Inhibition of TBL1 cleavage alleviates doxorubicin-induced cardiomyocytes death by regulating the Wnt/ß-catenin signal pathway.

AIMS: Doxorubicin (DOX) is a widely used anthracycline anticancer agent; however, its irreversible effects on the heart can result in DOX-induced cardiotoxicity (DICT) after cancer treatment. Unfortunately, the pathophysiology of DICT has not yet been fully elucidated, and there are no effective strategies for its prevention or treatment. In this investigation, the novel role of transducin beta-like protein 1 (TBL1) in developing and regulating DICT was explored. METHODS AND RESULTS: We observed a reduction in TBL1 protein expression levels as well as cleavage events in the transplanted cardiac tissues of patients diagnosed with Dilated Cardiomyopathy (DCM) and DICT. It was revealed that DOX selectively induces TBL1 cleavage at caspase-3 preferred sites-D125, D136, and D215. Interestingly, overexpression of the uncleaved TBL1 mutant (TBL1uclv) variant reduced apoptosis, effectively preventing DOX-induced cell death. We confirmed that cleaved TBL1 cannot form a complex with ß-catenin. As a result, Wnt reporter activity, and Wnt target gene expression collectively indicate a decrease in Wnt/ß-catenin signaling, leading to DICT progression. Furthermore, the cleaved TBL1 triggered DOX-induced abnormal electrophysiological features and disrupted calcium homeostasis. However, these effects were improved in TBL1uclv-overexpressing human-induced pluripotent stem cell-derived cardiomyocytes. Finally, in a DICT mouse model, TBL1uclv overexpression inhibited the DICT-induced reduction of cardiac contractility and collagen accumulation, ultimately protecting cardiomyocytes from cell death. CONCLUSIONS: Our findings reveal that the inhibition of TBL1 cleavage not only mitigates apoptosis but also enhances cardiomyocyte function, even in the context of DOX administration. Consequently, this study's results suggest that inhibiting TBL1 cleavage may be a novel strategy to ameliorate DICT.

Nobiletin regulates intracellular Ca2+ levels via IP3R and ameliorates neuroinflammation in Aß42-induced astrocytes.

Astrocytes are the major glial cells in the human brain and provide crucial metabolic and trophic support to neurons. The amyloid-ß peptide (Aß) alter the morphological and functional properties of astrocytes and induce inflammation and calcium dysregulation, contributing to Alzheimer's disease (AD) pathology. Recent studies highlight the role of Toll-like receptor (TLR) 4/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in inflammation. Reactive oxygen species (ROS) generated due to Aß, induce apoptosis in the brain cells worsening AD progression. Astrocytic cell surface receptors, such as purinergic receptors (P2Y1 and P2Y2), metabotropic glutamate receptor (mGLUR)5, α7 nicotinic acetylcholine receptor (α7nAChR), and N-methyl-d-aspartate receptors (NMDARs), have been suggested to interact with inositol trisphosphate receptor (IP3R) on the endoplasmic reticulum (ER) to induce Ca2+ movement from ER to cytoplasm, causing Ca2+ dysregulation. We found that the citrus flavonoid nobiletin (NOB) protected primary astrocytes from Aß42-induced cytotoxicity and inhibited TLR4/NF-κB signaling in Aß42-induced primary rat astrocytes. NOB was found to regulate Aß42-induced ROS levels through Keap1-Nrf2 pathway. The receptors P2Y1, P2Y2, mGLUR5, α7nAChR, and NMDARs induced intracellular Ca2+ levels by activating IP3R and NOB regulated them, thereby regulating intracellular Ca2+ levels. Molecular docking analysis revealed a possible interaction between NOB and IP3R in IP3R regulation. Furthermore, RNA sequencing revealed various NOB-mediated biological signaling pathways, such as the AD-presenilin, AD-amyloid secretase, and Wnt signaling pathway, suggesting possible neuroprotective roles of NOB. To conclude, NOB is a promising therapeutic agent for AD and works by modulating AD pathology at various levels in Aß42-induced primary rat astrocytes.

Evaluating the Efficiency of Black Soldier Fly (Hermetia illucens) Larvae in Converting Mackerel Head Waste into Valuable Resources.

