Enhanced wheat productivity in saline soil through the combined application of poultry manure and beneficial microbes.

BACKGROUND: Soil salinity is one of the major menaces to food security, particularly in dealing with the food demand of the ever-increasing global population. Production of cereal crops such as wheat is severely affected by soil salinity and improper fertilization. The present study aimed to examine the effect of selected microbes and poultry manure (PM) on seedling emergence, physiology, nutrient uptake, and growth of wheat in saline soil. A pot experiment was carried out in research area of Institute of Soil and Environmental Sciences, University of Agriculture, Faisalabad, Pakistan. Saline soil (12 dS m- 1 w/w) was developed by spiking using sodium chloride, and used in experiment along with two microbial strains (i.e., Alcaligenes faecalis MH-2 and Achromobacter denitrificans MH-6) and PM. Finally, wheat seeds (variety Akbar-2019) were sown in amended and unamended soil, and pots were placed following a completely randomized design. The wheat crop was harvested after 140 days of sowing. RESULTS: The results showed a 10-39% increase (compared to non-saline control) in agronomic, physiological, and nutritive attributes of wheat plants when augmented with PM and microbes. Microbes together with PM significantly enhanced seedling emergence (up to 38%), agronomic (up to 36%), and physiological (up to 33%) in saline soil as compared to their respective unamended control. Moreover, the co-use of microbes and PM also improved soil's physicochemical attributes and enhanced N (i.e., 21.7%-17.1%), P (i.e., 24.1-29.3%), and K (i.e., 28.7%-25.3%) availability to the plant (roots and shoots, respectively). Similarly, the co-use of amendments also lowered the Na+ contents in soil (i.e., up to 62%) as compared to unamended saline control. This is the first study reporting the effects of the co-addition of newly identified salt-tolerant bacterial strains and PM on seedling emergence, physiology, nutrient uptake, and growth of wheat in highly saline soil. CONCLUSION: Our findings suggest that co-using a multi-trait bacterial culture and PM could be an appropriate option for sustainable crop production in salt-affected soil.

Microbes-assisted phytoremediation of lead and petroleum hydrocarbons contaminated water by water hyacinth.

An experiment was carried out to explore the impact of petroleum hydrocarbons (PHs)-degrading microbial consortium (MC) on phytoremediation ability and growth of water hyacinth (WH) plants in water contaminated with lead (Pb) and PHs. Buckets (12-L capacity) were filled with water and WH plants, PHs (2,400 mg L-1) and Pb (10 mg L-1) in respective buckets. Plants were harvested after 30 days of transplanting and results showed that PHs and Pb substantially reduced the agronomic (up to 62%) and physiological (up to 49%) attributes of WH plants. However, the application of MC resulted in a substantial increase in growth (38%) and physiology (22%) of WH plants over uninoculated contaminated control. The WH + MC were able to accumulate 93% Pb and degrade/accumulate 72% of PHs as compared to initial concentration. Furthermore, combined use of WH plants and MC in co-contamination of PHs and Pb, reduced Pb and PHs contents in water by 74% and 68%, respectively, than that of initially applied concentration. Our findings suggest that the WH in combination with PHs-degrading MC could be a suitable nature-based water remediation technology for organic and inorganic contaminants and in future it can be used for decontamination of mix pollutants from water bodies.

Phytoremediation by aquatic macrophytes is a promising technique for the cleanup of environmental toxins from wastewater. To our knowledge, this is the first study reporting the integrated use of water hyacinth (WH) plants and a newly developed multi-trait microbial consortium for the simultaneous remediation of organic (i.e., petroleum hydrocarbons) and inorganic (i.e., lead) pollutants from the contaminated water. Findings of this study provide the basic but important information on the combined use of WH and microbes for remediation of mix pollution from water bodies.

Genetic causes of inherited retinal diseases among Israeli Jews of Ethiopian ancestry.

