no single therapeutic modality was able to provide a complete cure for PD. This work was a trial to assess the immunomodulatory effects of canagliflozin with or without levodopa/carbidopa on rotenone-induced parkinsonism in Balb/c mice. Materials and Methods: In a mouse model of PD, the effect of canagliflozin with or without levodopa/carbidopa was assessed at the behavioral, biochemical, and histopathological levels. Results: The combination of levodopa/carbidopa and canagliflozin significantly mitigated the changes induced by rotenone administration regarding the behavioral tests, striatal dopamine, antioxidant status, Nrf2 content, SIRT–1/PPAR–gamma axis, RAGE/HMGB1/NF-κB signaling, and mitochondrial dysfunction; abrogated the neuroinflammatory responses, and alleviated the histomorphologic changes induced by rotenone administration relative to the groups that received either levodopa/carbidopa or canagliflozin alone. Conclusions: Canagliflozin may represent a new adjuvant therapeutic agent that may add value to the combatting effects of levodopa/carbidopa against the pathological effects of PD. [ABSTRACT FROM AUTHOR]