The seafood processing industry generates significant waste, including mackerel heads (MH), constituting 20-32% of total waste. This study explored the potential of utilizing MH as a feed source for black soldier fly larvae (BSF larvae). BSF larvae are known for their ability to efficiently convert organic materials into nutrient-rich biomass. Five concentrations of MH (0, 10, 20, 30, 40, and 50% in chicken feed) were fed to BSF larvae for eight days. After harvesting, their growth, MH conversion efficiency, nutritional content, and heavy metals reduction potential were measured. BSF larvae showed optimal growth when fed with a feed containing 20% MH, resulting in a 14.36-fold increase in weight compared to the control group, as determined by the Fisher's Least Significant Difference Test. BSF larvae maintained a survival rate of 99.33%. With the lowest feed conversion ratio (FCR) of 2.09 at 20% MH, feed efficiency was improved by up to 65.15%, and feed reduction up to 73.53%. MH enhanced lipid and protein content in BSF larvae. Furthermore, BSF larvae in this study showed higher polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as other amino acids which are required for breeding animals. The current study highlights the potential of MH as a feed source for BSF larvae, improving nutritional biomass. It also suggests BSF larvae as an eco-friendly option for handling seafood processing waste and as an alternative feed source for animals.

Nutrition survey methods and food composition database update of the Korean Genome and Epidemiology Study.

This study presents the nutrition survey methods and the updated food composition database for the Korean Genome and Epidemiology Study (KoGES). The KoGES, which is the largest and longest cohort study in Korea, aims to identify genetic and environmental factors associated with chronic diseases. This study has collected dietary data using a validated semi-quantitative food frequency questionnaire and/or the 24-hour recall method. However, these dietary survey methods use different food composition databases, and their nutritional values are out of date. Therefore, it became necessary to update the food composition database by correcting errors in nutrient analysis values to reflect improvements in the performance of food ingredient analysis equipment, revising international values ​​to analysis values ​​of Korean agricultural products, adjusting nutrient units, and adding newly reported nutrients related to chronic diseases. For this purpose, we integrated the different food composition databases used in each nutrition survey, updated 23 nutrients, and expanded 48 new nutrients for 3,648 food items using the latest reliable food composition databases published by national and international institutions. This revised food composition database may help to clarify the relationship between various nutrients and chronic diseases. It could serve as a valuable resource for nutritional, epidemiological, and genomic research and provide a basis for determining public health policies.

1-Deoxynojirimycin containing Morus alba leaf-based food modulates the gut microbiome and expression of genes related to obesity.

BACKGROUND: Obesity is a serious disease with an alarmingly high incidence that can lead to other complications in both humans and dogs. Similar to humans, obesity can cause metabolic diseases such as diabetes in dogs. Natural products may be the preferred intervention for metabolic diseases such as obesity. The compound 1-deoxynojirimycin, present in Morus leaves and other sources has antiobesity effects. The possible antiobesity effect of 1-deoxynojirimycin containing Morus alba leaf-based food was studied in healthy companion dogs (n = 46) visiting the veterinary clinic without a history of diseases. Body weight, body condition score (BCS), blood-related parameters, and other vital parameters of the dogs were studied. Whole-transcriptome of blood and gut microbiome analysis was also carried out to investigate the possible mechanisms of action and role of changes in the gut microbiome due to treatment. RESULTS: After 90 days of treatment, a significant antiobesity effect of the treatment food was observed through the reduction of weight, BCS, and blood-related parameters. A whole-transcriptome study revealed differentially expressed target genes important in obesity and diabetes-related pathways such as MLXIPL, CREB3L1, EGR1, ACTA2, SERPINE1, NOTCH3, and CXCL8. Gut microbiome analysis also revealed a significant difference in alpha and beta-diversity parameters in the treatment group. Similarly, the microbiota known for their health-promoting effects such as Lactobacillus ruminis, and Weissella hellenica were abundant (increased) in the treatment group. The predicted functional pathways related to obesity were also differentially abundant between groups. CONCLUSIONS: 1-Deoxynojirimycin-containing treatment food have been shown to significantly improve obesity. The identified genes, pathways, and gut microbiome-related results may be pursued in further studies to develop 1-deoxynojirimycin-based products as candidates against obesity.

Healthy and Unhealthy Dietary Patterns of Depressive Symptoms in Middle-Aged Women.