Purpose: This study sought to describe the phenotype frequency and genetic basis of inherited retinal diseases (IRDs) among a nationwide cohort of Israeli Jewish patients of Ethiopian ancestry. Methods: Patients' data-including demographic, clinical, and genetic information-were obtained through members of the Israeli Inherited Retinal Disease Consortium (IIRDC). Genetic analysis was performed by either Sanger sequencing for founder mutations or next-generation sequencing (targeted next-generation sequencing or whole-exome sequencing). Results: Forty-two patients (58% female) from 36 families were included, and their ages ranged from one year to 82 years. Their most common phenotypes were Stargardt disease (36%) and nonsyndromic retinitis pigmentosa (33%), while their most common mode of inheritance was autosomal recessive inheritance. Genetic diagnoses were ascertained for 72% of genetically analyzed patients. The most frequent gene involved was ABCA4. Overall, 16 distinct IRD mutations were identified, nine of which are novel. One of them, ABCA4-c.6077delT, is likely a founder mutation among the studied population. Conclusions: This study is the first to describe IRDs' phenotypic and molecular characteristics in the Ethiopian Jewish community. Most of the identified variants are rare. Our findings can help caregivers with clinical and molecular diagnosis and, we hope, enable adequate therapy in the near future.

Molecular mechanisms of morphine tolerance and dependence; novel insights and future perspectives.

Drug addiction is a devastating condition that poses a serious burden on the society. The use of some drugs like morphine for their tremendous analgesic properties is also accompanied with developing tolerance, dependence and the withdrawal symptoms. These symptoms are frequently severe enough to reinforce the person in recovery to start over the use of drug again and hinder the clinical use of drugs like morphine for chronic pain. Research into opioid receptors and related molecular pathways has seen resurgence in the wake of the growing opioid epidemic. The current study provides a comprehensive scientific exploration of the molecular mechanisms and underlying signalling in morphine tolerance and dependence. It also critically evaluates current therapeutic approaches, shedding light on their efficacy and limitations, and future prospects. The graphical abstract depicts an overview of the pathways involved in the emergence of morphine-related tolerance and dependence including NMDA, Nitric oxide, and PPAR, as well as behavioural sensitization along with present and future innovative treatment strategies including stem cell therapy that have been discussed in the current manuscript.

An eco-friendly approach on green synthesis, bio-engineering applications, and future outlook of ZnO nanomaterial: A critical review.

Synthesizing ZnO nanostructures ranging from 1 nm to 4 nm confines the electron cloud and exhibits a quantum effect generally called as quantum confinement effect attracting many researchers in the field of electronics and optics. ZnO nanostructures are used in medical applications to formulate antioxidant, antibacterial, antifungal, anti-inflammatory, wound healing, and anti-diabetic medications. This work is a comprehensive study of green synthesis of ZnO nanomaterials using different biological sources and highlights different processes able to produce nanostructures including nanowires, nanorods, nanotubes and other nano shapes of ZnO nanostructures. Different properties of ZnO nanostructures and their targeted bioengineering applications are also described. The strategies and challenges of the eco-friendly approach to enhance the application span of ZnO nanomaterials are also summarized, with future prospects for greener design of ZnO nanomaterials are also suggested.

Design of tropinium-functionalized anion exchange membranes for acid recovery via diffusion dialysis process.

Diffusion dialysis (DD) process utilizing anion exchange membranes (AEMs) is an environmentally-friendly and energy-efficient technology. From acidic wastewater, DD is needed for acid recovery. This research reports the development of a series of dense tropinium-functionalized AEMs via solution casting method. Fourier Infrared transform (FTIR) spectroscopy verified the successful preparation of AEMs. The developed AEMs exhibited a dense morphology, featuring 0.98-2.42 mmol/g of ion exchange capacity (IEC), 30-81% of water uptake (WR) and 7-32% of linear swelling ratio (LSR). They displayed exceptional mechanical, thermal and chemical stability and were employed for acid waste treatment from HCl/FeCl2 mixtures via DD process. AEMs possessed 20 to 59 (10-3 m/h) and 166 to 362 of acid diffusion dialysis coefficient (UH+) and separation factor (S) respectively at 25 °C. Compared to DF-120 commercial membrane (UH+ = 0.004 m/h, S = 24.3), their DD efficiency was improved under identical experimental conditions.

