Retinoic acid attenuates ischemic injury-induced activation of glial cells and inflammatory factors in a rat stroke model.

Stroke is a leading cause of death and long-term disability which can cause oxidative damage and inflammation of the neuronal cells. Retinoic acid is an active metabolite of vitamin A that has various beneficial effects including antioxidant and anti-inflammatory effects. In this study, we investigated whether retinoic acid modulates oxidative stress and inflammatory factors in a stroke animal model. A middle cerebral artery occlusion (MCAO) was performed on adult male rats to induce focal cerebral ischemia. Retinoic acid (5 mg/kg) or vehicle was injected into the peritoneal cavity for four days before MCAO surgery. The neurobehavioral tests were carried out 24 h after MCAO and cerebral cortex tissues were collected. The cortical damage was assessed by hematoxylin-eosin staining and reactive oxygen species assay. In addition, Western blot and immunohistochemical staining were performed to investigate the activation of glial cells and inflammatory cytokines in MCAO animals. Ionized calcium-binding adapter molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) were used as markers of microglial and astrocyte activation, respectively. Tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were used as representative pro-inflammatory cytokines. Results showed that MCAO damage caused neurobehavioral defects and histopathological changes in the ischemic region and increased oxidative stress. Retinoic acid treatment reduced these changes caused by MCAO damage. We detected increases in Iba-1 and GFAP in MCAO animals treated with vehicle. However, retinoic acid alleviated increases in Iba-1 and GFAP caused by MCAO damage. Moreover, MCAO increased levels of nuclear factor-κB and pro-inflammatory cytokines, including TNF-α and IL-1ß. Retinoic acid alleviated the expression of these inflammatory proteins. These findings elucidate that retinoic acid regulates microglia and astrocyte activation and modulates pro-inflammatory cytokines. Therefore, this study suggests that retinoic acid exhibits strong antioxidant and anti-inflammatory properties by reducing oxidative stress, inhibiting neuroglia cell activation, and preventing the increase of pro-inflammatory cytokines in a cerebral ischemia.

Explainable AI for Material Property Prediction Based on Energy Cloud: A Shapley-Driven Approach.

The scientific community has raised increasing apprehensions over the transparency and interpretability of machine learning models employed in various domains, particularly in the field of materials science. The intrinsic intricacy of these models frequently results in their characterization as "black boxes", which poses a difficulty in emphasizing the significance of producing lucid and readily understandable model outputs. In addition, the assessment of model performance requires careful deliberation of several essential factors. The objective of this study is to utilize a deep learning framework called TabNet to predict lead zirconate titanate (PZT) ceramics' dielectric constant property by employing their components and processes. By recognizing the crucial importance of predicting PZT properties, this research seeks to enhance the comprehension of the results generated by the model and gain insights into the association between the model and predictor variables using various input parameters. To achieve this, we undertake a thorough analysis with Shapley additive explanations (SHAP). In order to enhance the reliability of the prediction model, a variety of cross-validation procedures are utilized. The study demonstrates that the TabNet model significantly outperforms traditional machine learning models in predicting ceramic characteristics of PZT components, achieving a mean squared error (MSE) of 0.047 and a mean absolute error (MAE) of 0.042. Key contributing factors, such as d33, tangent loss, and chemical formula, are identified using SHAP plots, highlighting their importance in predictive analysis. Interestingly, process time is less effective in predicting the dielectric constant. This research holds considerable potential for advancing materials discovery and predictive systems in PZT ceramics, offering deep insights into the roles of various parameters.

Neuroprotective effects of chlorogenic acid by controlling the Bcl-2 family protein in a stroke animal model.