Depressive symptoms are a common menopausal feature in middle-aged women and are associated with dietary factors. This study aimed to determine the association between dietary patterns and depressive symptoms in 2190 Korean women aged 45-69 years. Depressive symptoms were screened using the Beck Depression Inventory-II (BDI-II), and food intake was examined using a food frequency questionnaire. Dietary patterns were derived from principal components analysis and identified two dietary patterns: a "healthy" dietary pattern (high intake of whole-grain rice, legumes, vegetables, fruits, and fish) and an "unhealthy" dietary pattern (high intake of noodles, dumplings, sweets, red meat, soda, and coffee). After adjusting for all confounding factors, those with the highest healthy dietary pattern scores had a 0.56-fold lower risk of depressive symptoms than those with the lowest score (Odds Ratio (OR) = 0.56, 95% confidence interval (CI): 0.37-0.84, p for trend = 0.006). Conversely, those with the highest unhealthy pattern scores had a 1.85-fold higher risk of depressive symptoms than that of those in the lowest quartile (OR = 1.85, 95% CI: 1.30-2.63, p for trend = 0.002). In middle-aged women, a dietary pattern of high intake of fiber-rich whole-grain rice, fruits, vegetables, and legumes may help prevent and manage depressive symptoms.

The Bioactivity and Phytochemicals of Muscari comosum (Leopoldia comosa), a Plant of Multiple Pharmacological Activities.

Leopoldia comosa (LC), popularly known as Muscari comosum, spontaneously grows in the Mediterranean region and its bulbs are used as a vegetable. Traditionally, they are also used to treat various diseases and conditions, which has inspired the study of the pharmacological activities of different parts of LC. These studies revealed the numerous biological properties of LC including antioxidant, anti-inflammatory, anti-diabetes, anti-obesity, anti-cancer, anti-Alzheimer's disease, antibacterial, and immune stimulant. High antioxidant activity compared to other non-cultivated plants, and the potential role of antioxidant activity in other reported activities make LC an excellent candidate to be developed as an antioxidant plant against important associated diseases. The presence of a diverse class of phytochemicals (n = 85), especially flavonoids and homoisoflavones, in LC, also imparts significance to the nutraceutical candidature of the plant. However, limited animal studies and the lack of a directional approach have limited the further design of effective clinical studies for the development of LC. The current study is the first attempt to comprehensively compile information regarding the phytochemicals and pharmacological activities of LC, emphasize the targets/markers targeted by LC, important in other activities, and also highlight the current gaps and propose possible bridges for the development of LC as a therapeutic and/or supplement against important diseases.

An Update on the Chemical Constituents and Biological Properties of Selected Species of an Underpinned Genus of Red Algae: Chondrus.

Macroalgae, particularly red seaweeds, have attracted significant attention due to their economic and health benefits. Chondrus, a red algae genus, despite its economic importance, seems to be undervalued. Among all its species, Chondrus crispus has been meticulously documented for its biological properties, and little is known about other species. No comprehensive review of the biological properties of this genus has been acknowledged. Thus, this review aimed to summarize the available information on the chemical constituents and biological properties of a few selected species, including Chondrus crispus, Chondrus ocellatus, Mazzaella canaliculata, and Chondrus armatus. We compiled and discovered that the genus is offering most of the important health-promoting benefits evidenced from in vitro and in vivo studies focused on antimicrobial, immunomodulation, neuroprotection, anti-atopic, anti-inflammatory, anti-viral, anti-diabetic, cytoprotective, antioxidant, anti-coagulation, nephroprotective, anti-tumor, and anti-venom activity, which speaks about the potential of this genus. Data on clinical studies are limited. Further, around 105 chemical constituents have been reported from Chondrus spp. Given its significance, further investigation is warranted, in the form of meticulously planned cell, animal, and clinical studies that concentrate on novel health-enhancing endeavors, in order to unveil the full potential of this genus. The review also outlines challenges and future directions.

Comparative study on estrogen receptor alpha dimerization and transcriptional activity of parabens.

