Multi-transcriptomics reveals brain cellular responses to peripheral infection in Alzheimer's disease model mice.

Peripheral inflammation has been linked to various neurodegenerative disorders, including Alzheimer's disease (AD). Here we perform bulk, single-cell, and spatial transcriptomics in APP/PS1 mice intranasally exposed to Staphylococcus aureus to determine how low-grade peripheral infection affects brain transcriptomics and AD-like pathology. Chronic exposure led to increased amyloid plaque burden and plaque-associated microglia, significantly affecting the transcription of brain barrier-associated cells, which resulted in barrier leakage. We reveal cell-type- and spatial-specific transcriptional changes related to brain barrier function and neuroinflammation during the acute infection. Both acute and chronic exposure led to brain macrophage-associated responses and detrimental effects in neuronal transcriptomics. Finally, we identify unique transcriptional responses at the amyloid plaque niches following acute infection characterized by higher disease-associated microglia gene expression and a larger effect on astrocytic or macrophage-associated genes, which could facilitate amyloid and related pathologies. Our findings provide important insights into the mechanisms linking peripheral inflammation to AD pathology.

Potential Therapeutic Approach of Melatonin against Omicron and Some Other Variants of SARS-CoV-2.

The Omicron variant (B.529) of COVID-19 caused disease outbreaks worldwide because of its contagious and diverse mutations. To reduce these outbreaks, therapeutic drugs and adjuvant vaccines have been applied for the treatment of the disease. However, these drugs have not shown high efficacy in reducing COVID-19 severity, and even antiviral drugs have not shown to be effective. Researchers thus continue to search for an effective adjuvant therapy with a combination of drugs or vaccines to treat COVID-19 disease. We were motivated to consider melatonin as a defensive agent against SARS-CoV-2 because of its various unique properties. Over 200 scientific publications have shown the significant effects of melatonin in treating diseases, with strong antioxidant, anti-inflammatory, and immunomodulatory effects. Melatonin has a high safety profile, but it needs further clinical trials and experiments for use as a therapeutic agent against the Omicron variant of COVID-19. It might immediately be able to prevent the development of severe symptoms caused by the coronavirus and can reduce the severity of the infection by improving immunity.

Autophagy Modulation in Aggresome Formation: Emerging Implications and Treatments of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most prevailing neurodegenerative diseases in the world, which is characterized by memory dysfunction and the formation of tau and amyloid ß (Aß) aggregates in multiple brain regions, including the hippocampus and cortex. The formation of senile plaques involving tau hyperphosphorylation, fibrillar Aß, and neurofibrillary tangles (NFTs) is used as a pathological marker of AD and eventually produces aggregation or misfolded protein. Importantly, it has been found that the failure to degrade these aggregate-prone proteins leads to pathological consequences, such as synaptic impairment, cytotoxicity, neuronal atrophy, and memory deficits associated with AD. Recently, increasing evidence has suggested that the autophagy pathway plays a role as a central cellular protection system to prevent the toxicity induced by aggregation or misfolded proteins. Moreover, it has also been revealed that AD-related protein aggresomes could be selectively degraded by autophagosome and lysosomal fusion through the autophagy pathway, which is known as aggrephagy. Therefore, the regulation of autophagy serve as a useful approach to modulate the formation of aggresomes associated with AD. This review focuses on the recent improvements in the application of natural compounds and small molecules as a potential therapeutic approach for AD prevention and treatment via aggrephagy.

Serial Passaging of RAW 264.7 Cells Modulates Intracellular AGE Formation and Downregulates RANKL-Induced In Vitro Osteoclastogenesis.

The passage number of cells refers to the number of subculturing processes that the cells have undergone. The effect of passage number on morphological and phenotypical characteristics of cells is of great importance. Advanced glycation end products have also been associated with cell functionality and characteristics. Murine monocyte RAW 264.7 cells differentiate into osteoclasts upon receptor activation caused by nuclear factor-kappa-Β ligand (RANKL) treatment. This study aims to identify the role of passage number on intracellular advanced glycation end products (AGEs) formation and osteoclastogenic differentiation of RAW 264.7 cells. Western blotting was performed to check intracellular AGE formation along with fluorometric analysis using a microplate reader. Tartrate-resistant acid phosphatase (TRAP) staining was performed to check osteoclastogenic differentiation, and qPCR was realized to check the responsible mRNA expression. Immunofluorescence was used to check the morphological changes. Intracellular AGE formation was increased with passaging, and the higher passage number inhibited multinucleated osteoclastogenic differentiation. Osteoclastogenic gene expression also showed a reducing trend in higher passages, along with a significant reduction in F-actin ring size and number. Lower passages should be used to avoid the effects of cell subculturing in in vitro osteoclastogenesis study using RAW 264.7 cells.

Antioxidant and Signal-Modulating Effects of Brown Seaweed-Derived Compounds against Oxidative Stress-Associated Pathology.