Ischemic stroke causes severe brain damage and high mortality. Chlorogenic acid is a phenolic compound that has neuroprotective properties. B-cell lymphoma-2 (Bcl-2) family proteins are important for apoptosis regulation. Bcl-2 and Bcl-xL are proteins that inhibit apoptosis, and Bax and Bad induce apoptosis. In this study, we investigated whether chlorogenic acid exerts a neuroprotective effect against ischemic stroke damage by regulating Bcl-2 family proteins. We performed middle cerebral artery occlusion (MCAO) to induce ischemic stroke in adult male rats. The animals were intraperitoneally injected with normal saline as a vehicle or chlorogenic acid (30 mg/kg) 2 hr after MCAO. Cerebral cortex tissue was collected 24 hr after MCAO damage. MCAO damage caused histopathological changes and increased the number of terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling-positive cells, while chlorogenic acid attenuated these changes. RT-qPCR and Western blot results showed decreases in Bcl-2 and Bcl-xL expression and an increase in Bax and Bad expression in MCAO animals. However, chlorogenic acid treatment attenuated these changes due to MCAO damage. The interaction of Bax with Bcl-2 or Bcl-xL decreased in MCAO animals, and the binding of Bad with Bcl-2 or Bcl-xL increased. However, chlorogenic acid treatment reduced these changes. Chlorogenic acid also prevented MCAO-induced increases in caspase-3 and caspase-9 expression. This study provides evidence that chlorogenic acid has neuroprotective effects against MCAO damage by modulating Bcl-2 family proteins including Bcl-2, Bcl-xL, Bax, and Bad. Furthermore, chlorogenic acid regulates the interaction between Bcl-2 family proteins. In conclusion, chlorogenic acid contributes to neuroprotection against ischemic stroke damage by controlling Bcl-2 family proteins.

Identification of proteins regulated by chlorogenic acid in an ischemic animal model: a proteomic approach.

BACKGROUND: Cerebral ischemia is a serious neurological disorder that can lead to high morbidity and mortality. Chlorogenic acid is a polyphenol compound with antioxidant that can regulate proteins in cerebral ischemia. Middle cerebral artery occlusion (MCAO) surgery was performed to induce ischemic brain injury and was maintained for 24 h. Chlorogenic acid (30 mg/kg) or vehicle was administrated into the peritoneal cavity 2 h after MCAO surgery. The cerebral cortical tissues were collected for further study and a proteomic approach was performed to identify the proteins changed by chlorogenic acid in the MCAO animals. RESULTS: We found that chlorogenic acid alleviated in changes in adenosylhomocysteinase, glycerol-3-phosphate dehydrogenase, eukaryotic translation initiation factor 4A-II, apolipoprotein A-I, and mu-crystallin. These proteins were reduced in MCAO animals with vehicle, and these reductions were attenuated by chlorogenic acid treatment. The mitigation of this reduction by chlorogenic acid was confirmed by the reverse transcription PCR technique. These proteins are associated with energy metabolism, protein synthesis, inflammation, and physiological metabolism. They are involved in the neuroprotective effect of chlorogenic acid. These results showed that chlorogenic acid alleviates the neurological disorders caused by MCAO and regulates the expression of proteins involved in neuroprotection. CONCLUSIONS: Therefore, our findings provide evidence that chlorogenic acid plays a neuroprotective role in stroke animal models by controlling specific proteins.

Unveiling Lathyrus aphaca L. as a Newly Identified Host for Begomovirus Infection: A Comprehensive Study.

The Begomovirus genus of the family Geminiviridae comprises the largest group of geminiviruses. Begomoviruses are transmitted by the whitefly complex (Bemisia tabaci) and infect dicotyledonous plants in tropical and subtropical regions. The list of begomoviruses is continuously increasing as a result of improvements in the methods for identification, especially from weed plants, which are considered a source of new viruses and reservoirs of economically important viruses but are often neglected during diversity studies. Lathyrus aphaca L. weed plants (yellow-flowered pea) with varicose veins and discoloration of the leaves were found. Amplified genomic DNA through rolling circular amplification was subjected to PCR analysis for the detection of the viral genome and associated DNA-satellites (alphasatellites and betasatellites). A full-length sequence (2.8 kb) of a monopartite begomovirus clone was determined; however, we could not find any associated DNA satellites. The amplified full-length clone of Rose leaf curl virus (RoLCuV) reserved all the characteristics and features of an Old World (OW) monopartite begomovirus. Furthermore, it is the first time it has been reported from a new weed host, yellow-flowered pea. Rolling circle amplification and polymerase chain reaction analysis of associated DNA satellites, alphasatellite, and betasatellite, were frequently accomplished but unable to amplify from the begomovirus-infected samples, indicating the presence of only monopartite Old World begomovirus. It is observed that RoLCuV has the capability to infect different hosts individually without the assistance of any DNA satellite component. Recombination in viruses is also a source of begomovirus infection in different hosts.

Phenotypic Classification of Eye Colour and Developmental Validation of the Irisplex System on Population Living in Malakand Division, Pakistan.