Parabens are used as preservatives in various household products, including oral products, cosmetics, and hair/body washes. In recent years, the widespread use of parabens has raised concerns due to the potential health risks associated with their estrogenic effects. In the present study, we evaluated and compared the estrogenic activity of parabens using two cell-based in vitro tests: (1) bioluminescence resonance energy transfer (BRET)-based estrogen receptor alpha (ERα) dimerization using HEK293 cells that were stably transfected with ERα-fused NanoLuc luciferase (Nluc) and HaloTag (HT) expression vector, and (2) stably transfected transcriptional activation (STTA) assays using ERα-HeLa9903 cells. The following parabens were tested using the BRET-based ERα dimerization assay and showed estrogenic activity (PC20 values): methyl paraben (MP, 5.98 × 10-5 M), ethyl paraben (EP, 3.29 × 10-5 M), propylparaben (PP, 3.09 × 10-5 M), butyl paraben (BP, 2.58 × 10-5 M), isopropyl paraben (IsoPP, 1.37 × 10-5 M), and isobutyl paraben (IsoBP, 1.43 × 10-5 M). Except MP, all other parabens tested using the STTA assay also showed estrogenic activity: EP, 7.57 × 10-6 M; PP, 1.18 × 10-6 M; BP, 3.02 × 10-7 M; IsoPP, 3.58 × 10-7 M; and IsoBP, 1.80 × 10-7 M. Overall, EP, PP, BP, IsoPP, and IsoBP tested positive for estrogenic activity using both assays. These findings demonstrate that most parabens, albeit not all, induce ERα dimerization and possess estrogenic activity.

Cyanidin-3-O-glucoside protects the brain and improves cognitive function in APPswe/PS1ΔE9 transgenic mice model.

Cyanidin-3-O-glucoside (C3G) is a natural anthocyanin with antioxidant, anti-inflammatory, and antitumor properties. However, as the effects of C3G on the amyloidogenic pathway, autophagy, tau phosphorylation, neuronal cell death, and synaptic plasticity in Alzheimer's disease models have not been reported, we attempted to investigate the same in the brains of APPswe/PS1ΔE9 mice were analyzed. After oral administration of C3G (30 mg/kg/day) for 16 weeks, the cortical and hippocampal regions in the brains of APPswe/PS1ΔE9 mice were analyzed. C3G treatment reduced the levels of soluble and insoluble Aß (Aß40 and Aß42) peptides and reduced the protein expression of the amyloid precursor protein, presenilin-1, and ß-secretase in the cortical and hippocampal regions. And C3G treatment upregulated the expression of autophagy-related markers, LC3B-II, LAMP-1, TFEB, and PPAR-α and downregulated that of SQSTM1/p62, improving the autophagy of Aß plaques and neurofibrillary tangles. In addition, C3G increased the protein expression of phosphorylated-AMPK/AMPK and Sirtuin 1 and decreased that of mitogen-activated protein kinases, such as phosphorylated-Akt/Akt and phosphorylated-ERK/ERK, thus demonstrating its neuroprotective effects. Furthermore, C3G regulated the PI3K/Akt/GSK3ß signaling by upregulating phosphorylated-Akt/Akt and phosphorylated-GSK3ß/GSK3ß expression. C3G administration mitigated tau phosphorylation and improved synaptic function and plasticity by upregulating the expression of synapse-associated proteins synaptophysin and postsynaptic density protein-95. Although the potential of C3G in the APPswe/PS1ΔE9 mouse models has not yet been reported, oral administration of the C3G is shown to protect the brain and improve cognitive behavior.

An eight-week randomized intervention study on Korean adults to evaluate the effect of milk intake on obesity.

The anti-obesity effect of milk intake has been suggested via a variety of designed studies, but findings of obesity interventions for Korean adults are scarcely reported. The study aimed to investigate the anti-obesity effect of cow milk in Korean adults with an 8-wk randomized intervention. A total of 121 adults overweight aged 19 to 60 yr old were randomly assigned to 1 of the 2 groups: milk or control. During the intervention, both groups were encouraged 500 kcal of restriction a day, and the milk group consumed 200 mL of milk twice a day; the same energy intake as the control group, including milk intake, was recommended for 8 wk. We detected no significant differences in body weight (BW) and body mass index (BMI) between the milk and control groups during the 8-wk intervention, although the changes in BW and BMI of those within the milk group were significant. High-density lipoprotein cholesterol levels and serum calcium levels increased significantly in the milk group compared with the control group. Calcium, phosphorus, vitamin A, and riboflavin intakes increased significantly, when compared with the control. In conclusion, 8-wk milk consumption had no effect on weight loss and BMI change but improved some blood biomarkers and nutrient intake in Korean adults who were overweight. To evaluate the effect of milk on obesity reduction, well-designed, long-term, and large-scale studies are needed.