Investigation on synthesis of ternary g-C3N4/ZnO-W/M nanocomposites integrated heterojunction II as efficient photocatalyst for environmental applications.

The rapid industrialization of the world is disparagingly manipulating our environment and natural ecosystem. The researchers are taking keen interest to invent novel material as photocatalyst for non-degradable organic pollutants. Solar energy-driven practices employing semiconductors are a novel approach towards wastewater remediation. Here in, we successfully synthesized a vigorous photocatalysts comprising of g-C3N4 and doped ZnO-W/M (M = Co, Ce, Yb, Sm) by co-precipitation followed by metals doping via calcination approach. The structural, morphological, and photocatalytic applications for organic pollutants of synthesized heterostructure nanocomposites were examined by XRD, FTIR, SEM, EDX and UV visible spectrophotometer. Diffraction peaks attributed to both g-C3N4 and ZnO-W were detected in the XRD spectra. The FTIR spectra also inveterate the formation of g-C3N4/ZnO-W/M composites. The SEM images reveal an agglomerated morphology and EDS analysis also confirmed close contact between g-C3N4, ZnO-W and doped metals. The abridged energy band gap of g-C3N4/ZnO-W/M (M = Ce, Yb, Sm, Co) nanocomposites calculated via Tauc plot are 2.68, 2.88, 3.24 and 3.29 eV respectively. Narrowing of bandgap is considered an imperative triumph for the degradation of industrial effluents. The photocatalytic activity was performed against four different dyes and follows the trend Ce > Yb > Sm > Co. The recyclability tests were carried out for different dyes and no substantial catalytic activity loss was observed even after the fourth experimental run, which proves that reported ternary heterojunctions exhibit high mechanical stability and reusability.The species trapping experiment exposed that generated h+ are the principal active specie for dye photodegradation reactions. This work disseminates a novel photocatalyst for the removal of synthetic dyes.

Correction: Khan et al. Therapeutic Effects of Saponins for the Prevention and Treatment of Cancer by Ameliorating Inflammation and Angiogenesis and Inducing Antioxidant and Apoptotic Effects in Human Cells. Int. J. Mol. Sci. 2022, 23, 10665.

In the original publication by Khan et al [...].

Pterostilbene reduces the progression of atopic dermatitis via modulating inflammatory and oxidative stress biomarkers in mice.

Atopic dermatitis (AD) is one of the most prevalent chronic skin inflammatory disorders requiring continuous treatment and care. Pterostilbene (PTN) belongs to stilbene and is a polyphenolic compound of natural origin. It is similar to resveratrol and has analogous anti-inflammatory, anti-oxidant, and anti-carcinogenic characteristics. This study was intended to evaluate the effect of PTN against atopic dermatitis. The disease was induced by sensitization with 2,4-dinitrochlorobenzene (DNCB) in mice. The standard control group (SCG) received topical 0.1% tacrolimus (TC), whereas three other treatment groups received daily topical PTN at 0.2, 0.6, and 1% w/w for 28 days. Dermatitis scoring, ear thickness, and body weight of animals were weekly determined while other parameters were assessed at the termination of the experiment. PTN reduced the ear weight, skin thickness, and the weight and size of thymus glands and spleen in comparison with diseased animals. PTN also reduced the elevated immunoglobulin E (IgE) level and blood inflammatory cells in diseased mice. The histopathological findings showed a decreased epidermal thickness in PTN-treated groups. Moreover, treatment with PTN improved the amount of oxidative stress markers in the skin of the diseased mice. The expressions of IL-4, IL-6, TNF-α, and NF-κB in the skin of diseased mice were also reduced by PTN. This study concludes that PTN ameliorated the symptoms of atopic dermatitis through the reduction of inflammation, oxidative damage, and inflammatory cytokines in the skin of diseased animals. Therefore, PTN must be further investigated for the treatment of AD complications and other inflammatory skin disorders.

Establishment of institutional diagnostic reference level for Computed Tomography dose on 160 slicer Computed Tomography scan at Lady Reading Hospital Peshawar.