The core objective of forensic DNA typing is developing DNA profiles from biological evidence for personal identification. The present study was designed to check the validation of the IrisPlex system and the Prevalence of eye colour in the Pakhtoon population residing within the Malakand Division. METHODS: Eye colour digital photographs and buccal swab samples of 893 individuals of different age groups were collected. Multiplexed SNaPshot single base extension chemistry was used, and the genotypic results were analysed. Snapshot data were used for eye colour prediction through the IrisPlex and FROG-kb tool. RESULTS: The results of the present study found brown eye colour to be the most prevalent eye colour in comparison to intermediate and blue coloured. Overall, individuals with brown-coloured eyes possess CT (46.84%) and TT (53.16%) genotypes. Blue eye-coloured individuals are solely of the CC genotype, while individuals of intermediate eye colour carry CT (45.15%) and CC (53.85%) genotypes in rs12913832 SNP in the HERC2 gene. It was also revealed that brown-coloured eyes individuals were dominant among all age groups followed by intermediate and blue. Statistical analysis between particular variables and eye colour showed a significant p-value (<0.05) for rs16891982 SNP in SLC45A2 gene, rs12913832 SNP in HERC2 gene, rs1393350 SNP in SLC45A2, districts and gender. The rest of the SNPs were non-significant with eye colour, respectively. The rs12896399 SNP and SNP rs1800407 were found significant with rs16891982 SNP. The result also demonstrated that the study group differs from the world population based on eye colour. The two eye colour prediction results were compared, and it was discovered that IrisPlex and FROG-Kb had similar higher prediction ratios for Brown and Blue eye colour. CONCLUSIONS: The results of the current study revealed brown eye colour to be the most prevalent amongst members of the local population of Pakhtoon ethnicity in the Malakand Division of northern Pakistan. A set of contemporary human DNA samples with known phenotypes are used in this research to evaluate the custom panel's prediction accuracy. With the aid of this forensic test, DNA typing can be supplemented with details about the appearance of the person from whom the sample was taken in cases involving missing persons, ancient human remains, and trace samples. This study may be helpful for future population genetics and forensics studies.

Novel Synthesis of CuO/GO Nanocomposites and Their Photocatalytic Potential in the Degradation of Hazardous Industrial Effluents.

Photocatalytic degradation of dyes has been the subject of extensive study due to its low cost, eco-friendly operation, and absence of secondary pollutants. Copper oxide/graphene oxide (CuO/GO) nanocomposites are emerging as a new class of fascinating materials due to their low cost, nontoxicity, and distinctive properties such as a narrow band gap and good sunlight absorbency. In this study, copper oxide (CuO), graphene oxide (GO), and CuO/GO were synthesized successfully. X-ray diffractometer (XRD) and Fourier transform infrared (FTIR) spectroscopy confirm the oxidation and production of GO from the graphene of lead pencil. According to the morphological analysis of nanocomposites, CuO nanoparticles of sizes ≤20 nm on the GO sheets were evenly adorned and distributed. Nanocomposites of different CuO:GO ratios (1:1 up to 5:1) were applied for the photocatalytic degradation of methyl red (MR). CuO:GO(1:1) nanocomposites achieved 84% MR dye removal, while CuO:GO(5:1) nanocomposites achieved the highest value (95.48%). The thermodynamic parameters of the reaction for CuO:GO(5:1) were evaluated using the Van't Hoff equation and the activation energy was found to be 44.186 kJ/mol. The reusability test of the nanocomposites showed high stability even after seven cycles. CuO/GO catalysts can be used in the photodegradation of organic pollutants in wastewater at room temperature due to their excellent properties, simple synthesis process, and low cost.

Epigallocatechin gallate restores the reduction of protein phosphatase 2 A subunit B caused by middle cerebral artery occlusion.

BACKGROUND: Epigallocatechin gallate (EGCG) is a flavonoid compound commonly found in green tea. It exhibits antioxidant, anti-inflammatory, and neuroprotective effects in cerebral ischemia. Protein phosphatase 2 A (PP2A) is an important serine/threonine phosphatase enzyme involved in various cellular activities. PP2A subunit B is present abundantly in the brain and plays an important role in the nervous system. We investigated the effect of EGCG on the expression level of PP2A subunit B in cerebral ischemia caused by middle cerebral artery occlusion (MCAO). EGCG (50 mg/kg) or vehicle was injected into the peritoneal cavity prior to MCAO surgery. Neurological behavior tests were performed 24 h after MCAO, and right cerebral cortex tissue was collected. Cerebral ischemia caused serious neurological abnormalities, which were alleviated by EGCG administration. We screened the expression of PP2A subunits containing A, B, and C using reverse-transcription PCR. We confirmed that PP2A subunit B exhibited significant changes in MCAO animals compared to subunits A and C. We continuously examined the expression of PP2A subunit B protein in MCAO animals using Western blot analysis. RESULTS: EGCG alleviated the reduction of PP2A subunit B protein by MCAO damage. In addition, immunohistochemistry demonstrated a decrease in the number of PP2A subunit B-positive cells in the cerebral cortex, and EGCG attenuated this decrease. Maintenance of PP2A subunit B is important for normal brain function. CONCLUSION: Therefore, our findings suggest that EGCG exerts neuroprotective effects against cerebral ischemia through modulation of PP2A subunit B expression.