Statistical methods for handling nondetected results in food chemical monitoring data to improve food risk assessments.

Chemical risk assessment is important for risk management, and estimates of chemical exposure must be as accurate as possible. Chemical concentrations in food below the limit of detection are known as nondetects and result in left-censored data. During statistical analysis, the method used for handling values below the limit of detection is important. Many risk assessors employ widely used substitution methods to treat left-censored data, as recommended by international organizations. The National Institute of Food and Drug Safety Evaluation of South Korea also recommends these methods, which are currently used for chemical exposure assessments. However, these methods have statistical limitations, and international organizations recommend more advanced alternative statistical approaches. In this study, we assessed the validity of currently used statistical methods for handling nondetects. To identify the most suitable statistical method for handling nondetection, we created virtual data and conducted simulation studies. Based on both simulation and case studies, the Maximum Likelihood Estimation (MLE) and Robust Regression on Order Statistics (ROS) methods were found to be the best options. The statistical values obtained from these methods were similar to those obtained from the commonly used 1/2 Limit of Detection (LOD) substitution method for nondetection treatment. In three case studies, we compared the various methods based on the root mean squared error. The data for all case studies were from the same source, to avoid heterogeneity. Across various sample sizes and nondetection rates, the mean and 95th percentile values for all treatment methods were similar. However, "lognormal maximum likelihood estimation" method was not suitable for estimating the mean. Risk assessors should consider statistical processing of monitoring data to reduce uncertainty. Currently used substitution methods are effective and easy to apply to large datasets with nondetection rates <80%. However, advanced statistical methods are required in some circumstances, and national guidelines are needed regarding their use in risk assessments.

Impact of probiotics on cognition and constipation in the elderly: A meta-analysis.

Cognitive decline and constipation are common complications in the elderly. Probiotics are potential therapeutic agents to ameliorate cognitive impairment through gut-brain axis. Several clinical studies have investigated the beneficial effects of probiotics on cognitive impairment and constipation in elderly. However, a quantitative meta-analysis is required to evaluate the efficacy of probiotics on cognitive function and constipation. Thirteen clinical studies were included in this meta-analysis. We examined the risk of bias assessment and heterogeneity of eight studies for cognition and five studies for constipation, followed by group and subgroup meta-analyses using a random-effects model to evaluate the potential of probiotic supplements on cognition function and constipation in aged people. The results of the pooled meta-analysis revealed that probiotic supplementation did not improve the cognitive rating scale assessment for all studies (estimate = 0.13; 95%CI [-0.18, 0.43]; p = 0.41; I2 = 83.51%). However, subgroup analysis of single strain supplementation showed improved cognitive function in elderly people (estimate = 0.35; 95%CI [0.02, 0.69]; p = 0.039; I2 = 19.19%) compared to multiple strains. Probiotics also enhanced defecation frequency in constipated patients (estimate = 0.27; 95%CI [0.05, 0.5]; p = 0.019; I2 = 67.37%). Furthermore, probiotic supplementation resulted in higher fecal Lactobacillus counts than placebo (estimate = 0.37; 95%CI [0.05, 0.69]; p = 0.026; I2 = 21.3%). Subgroup analysis indicated that a probiotic intervention period of ≥4 weeks was more effective (estimate = 0.35; 95%CI [0.01, 0.68]; p = 0.044; I2 = 0%) in reducing constipation symptoms than a short intervention duration. Based on these results, probiotic supplementation could be a potential intervention to reduce constipation symptoms in the elderly population. The heterogeneity between studies is high, and limited trials are available to evaluate the cognitive function of aged individuals using probiotics. Therefore, further studies are required to determine the effect of probiotics on cognition.

Stevia (Stevia rebaudiana) extract ameliorates insulin resistance by regulating mitochondrial function and oxidative stress in the skeletal muscle of db/db mice.