OBJECTIVE: To set institutional diagnostic reference level for computed tomography of multiple anatomical regions using dose length product as dosimeter parameter and to compare results with international diagnostic reference level. Method: The retrospective study was conducted at the Radiology Unit of Lady Reading Hospital, Peshawar, Pakistan, and comprised dose data of patients who underwent computed tomography from June 1 to August 31, 2018. The mean, 25th, 50th and 75th percentile of dose distribution of common computed tomography examinations was calculated and compared with other established diagnostic reference levels. Data was analysed using SPSS 20. RESULTS: Of the 1001 scans, 143(14.2%) related to brain, 275(27.5%) abdomen-pelvis, 133(13.3%) kidney-ureter-bladder, 186(18.58%) thorax, 85(8.49%) triphasic, 126(12.58%) musculoskeletal, and 53(5.29%) cardiac. Institutional diagnostic reference levels for the computed tomography unit was established as 50th percentile of dose length product for different regions brain 339, abdomen-pelvis 298, thorax 165, kidney-ureter-bladder 302, triphasic 633, musculoskeletal 366 and cardiac 403. Both 50th and 75th percentile values of dose length product for each individual body region was lower than international Diagnostic reference levels. CONCLUSIONS: The diagnostic reference level will be used in routine computed tomography practice at the institution, and will act as the baseline for developing the national diagnostic reference levels.

The mystery of post-cholecystectomy persistent bile leak: a case report.

Laparoscopic cholecystectomy (LC) is commonly performed for benign gallbladder diseases. Biliary leak is the most common complication of bile duct injury following this surgery. We report a case of persistent bile leak following the procedure despite endoscopic and radiological management. A female patient presented to the hepatopancreatobiliary unit of the Bahria International Hospital (Orchard), Lahore, with complaint of persistent bile leakage after laparoscopic cholecystectomy performed elsewhere. She had been investigated in various hospitals but the cause of the persistent bile leak remained a mystery and she was offered surgery. After real time fluoroscopic contrast enhanced imaging, further confirmed by a Computerised Tomography (CT) Scan of the abdomen, it was revealed that the persistent bile leak in the drain was due to iatrogenic injury of the duodenum secondary to percutaneous catheter insertion. The patient was managed non-surgically. She remained stable. This is a rare complication of one of the most common surgical procedures performed in the world.

Genetic diversity and forensic application of Y-filer STRs in four major ethnic groups of Pakistan.

17 Y-chromosomal STRs which are part of the Yfiler Amplification Kit were investigated in 493 unrelated Pakistani individuals belonging to the Punjabi, Sindhi, Baloch, and Pathan ethnic groups. We have assessed the forensic parameters and population genetic structure for each group. Among the 493 unrelated individuals from four ethnic groups (128 Baloch, 122 Pathan, 108 Punjabi, and 135 Sindhi), 82 haplotypes were observed with haplotype diversity (HD) of 0.9906 in Baloch, 102 haplotypes with HD value of 0.9957 in Pathans, 80 haplotypes with HD value of 0.9924 in Punjabi, and 105 haplotypes with HD value of 0.9945 in the Sindhi population. The overall gene diversity for Baloch, Pathan, Punjabi, and Sindhi populations was 0.6367, 0.6479, 0.6657, and 0.6112, respectively. The results had shown us that Pakistani populations do not have a unique set of genes but share the genetic affinity with regional (Central Asia and Northern India) populations. The observed low gene diversity (heterozygosity) values may be because of endogamy trends and this observation is equally supported by the results of forensic parameters which are mostly static across 4 combinations (minimal STRs, extended 11 Y-STRs, Powerplex 12 Y System, and Yfiler 17 Y-STRs) of STRs in these four populations.

Role of gene regulation and inter species interaction as a key factor in gut microbiota adaptation.