Photo-catalytic and biomedical applications of one-step, plant extract-mediated green-synthesized cobalt oxide nanoparticles.

In the present work, for the first time, green chemically synthesized and stabilized Co3O4 nanoparticles were employed for catalytic conversion of isopropyl alcohol to acetone by dehydrogenation of IPA. Plant extract of Rosmarinus officinalis was used as a reducing and stabilizing agent for this synthesis. The biosynthesized Co3O4 nanoparticles were annealed at 450℃ followed by their physiochemical characterizations through XRD, SEM, AFM, and FTIR. Size distribution information collected through XRD and AFM back each other, and it was found to be 6.5 nm, having the highest number of nanoparticles in this size range. While SEM confirms the self-arranging property of synthesized nanoparticles due to their magnetic nature, furthermore, the biogenic Co3O4 nanoparticles were studied for their catalytic potential to convert isopropyl alcohol to acetone with the help of a UV-Visible spectrophotometer. The highest photocatalytic conversion of 99% was obtained in time period of 48 s. For the first time ever, nanoparticles were used for 5 cycles to evaluate their recyclable nature and conversion fell from 99 to 86% and the end of the 5th cycle. Later anti-bacterial activity against 3 Gram-positive and 3 Gram-negative strains gave the highest inhibition value of 99% against Streptococcus pneumoniae at 500 µg/mL. Finally, a cytotoxicity study on synthesized nanomaterials was carried out by exposing freshly drawn human macrophages to them. It was found that even at the highest concentration of 500 µg/mL, the nanoparticles showed only 28% lysis.

Epigallocatechin gallate restores the reduction of protein phosphatase 2 A subunit B caused by middle cerebral artery occlusion / 한국실험동물학회지

Background@#Epigallocatechin gallate (EGCG) is a flavonoid compound commonly found in green tea. It exhibits antioxidant, anti-inflammatory, and neuroprotective effects in cerebral ischemia. Protein phosphatase 2 A (PP2A) is an important serine/threonine phosphatase enzyme involved in various cellular activities. PP2A subunit B is present abundantly in the brain and plays an important role in the nervous system. We investigated the effect of EGCG on the expression level of PP2A subunit B in cerebral ischemia caused by middle cerebral artery occlusion (MCAO). EGCG (50 mg/kg) or vehicle was injected into the peritoneal cavity prior to MCAO surgery. Neurological behavior tests were performed 24 h after MCAO, and right cerebral cortex tissue was collected. Cerebral ischemia caused serious neurological abnormalities, which were alleviated by EGCG administration. We screened the expression of PP2A subunits containing A, B, and C using reverse-transcription PCR. We confirmed that PP2A subunit B exhibited significant changes in MCAO animals compared to subunits A and C. We continuously examined the expression of PP2A subunit B protein in MCAO animals using Western blot analysis. @*Results@#EGCG alleviated the reduction of PP2A subunit B protein by MCAO damage. In addition, immunohistochemistry demonstrated a decrease in the number of PP2A subunit B-positive cells in the cerebral cortex, and EGCG attenuated this decrease. Maintenance of PP2A subunit B is important for normal brain function. @*Conclusion@#Therefore, our findings suggest that EGCG exerts neuroprotective effects against cerebral ischemia through modulation of PP2A subunit B expression.