BACKGROUND: Type 2 diabetes mellitus (T2DM), a growing health problem worldwide, is a metabolic disorder characterized by hyperglycemia due to insulin resistance and defective insulin secretion by pancreatic ß-cells. The skeletal muscle is a central organ that consumes most of the insulin-stimulated glucose in the body, and insulin resistance can damage muscles in T2DM. Based on a strong correlation between diabetes and muscles, we investigated the effects of stevia extract (SE) and stevioside (SV) on the skeletal muscle of diabetic db/db mice. METHODS: The mice were administered saline, metformin  (200 mg/kg/day), SE (200 and 500 mg/kg/day), and SV (40 mg/kg/day) for 35 days. During administration, we checked the levels of fasting blood glucose twice a week and conducted the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). After administration, we analyzed serum biochemical parameters, triglyceride (TG), total cholesterol (TC), insulin and antioxidant enzymes, and the cross-sectional area of skeletal muscle fibers of db/db mice. Western blots were conducted using the skeletal muscle of mice to examine the effect of SE and SV on protein expression of insulin signaling, mitochondrial function, and oxidative stress. RESULTS: SE and SV administration lowered the levels of fasting blood glucose, OGTT, and ITT in db/db mice. The administration also decreased serum levels of TG, TC, and insulin while increasing those of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Interestingly, muscle fiber size was significantly increased in db/db mice treated with SE500 and SV. In the skeletal muscle of db/db mice, SE and SV administration activated insulin signaling by increasing the protein expression of insulin receptor substrate, Akt, and glucose transporter type 4. Furthermore, SE500 administration markedly increased the protein expression of AMP-activated protein kinase-α, sirtuin-1, and peroxisome proliferator-activated receptor-γ coactivator-1α. SV administration significantly reduced oxidative stress by down-regulating the protein expression of 4-hydroxynonenal, heme oxygenase-1, SOD, and GPx. In addition, SE500 and SV administration suppressed the expression of apoptosis-related proteins in the skeletal muscle of db/db mice. CONCLUSION: SE and SV administration attenuated hyperglycemia in diabetic mice. Moreover, the administration ameliorated insulin resistance by regulating mitochondrial function and oxidative stress, increasing muscle fiber size. Overall, this study suggests that SE and SV administration may serve as a potential strategy for the treatment of diabetic muscles.

Carbon Dots for the Treatment of Inflammatory Diseases: An Appraisal of In Vitro and In Vivo Studies.

In recent decades, several studies demonstrating various applications of carbon dots (C-dots), including metal sensing, bioimaging, pH sensing, and antimicrobial activities, have been published. Recent developments have shifted this trend toward biomedical applications that target various biomarkers relevant to chronic diseases. However, relevant developments and research results regarding the anti-inflammatory properties of C-dots against inflammation-associated diseases have not been systematically reviewed. Hence, this review discusses the anti-inflammatory effects of C-dots in in vivo and in vitro models of LPS-induced inflammation, gout, cartilage tissue engineering, drug-induced inflammation, spinal cord injury, wound healing, liver diseases, stomach cancer, gastric ulcers, acute kidney and lung injury, psoriasis, fever or hypothermia, and bone tissue regeneration. The compiled studies demonstrate the promising potential of C-dots as anti-inflammatory agents for the development of new drugs.

Postbiotics against Obesity: Perception and Overview Based on Pre-Clinical and Clinical Studies.

Overweight and obesity are significant global public health concerns that are increasing in prevalence at an alarming rate. Numerous studies have demonstrated the benefits of probiotics against obesity. Postbiotics are the next generation of probiotics that include bacteria-free extracts and nonviable microorganisms that may be advantageous to the host and are being increasingly preferred over regular probiotics. However, the impact of postbiotics on obesity has not been thoroughly investigated. Therefore, the goal of this review is to gather in-depth data on the ability of postbiotics to combat obesity. Postbiotics have been reported to have significant potential in alleviating obesity. This review comprehensively discusses the anti-obesity effects of postbiotics in cellular, animal, and clinical studies. Postbiotics exert anti-obesity effects via multiple mechanisms, with the major mechanisms including increased energy expenditure, reduced adipogenesis and adipocyte differentiation, suppression of food intake, inhibition of lipid absorption, regulation of lipid metabolism, and regulation of gut dysbiosis. Future research should include further in-depth studies on strain identification, scale-up of postbiotics, identification of underlying mechanisms, and well-defined clinical studies. Postbiotics could be a promising dietary intervention for the prevention and management of obesity.