The biological and therapeutic properties of seaweeds have already been well known. Several studies showed that among the various natural marine sources of antioxidants, seaweeds have become a potential source of antioxidants because of their bioactive compounds. Most of the metabolic diseases are caused by oxidative stress. It is very well known that antioxidants have a pivotal role in the treatment of those diseases. Recent researches have revealed the potential activity of seaweeds as complementary medicine, which have therapeutic properties for health and disease management. Among the seaweeds, brown seaweeds (Phaeophyta) and their derived bioactive substances showed excellent antioxidant properties than other seaweeds. This review focuses on brown seaweeds and their derived major bioactive compounds such as sulfated polysaccharide, polyphenol, carotenoid, and sterol antioxidant effects and molecular mechanisms in the case of the oxidative stress-originated disease. Antioxidants have a potential role in the modification of stress-induced signaling pathways along with the activation of the oxidative defensive pathways. This review would help to provide the basis for further studies to researchers on the potential antioxidant role in the field of medical health care and future drug development.

Infrequent Pattern Detection for Reliable Network Traffic Analysis Using Robust Evolutionary Computation.

While anomaly detection is very important in many domains, such as in cybersecurity, there are many rare anomalies or infrequent patterns in cybersecurity datasets. Detection of infrequent patterns is computationally expensive. Cybersecurity datasets consist of many features, mostly irrelevant, resulting in lower classification performance by machine learning algorithms. Hence, a feature selection (FS) approach, i.e., selecting relevant features only, is an essential preprocessing step in cybersecurity data analysis. Despite many FS approaches proposed in the literature, cooperative co-evolution (CC)-based FS approaches can be more suitable for cybersecurity data preprocessing considering the Big Data scenario. Accordingly, in this paper, we have applied our previously proposed CC-based FS with random feature grouping (CCFSRFG) to a benchmark cybersecurity dataset as the preprocessing step. The dataset with original features and the dataset with a reduced number of features were used for infrequent pattern detection. Experimental analysis was performed and evaluated using 10 unsupervised anomaly detection techniques. Therefore, the proposed infrequent pattern detection is termed Unsupervised Infrequent Pattern Detection (UIPD). Then, we compared the experimental results with and without FS in terms of true positive rate (TPR). Experimental analysis indicates that the highest rate of TPR improvement was by cluster-based local outlier factor (CBLOF) of the backdoor infrequent pattern detection, and it was 385.91% when using FS. Furthermore, the highest overall infrequent pattern detection TPR was improved by 61.47% for all infrequent patterns using clustering-based multivariate Gaussian outlier score (CMGOS) with FS.

Inhibitory Effects of Astaxanthin on CML-HSA-Induced Inflammatory and RANKL-Induced Osteoclastogenic Gene Expression in RAW 264.7 Cells.

OBJECTIVE: Elevated levels of serum Nε-carboxymethyllysine (CML), a well-known advanced glycation end-product (AGE), were observed in patients with inflammation or osteoporosis. Astaxanthin was reported to possess anti-inflammatory and antioxidant effects. In the present study, we investigated the effects of commercially available dietary supplement AstaReal ACTR (ASR) capsule content as astaxanthin on CML-HSA-induced inflammatory and receptor activator of nuclear factor-kappa-Β ligand (RANKL)-induced osteoclastogenic gene expression. METHODS: RAW 264.7 murine macrophage cells were stimulated with CML-HSA to trigger inflammatory gene expression and treated with either a vehicle control or varied concentrations of astaxanthin. Inflammatory gene expression was measured using an enzyme-linked immunosorbent assay (ELISA) or qPCR. We triggered osteoclastogenesis using RANKL, and osteoclastogenic gene expression was measured through tartrate-resistant acid phosphatase (TRAP) activity, staining, immunofluorescence, and qPCR analyses. RESULTS: CML-HSA showed a stimulatory effect on inflammatory gene expression, and astaxanthin reduced the expression by at least two-fold. The levels of autoinflammatory gene expression were reduced by astaxanthin. The RANKL-induced osteoclastogenesis was significantly inhibited by astaxanthin, with reductions in the activation of nuclear factor-κB (NF-κB), the expression of NFATc1 (nuclear factor of activated T cells 1), multinucleated cell formation, and the expression of mature osteoclast marker genes. CONCLUSION: Astaxanthin has potential as a remedy for CML-HSA-induced inflammation and RANKL-induced excessive bone loss.

Emerging risk of environmental factors: insight mechanisms of Alzheimer's diseases.

Neurodegenerative disorders are typically sporadic in nature in addition to usually influenced through an extensive range of environmental factors, lifestyle, and genetic elements. Latest observations have hypothesized that exposure of environmental factors may increase the prospective risk of Alzheimer's diseases (AD). However, the role of environmental factors as a possible dangerous issue has extended importance concerned in AD pathology, although actual etiology of the disorder is still not yet clear. Thus, the aim of this review is to highlight the possible correlation between environmental factors and AD, based on the present literature view. Environmental risk factors might play an important role in decelerating or accelerating AD progression. Among well-known environmental risk factors, prolonged exposure to several heavy metals, for example, aluminum, arsenic, cadmium, lead, and mercury; particulate air, and some pesticides as well as metal-containing nanoparticles have been participated to cause AD. These heavy metals have the capacity to enhance amyloid ß (Aß) peptide along with tau phosphorylation, initiating amyloid/senile plaques, as well as neurofibrillary tangle formation; therefore, neuronal cell death has been observed. Furthermore, particulate air, pesticides, and heavy metal exposure have been recommended to lead AD susceptibility and phenotypic diversity though epigenetic mechanisms. Therefore, this review deliberates recent findings detailing the mechanisms for a better understanding the relationship between AD and environmental risk factors along with their mechanisms of action on the brain functions.