Identification of proteins regulated by chlorogenic acid in an ischemic animal model: a proteomic approach / 한국실험동물학회지

Background@#Cerebral ischemia is a serious neurological disorder that can lead to high morbidity and mortality. Chlorogenic acid is a polyphenol compound with antioxidant that can regulate proteins in cerebral ischemia. Middle cerebral artery occlusion (MCAO) surgery was performed to induce ischemic brain injury and was maintained for 24 h. Chlorogenic acid (30 mg/kg) or vehicle was administrated into the peritoneal cavity 2 h after MCAO surgery. The cerebral cortical tissues were collected for further study and a proteomic approach was performed to identify the proteins changed by chlorogenic acid in the MCAO animals. @*Results@#We found that chlorogenic acid alleviated in changes in adenosylhomocysteinase, glycerol-3-phosphate dehydrogenase, eukaryotic translation initiation factor 4A-II, apolipoprotein A-I, and mu-crystallin. These proteins were reduced in MCAO animals with vehicle, and these reductions were attenuated by chlorogenic acid treatment. The mitigation of this reduction by chlorogenic acid was confirmed by the reverse transcription PCR technique. These proteins are associated with energy metabolism, protein synthesis, inflammation, and physiological metabolism. They are involved in the neuroprotective effect of chlorogenic acid. These results showed that chlorogenic acid alleviates the neurological disorders caused by MCAO and regulates the expression of proteins involved in neuroprotection. @*Conclusions@#Therefore, our findings provide evidence that chlorogenic acid plays a neuroprotective role in stroke animal models by controlling specific proteins.

Alleviation of γ-enolase decrease by the chlorogenic acid administration in the stroke animal model

Stroke is a major cause of death and long-term disability. Chlorogenic acid is a phenolic compound with a potent neuroprotective effect. γ-enolase is a phosphopyruvate hydratase found in mature neurons and plays an important role in the neuronal survival. This study investigated whether chlorogenic acid regulates the expression of γ-enolase during cerebral ischemia. Middle cerebral artery occlusion (MCAO) was performed to indcue cerebral ischemia. Adult male rats were used and chlorogenic acid (30 mg/kg) or phosphate buffered saline (PBS) was injected intraperitoneally 2 hours after MCAO surgery. Cerebral cortical tissues were collected 24 hours after MCAO surgery. Our proteomic approach identified the reduction of γ-enolase caused by MCAO damage and the mitigation of this reduction by chlorogenic acid treatment. Results of reverse transcription-polymerase chain reaction and Western blot analyses showed decrease in γ-enolase expression in PBS-treated MCAO group. However, chlorogenic acid treatment attenuated this decrease. Results of immunofluorescence staining showed the change of γ-enolase by chlorogenic acid treatment. These results demonstrated that chlorogenic acid regulates the γ-enolase expression during MCAO-induced ischemia. Therefore, we suggest that chlorogenic acid mediates the neuroprotective function by regulating the γ-enolase expression in cerebral ischemia and may be used as a therapeutic agent for brain diseases including stroke.

Chlorogenic acid modulates the ubiquitin-proteasome system in stroke animal model.

BACKGROUND: Chlorogenic acid, a phenolic compound, has potent antioxidant and neuroprotective properties. The ubiquitin-proteasome system is an important regulators of neurodevelopment and modulators of neuronal function. This system is associated with neurodevelopment and neurotransmission through degradation and removal of damaged proteins. Activation of the ubiquitin-proteasome system is a critical factor in preventing cell death. We have previously reported a decrease in the activity of the ubiquitin-proteasome system during cerebral ischemia. This study investigated whether chlorogenic acid regulates the ubiquitin-proteasome system in an animal stroke model. In adult rats, middle cerebral artery occlusion (MCAO) surgery was performed to induce focal cerebral ischemia. Chlorogenic acid (30 mg/kg) or normal saline was injected into the abdominal cavity 2 h after MCAO surgery, and cerebral cortex tissues were collected 24 h after MCAO damage. RESULTS: Chlorogenic acid attenuated neurobehavioral disorders and histopathological changes caused by MCAO damage. We identified the decreases in ubiquitin C-terminal hydrolase L1, ubiquitin thioesterase OTUB1, proteasome subunit α type 1, proteasome subunit α type 3, and proteasome subunit ß type 4 expression using a proteomics approach in MCAO animals. The decrease in these proteins was alleviated by chlorogenic acid. In addition, the results of reverse transcription-polymerase chain reaction confirmed these changes. The identified proteins were markedly reduced in MCAO damage, while chlorogenic acid prevented these reductions induced by MCAO. The decrease of ubiquitin-proteasome system proteins in ischemic damage was associated with neuronal apoptosis. CONCLUSIONS: Our results showed that chlorogenic acid regulates ubiquitin-proteasome system proteins and protects cortical neurons from neuronal damage. These results provide evidence that chlorogenic acid has neuroprotective effects and maintains the ubiquitin-proteasome system in ischemic brain injury.