Gut microbiota is a class of microbial flora present in various eukaryotic multicellular complex animals such as human beings. Their community's growth and survival are greatly influenced by various factors such as host-pathogen, pathogen-environment and genetic regulation. Modern technologies like metagenomics have particularly extended our capacity to uncover the microbial treasures in challenging conditions like communities surviving at high altitude. Molecular characterizations by newly developed sequencing tools have shown that this complex interaction greatly influences microbial adaptation to the environment. Literature shows that gut microbiota alters the genetic expression and switches to an alternative pathway under the influence of unfavorable conditions. The remarkable adaptability of microbial genetic regulatory networks enables them to survive and expand in tough and energy-limited conditions. Variable prevalence of species in various regions has strengthened this initial evidence. In view of the interconnection of the world in the form of a global village, this phenomenon must be explored more clearly. In this regard, recently there has been significant addition of knowledge to the field of microbial adaptation. This review summarizes and shed some light on mechanisms of microbial adaptation via gene regulation and species interaction in gut microbiota.

Mechanisms of gene regulation by histone degradation in adaptation of yeast: an overview of recent advances.

Histones are important component of eukaryotic cells chromatin and consist of arginine and lysine residues. Histones play an important role in the protection of DNA. Their contents significantly affect high-level chromatin structure formation, gene expression, DNA replication, and other important life activities. Protein degradation is an important regulatory mechanism of histone content. Recent studies have revealed that modification of amino acid sequence is directly related to histone breakdown. In addition, histone degradation is closely related to covalent modifications, such as ubiquitination and acetylation, which are considered to be driving factors in gene regulation. Gene regulation is an important mechanism in adaptation to the environment and survival of species. With the introduction of highly efficient technology, various mutations in histones have been identified in yeast. In the field of epigenetics and the transmission of chromatin states, two widely used model organisms are the budding yeast Saccharomyces cerevisiae and Schizosaccharomyces pombe. Higher eukaryotes can use their silent loci to maintain their epigenetic states and providing the base to investigate mechanisms underlying development. Therfore, both species have contributed a plethora of information on these mechanisms in both yeast and higher eukaryotes. This study focuses on the role of histone modifications in controlling telomeric silencing in Saccharomyces cerevisiae and centromeric silencing in S. pombe as examples of genetic loci that demonstrate epigenetic inheritance. In view of recent advances, this review focuses on the post-translational modification of histone amino acid residues and reviews the relationship between histone degradation and amino acid residue modification.

Gums-based engineered bio-nanostructures for greening the 21st-century biotechnological settings.

Naturally occurring plant-based gums and their engineered bio-nanostructures have gained an immense essence of excellence in several industrial, biotechnological, and biomedical sectors of the modern world. Gums derived from bio-renewable resources that follow green chemistry principles are considered green macromolecules with unique structural and functional attributes. For instance, gum mostly obtained as exudates are bio-renewable, bio-degradable, bio-compatible, sustainable, overall cost-effective, and nontoxic. Gum exudates also offer tunable attributes that play a crucial role in engineering bio-nanostructures of interest for several bio- and non-bio applications, e.g., food-related items, therapeutic molecules, sustained and controlled delivery cues, bio-sensing constructs, and so on. With particular reference to plant gum exudates, this review focuses on applied perspectives of various gums, i.e., gum Arabic, gum albizzia, gum karaya, gum tragacanth, and gum kondagogu. After a brief introduction with problem statement and opportunities, structural and physicochemical attributes of plant-based natural gums are presented. Following that, considerable stress is given to green synthesis and stabilization of gum-based bio-nanostructures. The final part of the review focuses on the bio- and non-bio related applications of various types of gums polysaccharides-oriented bio-nanostructures.

Endocrine disruption: Reproductive toxicity of glyceryl trinitrate and isosorbide mononitrate in male Wistar rats.

Glyceryl trinitrate (GTN) and isosorbide mononitrate (IM) are organic nitrates which release nitric oxide upon metabolism with potential to adversely affect male reproductive function. Therefore, this study was designed to evaluate the sub-chronic effect of these organic nitrates on reproductive system in male rats. Wistar rats were separately treated with GTN and IM at 2.5, 5 and 7.5 mg/kg/day by oral gavage for 45 days. At the end of treatment, serum blood samples were taken from anaesthetized rats for assessment of hormonal profile. Epididymis was removed to analyse sperm parameters. Rat testes were dissected to perform histopathological evaluation and oxidative stress biomarkers. The GTN and IM treated groups showed a significant decrease in sperm parameters (count, motility and viability) and serum testosterone in comparison to normal control group. The GTN and IM treatment also altered sperm morphology such as bent tail and head deformities as compared to control. A significant decrease in catalase activity and, increase in nitric oxide and malondialdehyde were observed in high dose drug treated groups. Moreover, a significant increase in follicle stimulating hormone and decrease in testosterone levels were evident in all drug treated groups. The level of luteinizing hormone was raised in rats treated with medium doses of drugs while it decreased at the highest dose of both drugs. Histological study showed vacuolization and degeneration of seminiferous tubules. It is concluded that GTN and IM treatment adversely affected the male reproductive function by altering sperm parameters and disrupting the reproductive hormone profile which may be attributed to the increased level of nitric oxide and oxidative stress.