Biogenic silver NPs alleviate LPS-induced neuroinflammation in a human fetal brain-derived cell line: Molecular switch to the M2 phenotype, modulation of TLR4/MyD88 and Nrf2/HO-1 signaling pathways, and molecular docking analysis.

Silver nanoparticles (AgNPs) have inconsistent findings against inflammation. Although a wealth of literature on the beneficial effects of green-synthesized AgNPs has been published, a detailed mechanistic study of green AgNPs on the protective effects against lipopolysaccharide (LPS)-induced neuroinflammation using human microglial cells (HMC3) has not yet been reported. For the first time, we studied the inhibitory effect of biogenic AgNPs on inflammation and oxidative stress induced by LPS in HMC3 cells. X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and transmission electron microscopy were used to characterize AgNPs produced from honeyberry. Co-treatment with AgNPs significantly reduced mRNA expressions of inflammatory molecules such as interleukin (IL)-6 and tumor necrosis factor-α, while increasing the expressions of anti-inflammatory markers such as IL-10 and transforming growth factor (TGF)-ß. HMC3 cells were also switched from M1 to M2, as shown by lower expression of M1 markers such as cluster of differentiation (CD)80, CD86, and CD68 and higher expression of M2 markers such as CD206, CD163, and triggering receptors expressed on myeloid cells (TREM2). Furthermore, AgNPs inhibited LPS-induced toll-like receptor (TLR)4 signaling, as evidenced by decreased expression of myeloid differentiation factor 88 (MyD88) and TLR4. In addition, AgNPs reduced the production of reactive oxygen species (ROS) and enhanced the expression of nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), while decreasing the expression of inducible nitric oxide synthase. The docking score of the honeyberry phytoconstituents ranged from -14.93 to - 4.28 KJ/mol. In conclusion, biogenic AgNPs protect against neuroinflammation and oxidative stress by targeting TLR4/MyD88 and Nrf2/HO-1 signaling pathways in a LPS-induced in vitro model. Biogenic AgNPs could be utilized as potential nanomedicine against LPS-induced inflammatory disorders.

Recent Clinical Advances on Long Non-Coding RNAs in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a more aggressive type of breast cancer due to its heterogeneity and complex molecular mechanisms. TNBC has a high risk for metastasis, and it is difficult to manage clinical conditions of the patients. Various investigations are being conducted to overcome these challenges using RNA, DNA, and proteins for early diagnosis and treatment. Recently, long non-coding RNAs (lncRNAs) have emerged as a novel target to treat the multistep process of TNBC. LncRNAs regulate epigenetic expression levels, cell proliferation and apoptosis, and tumour invasiveness and metastasis. Thus, lncRNA-based early diagnosis and treatment options could be helpful, especially for patients with severe TNBC. lncRNAs are expressed in a highly specific manner in cells and tissues and are involved in TNBC progression and development. lncRNAs could be used as sensitive and specific targets for diagnosis, treatment, and monitoring of patients with TNBC. Therefore, the exploration of novel diagnostic and prognostic biomarkers is of extreme importance. Here, we discuss the molecular advances on lncRNA regulation of TNBC and lncRNA-based early diagnosis, treatment, and drug resistance.

Pharmacological Activities of Mogrol: Potential Phytochemical against Different Diseases.

Recently, mogrol has emerged as an important therapeutic candidate with multiple potential pharmacological properties, including neuroprotective, anticancer, anti-inflammatory, antiobesity, antidiabetes, and exerting a protective effect on different organs such as the lungs, bone, brain, and colon. Pharmacokinetic studies also highlighted the potential of mogrol as a therapeutic. Studies were also conducted to design and synthesize the analogs of mogrol to achieve better activities against different diseases. The literature also highlighted the possible molecular mechanism behind pharmacological activities, which suggested the role of several important targets, including AMPK, TNF-α, and NF-κB. These important mogrol targets were verified in different studies, indicating the possible role of mogrol in other associated diseases. Still, the compilation of pharmacological properties, possible molecular mechanisms, and important targets of the mogrol is missing in the literature. The current study not only provides the compilation of information regarding pharmacological activities but also highlights the current gaps and suggests the precise direction for the development of mogrol as a therapeutic against different diseases.