Chlorogenic acid alleviates the reduction of Akt and Bad phosphorylation and of phospho-Bad and 14-3-3 binding in an animal model of stroke.

BACKGROUND: Stroke is caused by disruption of blood supply and results in permanent disabilities as well as death. Chlorogenic acid is a phenolic compound found in various fruits and coffee and exerts antioxidant, anti-inflammatory, and anti-apoptotic effects. OBJECTIVES: The purpose of this study was to investigate whether chlorogenic acid regulates the PI3K-Akt-Bad signaling pathway in middle cerebral artery occlusion (MCAO)-induced damage. METHODS: Chlorogenic acid (30 mg/kg) or vehicle was administered peritoneally to adult male rats 2 h after MCAO surgery, and animals were sacrificed 24 h after MCAO surgery. Neurobehavioral tests were performed, and brain tissues were isolated. The cerebral cortex was collected for Western blot and immunoprecipitation analyses. RESULTS: MCAO damage caused severe neurobehavioral disorders and chlorogenic acid improved the neurological disorders. Chlorogenic acid alleviated the MCAO-induced histopathological changes and decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Furthermore, MCAO-induced damage reduced the expression of phospho-PDK1, phospho-Akt, and phospho-Bad, which was alleviated with administration of chlorogenic acid. The interaction between phospho-Bad and 14-3-3 levels was reduced in MCAO animals, which was attenuated by chlorogenic acid treatment. In addition, chlorogenic acid alleviated the increase of cytochrome c and caspase-3 expression caused by MCAO damage. CONCLUSIONS: The results of the present study showed that chlorogenic acid activates phospho-Akt and phospho-Bad and promotes the interaction between phospho-Bad and 14-3-3 during MCAO damage. In conclusion, chlorogenic acid exerts neuroprotective effects by activating the Akt-Bad signaling pathway and maintaining the interaction between phospho-Bad and 14-3-3 in ischemic stroke model.

Knowledge, beliefs, attitude, and practices of E-cigarette use among dental students: A multinational survey.

BACKGROUND: E-cigarette use is a trend worldwide nowadays with mounting evidence on associated morbidities and mortality. Dentists can modify the smoking behaviors of their patients. This study aimed to explore the knowledge, beliefs, attitude, and practice of E-cigarette use among dental students. MATERIALS AND METHODS: This multinational, cross-sectional, questionnaire-based study recruited undergraduate dental students from 20 dental schools in 11 countries. The outcome variable was current smoking status (non-smoker, E-cigarette user only, tobacco cigarette smoker only, dual user). The explanatory variables were country of residence, sex, age, marital status, and educational level. Multiple linear regression analysis was performed to explore the explanatory variables associated with E-cigarette smoking. RESULTS: Of the 5697 study participants, 5156 (90.8%) had heard about E-cigarette, and social media was the most reported source of information for 33.2% of the participants. For the 5676 current users of E-cigarette and/or tobacco smoking, 4.5% use E-cigarette, and 4.6% were dual users. There were significant associations between knowledge and country (P< 0.05), educational level (B = 0.12; 95% CI: 0.02, 0.21; P = 0.016) and smoking status (P< 0.05). The country of residence (P< 0.05) and smoking status (P< 0.05) were the only statistically significant factors associated with current smoking status. Similarly, there were statistically significant associations between attitude and country (P< 0.05 for one country only compared to the reference) and history of previous E-cigarette exposure (B = -0.52; 95% CI: -0.91, -0.13; P = 0.009). Also, the practice of E-cigarettes was significantly associated with country (P< 0.05 for two countries only compared to the reference) and gender (B = -0.33; 95% CI: -0.52, -0.13; P = 0.001). CONCLUSION: The knowledge of dental students about E-cigarette was unsatisfactory, yet their beliefs and attitudes were acceptable. Topics about E-cigarette should be implemented in the dental curriculum.

Retinoic acid regulates the ubiquitin-proteasome system in a middle cerebral artery occlusion animal model.