Modulation of the osteoconductive property and immune response of poly(ether ether ketone) by modification with calcium ions.

Both bone-forming cells and immune cells have pivotal roles in bone tissue repair. In this work, we prepared a Ca-modified poly(ether ether ketone) (PEEK) to enhance the osteoconductivity but mitigate immune response of cells. To modify Ca ions onto a chemically inert PEEK, PEEK was first coated with poly(norepinephrine) followed by soaking in Ca(OH)2 aqueous solution. Modification of Ca ions onto PEEK enhanced the proliferation and differentiation of MC3T3-E1 preosteoblast cells and human mesenchymal stem cells, but had no apparent effect on MLC-6 osteoclast-like cells. Naïve RAW264.7 macrophages cultured on pristine PEEK produced proinflammatory cytokines, but not on Ca-modified PEEK. Lipopolysaccharide-stimulated RAW264.7 macrophages on Ca-modified PEEK produced lower levels of proinflammatory cytokines but higher levels of anti-inflammatory cytokines compared with those on pristine PEEK. Lower levels of proinflammatory cytokines on Ca-modified PEEK were partially owing to higher interleukin-10 production mediated by Ca-activated pathways. Simple Ca modification of PEEK was shown to activate osteoblastic cell proliferation and differentiation, and shift macrophages towards an anti-inflammatory/wound healing type, which would be useful not only for bone tissue implants but also other implanted biomaterials.

Exploration of potential baker's yeast from sugarcane juice: optimization and evaluation.

The present study was carried out to explore baker's yeasts strains from sugarcane juice to assess its potential in laboratory scale production of breads. Collected juice samples were processed for isolation and identification of yeast strains based on standard cultural, morphological and biochemical characteristics. Among the six isolated strains, four (designated as S1, S2, S5 and S6) were identified as Saccharomyces cerevisiae and the rests (designated S3 and S4) were as S. rouxii. When assessing their CO2 production rates as a measure of their baking potential, S6 was found to produce maximum amount of gas (226.67 mm3 mL(-1)) in sucrose broth, whereas gas produced by S2, S1 and S5 were relatively insignificant (170, 136.67 and 86.67 mm3 mL(-1), respectively). No strain was found to produce undesirable H2S gas responsible for off-flavor. Besides, effects of different physicochemical parameters (e.g., pH, temperature, substrate concentration, incubation period, agitation etc.) on the production of yeast cell-mass were studied. Yield of cell mass was indirectly measured by spectrophotometric method at 550 nm. All the test isolates were found to produce maximum cell mass at a pH range of 4.0 to 5.0 in 2 to 4% molasses broth at 30 degrees C after 4 days of incubation. In the laboratory scale production of bread using composite flour, Isolate-S6 formed significant characteristic texture. Considering overall characteristics, Isolate- S6 was found to be satisfactorily potent for baking purpose.

Diabetes and impaired fasting glycemia in the tribes of Khagrachari hill tracts of Bangladesh.

OBJECTIVE: To determine the prevalence of type 2 diabetes and impaired fasting glycemia (IFG) in a tribal population of Bangladesh. RESEARCH DESIGN AND METHODS: A cluster sampling of 1,287 tribal subjects of age > or =20 years was investigated. They live in a hilly area of Khagrachari in the far northeast of Bangladesh. Fasting plasma glucose, blood pressure, height, weight, waist girth, and hip girth were measured. Lipid fractions were also estimated. We used the 1997 American Diabetes Association diagnostic criteria. RESULTS: The crude prevalence of type 2 diabetes was 6.6% and IFG was 8.5%. The age-standardized (20-70 years) prevalence of type 2 diabetes (95% CI) was 6.4% (4.96-7.87) and of IFG was 8.4% (6.48-10.37). Both tribesmen and women had equal risk for diabetes and IFG. Compared with the lower-income group, the participants with higher income had a significantly higher prevalence of type 2 diabetes (18.8 vs. 3.1%, P < 0.001) and IFG (17.2 vs. 4.3%, P < 0.001). Using logistic regression, we found that increased age, high-income group, and increased central obesity were the important risk factors of diabetes. CONCLUSIONS: The prevalence of diabetes in the tribal population was higher than that of the nontribal population of Bangladesh. Older age, higher central obesity, and higher income were proven significant risk factors of diabetes. High prevalence of diabetes among these tribes indicates that the prevalence of diabetes and its complications will continue to increase. Evidently, health professionals and planners should initiate diabetes care in these tribal communities.