Comparing Analgesia on an As-Needed Basis to Traditional Intravenous Patient-Controlled Analgesia Within Fast-Track Orthopedic Procedures: A Randomized Controlled Trial.

BACKGROUND: The aim was to determine if the use of intravenous patient-controlled analgesia (IVPCA) in a fast-track joint replacement program is associated with increased use of perioperative opioid consumption and increased length of hospital stay. DESIGN: A prospective, double-blind, randomized controlled trial. SETTINGS: Academic hospital. PARTICIPANTS/SUBJECTS: A total of 80 patients aged 18-85 years, with body mass index (BMI) 18-40, undergoing elective total knee arthroplasty were recruited. METHODS: Pre-operatively, patients received gabapentin, celecoxib, and acetaminophen. Peri-operatively, patients received spinal anesthesia with morphine and fentanyl, and periarticular local anesthetic administration by the surgeon. Postoperatively, 80 patients were randomized by a computer-generated sequence into IVPCA group (group A, n = 40) and non-IVPCA group (group B, n = 40). RESULTS: The primary outcome was 48-hour postoperative opioid consumption and length of hospital stay. Secondary outcomes included side effects of opioids, patient satisfaction, and pain scores. There was no significant difference within 48-hour postoperative opioid consumption (median 61.3 vs. 87.5, p = .181) and length of hospital stay (median 49.8 hours vs. 49.5 hours; p = .89) between the two groups. Also, there was no significant difference in patient satisfaction (median 5 in both groups), pain scores, and opioid-related side effects. CONCLUSIONS: IVPCA was associated with nonsignificant reduction in opioid exposure in elective total knee arthroplasty surgery within 48 hours. Neither group was superior in terms of length of hospital stay, opioid related side-effects, pain scores, and patient satisfaction.

Therapeutic Effects of Saponins for the Prevention and Treatment of Cancer by Ameliorating Inflammation and Angiogenesis and Inducing Antioxidant and Apoptotic Effects in Human Cells.

Saponins are natural compounds found in plants and have a diverse range of applications. However, the therapeutic potential of saponins in regulating cytotoxicity, angiogenesis, and inflammation in mammalian cells is yet to be explored. Here, we investigated the therapeutic effects of saponins from green tea by exploring the cytotoxic effects of saponins by inducing apoptosis in the human cancer cell lines hepatocellular carcinoma (HEPG2) and colorectal adenocarcinoma (HT29). The anti-angiogenesis effect of saponins was also investigated in human umbilical vein endothelial cells (HUVEC). We explored the ability of saponins to attenuate inflammation in a dose-dependent manner in normal human cells. It was found that saponins exhibit cytotoxic effects in cancer cells and not in normal cells at the same concentration. Cytotoxicity was measured by inducing apoptosis by enhancing caspase-3 (cas-3) activation and B-cell lymphoma-2 (Bcl-2)-associated X protein (BAX) gene expression and suppressing the antiapoptotic protein, Bcl-2. The inhibition of HUVEC proliferation was due to the suppression of the phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), vascular endothelial growth factor receptor-2 (VEGFR-2), and nuclear factor kappa B (NF-κB). We also observed the antioxidant potential of green tea-derived saponins against free radicals in reactive oxygen species (ROS)-induced cells. Here we observed that the saponins exhibited free radical scavenging activities and activated nuclear factorerythroid 2-related factor 2 (NRF-2) leading to the upregulation of antioxidant-related genes in human embryonic kidney 293 (HEK293) cells. Furthermore, we demonstrated that the anti-inflammatory effects were due to the suppression of pro-inflammatory cytokines interleukin (IL)-1ß, IL-6, tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in HEK293 cells. The significance of the work is we are the first to report on the anti-cancer effects of saponins based on the anti-inflammatory, antioxidant, anti-angiogenesis, and apoptosis induction properties. In conclusion, green tea-derived saponins could be effective therapeutics for the treatment of cancer.