BACKGROUND: Retinoic acid is a major metabolite of vitamin A and exerts beneficial effects including anti-oxidant and anti-inflammatory activities in neurons. The ubiquitin-proteasome system is an important biological system that regulates cell survival. Ubiquitination regulates protein degradation and plays an important role in oxidative stress. Deubiquitinating enzymes cleave ubiquitin from proteins and control ubiquitination-induced degradation. We detected decreases in ubiquitin carboxy-terminal hydrolase L1, ubiquitin thioesterase OTUB1, and proteasome subunit alpha types 1 and 3 in cerebral ischemic damage. In this study, we investigated whether retinoic acid regulates the expression of deubiquitinating enzymes ubiquitin carboxy-terminal hydrolase L1, ubiquitin thioesterase OTUB1, and proteasome subunit alpha types 1 and 3 in cerebral ischemic injury. Right middle cerebral artery occlusion (MCAO) was performed to induce cerebral ischemic damage in male rats. Retinoic acid (5 mg/kg) or vehicle was intraperitoneally injected every day from 4 days before surgery. Neurological behavioral tests were performed 24 h after MCAO, and right cerebral cortical tissues were collected. RESULTS: MCAO damage caused neurological behavioral dysfunction, and retinoic acid alleviated these deficits. The identified proteins decreased in MCAO animals with vehicle, while retinoic acid treatment attenuated these decreases. The results of proteomic study were confirmed by a reverse transcription-PCR technique. Expressions of ubiquitin carboxy-terminal hydrolase L1, ubiquitin thioesterase OTUB1, and proteasome subunit alpha types 1 and 3 were decreased in MCAO animals treated with vehicle. Retinoic acid treatment alleviated these MCAO-induced reductions. The ubiquitin-proteasome system plays an essential role in maintaining cell function and preserving cell shape against ischemic damage. CONCLUSIONS: These findings suggest that retinoic acid regulates ubiquitin- and proteasome-related proteins including ubiquitin carboxy-terminal hydrolase L1, ubiquitin thioesterase OTUB1, and proteasome subunit alpha types 1 and 3 in a brain ischemia model. Changes in these proteins are involved in the neuroprotective effects of retinoic acid.

Chlorogenic acid alleviates cerebral ischemia-induced neuroinflammation via attenuating nuclear factor kappa B activation.

Ischemic stroke is the most common type of stroke and is caused by vascular closure. Chlorogenic acid is a polyphenolic compound that is present in various plants. It is used as a traditional oriental medicine because of its anti-oxidant and anti-inflammatory properties. We investigated whether chlorogenic acid mediates neuroprotective effects by regulating pro-inflammatory proteins. Focal cerebral ischemia was induced through middle cerebral artery occlusion (MCAO) surgery in adult rats. Chlorogenic acid (30 mg/kg) or vehicle was injected into the abdominal cavity 2 h after MCAO. Rats were sacrificed 24 h after MCAO surgery and brain tissues were isolated immediately. MCAO caused histopathological changes in the ischemic cerebral cortex, and chlorogenic acid attenuated these changes. Chlorogenic acid reduced MCAO-induced reactive oxygen species generation and oxidative stress increase in the cerebral cortex. Furthermore, cerebral ischemia increased the expression of ionized calcium-binding adapter molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP), which are microglia and astrocyte activation markers, respectively. However, chlorogenic acid prevented MCAO-induced these increases. MCAO damage also increased the expression of nuclear factor-κB (NF-κB), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α). Chlorogenic acid treatment attenuated these increases caused by MCAO. These proteins are representative pro-inflammatory markers. This study confirmed that chlorogenic acid exerts an anti-oxidative effect and elucidated anti-inflammatory effect through regulating NF-κB, IL-1ß, and TNF-α on cerebral ischemia. Thus, we can suggest that chlorogenic acid has neuroprotective effects by reducing oxidative stress and controlling pro-inflammatory proteins against cerebral ischemic damage.

Quercetin ameliorates glutamate toxicity-induced neuronal cell death by controlling calcium-binding protein parvalbumin.

BACKGROUND: Glutamate is the main excitatory neurotransmitter. Excessive glutamate causes excitatory toxicity and increases intracellular calcium, leading to neuronal death. Parvalbumin is a calcium-binding protein that regulates calcium homeostasis. Quercetin is a polyphenol found in plant and has neuroprotective effects against neurodegenerative diseases. OBJECTIVES: We investigated whether quercetin regulates apoptosis by modulating parvalbumin expression in glutamate induced neuronal damage. METHODS: Glutamate was treated in hippocampal-derived cell line, and quercetin or vehicle was treated 1 h before glutamate exposure. Cells were collected for experimental procedure 24 h after glutamate treatment and intracellular calcium concentration and parvalbumin expression were examined. Parvalbumin small interfering RNA (siRNA) transfection was performed to detect the relation between parvalbumin and apoptosis. RESULTS: Glutamate reduced cell viability and increased intracellular calcium concentration, while quercetin preserved calcium concentration and neuronal damage. Moreover, glutamate reduced parvalbumin expression and quercetin alleviated this reduction. Glutamate increased caspase-3 expression, and quercetin attenuated this increase in both parvalbumin siRNA transfected and non-transfected cells. The alleviative effect of quercetin was statistically significant in non-transfected cells. Moreover, glutamate decreased bcl-2 and increased bax expressions, while quercetin alleviated these changes. The alleviative effect of quercetin in bcl-2 family protein expression was more remarkable in non-transfected cells. CONCLUSIONS: These results demonstrate that parvalbumin contributes to the maintainace of intracellular calcium concentration and the prevention of apoptosis, and quercetin modulates parvalbumin expression in glutamate-exposed cells. Thus, these findings suggest that quercetin performs neuroprotective function against glutamate toxicity by regulating parvalbumin expression.

Oral health practices and self-reported adverse effects of E-cigarette use among dental students in 11 countries: an online survey.

OBJECTIVES: E-cigarette use has become popular, particularly among the youth. Its use is associated with harmful general and oral health consequences. This survey aimed to assess self-reported oral hygiene practices, oral and general health events, and changes in physiological functions (including physical status, smell, taste, breathing, appetite, etc.) due to E-cigarette use among dental students. METHODS: This online, multicounty survey involved undergraduate dental students from 20 dental schools across 11 different countries. The questionnaire included demographic characteristics, E-cigarette practices, self-reported complaints, and associated physiological changes due to E-cigarette smoking. Data were descriptively presented as frequencies and percentages. A Chi-square test was used to assess the potential associations between the study group and sub-groups with the different factors. Statistical analysis was performed using SPSS at P < 0.05. RESULTS: Most respondents reported regular brushing of their teeth, whereas only 70% used additional oral hygiene aids. Reported frequencies of complaints ranged from as low as 3.3% for tongue inflammation to as high as 53.3% for headache, with significant differences between E-cigarette users and non-users. Compared to non-smokers, E-cigarette users reported significantly higher prevalence of dry mouth (33.1% vs. 23.4%; P < 0.001), black tongue (5.9% vs. 2.8%; P = 0.002), and heart palpitation (26.3%% vs. 22.8%; P = 0.001). Although two-thirds of the sample reported no change in their physiological functions, E-cigarette users reported significant improvement in their physiological functions compared to never smokers or tobacco users. CONCLUSION: Dental students showed good oral hygiene practices, but E-cigarette users showed a higher prevalence of health complications.

Effect of temperature and humidity on coronavirus infection in Pakistan.

Ongoing Coronavirus epidemic (COVID-19) identified first in Wuhan, China posed huge impact on public health and economy around the globe. Both cough and sneeze based droplets or aerosols encapsulated COVID-19 particles are responsible for airborne transmission of this virus and caused an unexpected escalation and high mortality worldwide. Current study intends to investigate the correlation of COVID-19 epidemic with meteorological parameters, particularly temperature and humidity. A data set of Epidemiological data of COVID-19 for highly infected provinces of Pakistan was collected from the official website of (https://www.covid.gov.pk/) and weather data was collected from (https://www.timeanddate.com/) during the time period of 1st March to 30th September 2020. The GrapPad prism 5 Software was used to calculate the mean and standard error of mean (SEM). In the current study the incident of daily covid cases is recorded higher in the month of June while the less number of case were reported in the month of May as compared to the other months (April, May, June, July, September and August) in the four province of Pakistan. We also find out that the incident of Covid19 were high at higher temperature (like the average temperature in the month of June 37 °C) while less cases were reported in May the average temperature was 29.5 °C. Furthermore the incident of covid cases were less reported at low humidity while more intendant with high humidity. Pearson's (r) determine the strength of the relationship between the variables. Pearson's correlation coefficient test employed for data analysis revealed that temperature average (TA) and average humidity is not a significant correlated with COVID-19 pandemic. The results obtained from the current analysis for selected parameters indirect correlation of COVID-19 transmission with temperature variation, and humidity. In the present study association of parameters is not correlated with COVID-19 pandemic, suggested need of more strict actions and control measures for highly populated cities. These findings will be helpful for health regulatory authorities and policy makers to take specific measures to combat COVID-19 epidemic in Pakistan.