Neuroprotective Effects of Green Tea Seed Isolated Saponin Due to the Amelioration of Tauopathy and Alleviation of Neuroinflammation: A Therapeutic Approach to Alzheimer's Disease.

Tauopathy is one of the major causes of neurodegenerative disorders and diseases such as Alzheimer's disease (AD). Hyperphosphorylation of tau proteins by various kinases leads to the formation of PHF and NFT and eventually results in tauopathy and AD; similarly, neuroinflammation also exaggerates and accelerates neuropathy and neurodegeneration. Natural products with anti-tauopathy and anti-neuroinflammatory effects are highly recommended as safe and feasible ways of preventing and /or treating neurodegenerative diseases, including AD. In the present study, we isolated theasaponin E1 from ethanol extract of green tea seed and evaluated its therapeutic inhibitory effects on tau hyper-phosphorylation and neuroinflammation in neuroblastoma (SHY-5Y) and glioblastoma (HTB2) cells, respectively, to elucidate the mechanism of the inhibitory effects. The expression of tau-generating and phosphorylation-promoting genes under the effects of theasaponin E1 were determined and assessed by RT- PCR, ELISA, and western blotting. It was found that theasaponin E1 reduced hyperphosphorylation of tau and Aß concentrations significantly, and dose-dependently, by suppressing the expression of GSK3 ß, CDK5, CAMII, MAPK, EPOE4(E4), and PICALM, and enhanced the expression of PP1, PP2A, and TREM2. According to the ELISA and western blotting results, the levels of APP, Aß, and p-tau were reduced by treatment with theasaponin E1. Moreover, theasaponin E1 reduced inflammation by suppressing the Nf-kB pathway and dose-dependently reducing the levels of inflammatory cytokines such as IL-1beta, IL-6, and TNF-alpha etc.

Pterostilbene improves CFA-induced arthritis and peripheral neuropathy through modulation of oxidative stress, inflammatory cytokines and neurotransmitters in Wistar rats.

Pterostilbene is a stilbene flavonoid that occurs naturally in various plants as well as produced by genetic engineering. It exhibits anti-inflammatory, analgesic, anti-oxidant and neuroprotective activities. This research was aimed to determine the potential of pterostilbene against arthritis and peripheral neuropathy in Complete Freund's Adjuvant (CFA) induced arthritis. Rat hind paw was injected with 0.1 ml CFA to induce arthritis. Standard control animals received oral methotrexate (3 mg/kg/week). Pterostilbene at 12.5, 25 and 50 mg/kg was given orally to different groups of arthritic rats from day 7-28 for 21 days. Pterostilbene significantly reduced paw diameter and retarded the decrease in body weight of arthritic rats. It profoundly (p < 0.05-0.0001) reduced lipid peroxidation and nitrites, while increased superoxide dismutase (SOD) in the liver tissue. Pterostilbene treatment significantly (p < 0.0001) reduced TNF-α and IL-6 levels. Pterostilbene markedly improved (p < 0.05-0.001) motor activity and showed analgesic effect in arthritic rats at 25 and 50 mg/kg as compared to disease control rats. Furthermore, it notably (p < 0.05-0.0001) increased SOD activity, nitrites, noradrenaline and serotonin levels in the sciatic nerve of arthritic rats. Treatment with pterostilbene also ameliorated the CFA-induced pannus formation, cartilage damage and synovial hyperplasia in the arthritic rat paws. It is determined from the current study that pterostilbene was effective in reducing CFA-induced arthritis in rats through amelioration of oxidative stress and inflammatory mediators. It was also effective to treat peripheral neuropathy through modulation of oxidative stress and neurotransmitters in sciatic nerves.