Background: Magnocurarine is an alkaloid isolated from several traditional Asian medicinal plants, including Magnolia and Harrisonia species. Previous studies have reported its anti-nociceptive, anti-inflammatory, and antimicrobial activities with relatively low cytotoxicity. However, the anticancer activity of magnocurarine, particularly its effects on prostate cancer cell migration and invasion, has not been well characterized. Objective: This study aims to investigate the effects of magnocurarine on the migration and invasion of castration-resistant prostate cancer (CRPC) cells. Methods: DU145 and PC3 cells were treated with non-toxic concentrations of magnocurarine (0-40 µM), and migration and invasion capabilities were evaluated using scratch wound healing and transwell invasion assays, gelatin zymography, and western blot analysis. Results: Magnocurarine significantly reduced the migration and invasion of CRPC cells in a dose-dependent manner (p < 0.05). The inhibitory effects were associated with decreased activities of MMP-2 and MMP-9, together with reduced expression of invasion-related proteins including uPA, uPAR, and MT1-MMP. In addition, magnocurarine suppressed the expression of mesenchymal markers, including N-cadherin, vimentin, and fibronectin. Further investigation showed that magnocurarine decreased the phosphorylation of ERK, JNK, and p38 without altering total protein expression, suggesting suppression of MAPK signaling activation. Conclusion: These findings indicate that magnocurarine attenuates migratory and invasive phenotypes in CRPC cells and is associated with reduced activation of MAPK signaling. This study provides initial evidence supporting the anti-migratory and anti-invasive effects of magnocurarine in prostate cancer cells and suggests its potential for further investigation as a phytochemical-derived drug candidate in advanced prostate cancer.

Background/Objectives: Oligofructans are a category of non-digestible carbohydrates with beneficial effects on gut health and microbiota modulation. In this study, oligofructans were produced from raw sugar using Bacillus subtilis TISTR 001, and their safety and effects on the gut microbiota were assessed in rats. Methods: The acute toxicity assessment consisted of administering a single oral dose of 2000 mg/kg body weight (bw), whereas the subchronic toxicity assessment included oral dosages of 200, 600, and 2000 mg/kg/day for 90 days. Results: In the acute toxicity test, no mortality or toxicity was observed in the rats treated with a single dose of oligofructans during the 14-day observation period. The median lethal dose (LD50) of the oligofructans was >2000 mg/kg bw. In the subchronic toxicity study, daily oligofructans doses of 200, 600, and 2000 mg/kg bw for 90 days did not cause lethality or toxic clinical symptoms in rats of either sex. Furthermore, no treatment-related adverse effects of oligofructans on the hematological and biochemical parameters or organ histopathology were observed in the treatment and satellite groups. Hence, the no-observed-adverse-effect level (NOAEL) of oligofructans under the study's test conditions was confirmed as 2000 mg/kg/day. Conclusion: No adverse effects were observed in either acute or subchronic toxicity studies at doses up to 2000 mg/kg/day. Moreover, oligofructans modulated the gut microbiota by promoting the growth of potentially beneficial commensal bacteria and reducing the taxa associated with inflammation or metabolic dysfunction. However, further studies are required to confirm these microbiome-related changes in humans.

Metastasis remains the leading cause of death among patients with non-small cell lung cancer (NSCLC), emphasizing the urgent need for safer and more effective therapeutic options. Mitogen-activated protein kinase (MAPK) pathways play a crucial role in regulating EMT, migration, and invasion in NSCLC. Targeting these molecular mechanisms has become a key strategy in inhibiting NSCLC metastasis. Loureirin A and Loureirin B, flavonoids derived from the Thai traditional herb Dracaena loureiri, have shown potential pharmacological effects; however, their roles in NSCLC metastasis remain unexplored. This study aimed to elucidate the mechanisms by which Loureirin A and Loureirin B suppress EMT, migration, and invasion in NSCLC cells via the MAPK signaling pathway. The sulforhodamine B (SRB) assay showed that Loureirin A and Loureirin B, at concentrations ranging from 0 to 140 μM, were non-toxic to both A549 and H1299 cells. Additionally, Loureirins A and B exhibited no cytotoxic effects on primary human dermal fibroblast cells and did not induce hemolysis in red blood cells (RBCs). The wound-healing and trans-well assays were used to evaluate the anti-migratory and anti-invasion properties of Loureirin A and Loureirin B in NSCLC cell lines. Gelatin zymography was employed to investigate the activity of MMP-2 (gelatinase A) and MMP-9 (gelatinase B), while Western blot analysis was used to examine the expression of EMT markers and invasive proteins, and the phosphorylation of MAPK signaling molecules. Our results demonstrate that both Loureirin A and Loureirin B significantly suppressed the migration and invasion of A549 and H1299 cells. These compounds suppressed the activity of matrix metalloproteinases MMP-2 and MMP-9 and downregulated the expression of key invasive proteins including uPA, uPAR, and MT1-MMP. Additionally, they effectively suppressed the expression of EMT markers such as N-cadherin, Vimentin, and Fibronectin. Mechanistically, Loureirin A and Loureirin B inhibited the MAPK signaling pathway by downregulating the phosphorylation of ERK, JNK, and p38 proteins. In conclusion, these findings demonstrate that Loureirin A and Loureirin B exhibit potent anti-invasive properties and no cytotoxic effect on NSCLC cell lines, suggesting their potential as promising candidates for anti-cancer drug development. Furthermore, they may pave the way for the exploration of combination therapies with other anti-cancer drugs for clinical translation.

Can black soldier fly (BSF) larvae be a protein substitute for managing adverse food reactions (AFRs) in dogs, specifically those with dermatitis? We evaluated BSF larvae’s safety, tolerance, and effectiveness as a novel protein source in dogs with AFRs. Sixteen dogs, including eight healthy controls and eight diagnosed with AFRs, were fed a diet containing BSF larvae for four weeks. Skin conditions, including dermatological lesions and Pruritus Visual Analog Scale (PVAS) scores, and gastrointestinal signs, including relevant clinical signs, stool consistency, and hematological and biochemical parameters, were monitored. No significant gastrointestinal side effects were observed. The control and AFRs groups maintained stable body weights, while stool consistency scores did not change significantly. Moreover, skin reaction data obtained before the study were collected through interviews with the owners. The mean PVAS scores in the AFRs group were significantly higher (p < 0.05) during the self-control period (6.0 ± 1.6) when compared with other periods. However, no significant differences (p > 0.05) were observed between the pre-study baseline (2.0 ± 1.1) and scores at 2 weeks (2.3 ± 1.5) and 4 weeks (2.4 ± 1.2) of feeding with BSF-based food, which indicated that BSF larvae did not exacerbate pruritic symptoms. Hematology and blood chemistry remained within normal ranges in all dogs, indicating no adverse effects on overall health. BSF larvae were well tolerated by AFR-affected and control dogs, with no adverse clinical outcomes. The findings suggest that BSF larvae may offer a better, sustainable alternative protein source for managing AFRs in dogs, particularly in those on hypoallergenic diets. Further long-term studies are needed to confirm these results and assess the broader implications of BSF larvae diets on canine health.

Turmeric (Curcuma longa) and Indian gooseberry (Phyllanthus emblica) are widely used for their ethnopharmacological properties, particularly in ASEAN countries. Recently, our group has formulated Thai rice instant granules containing turmeric extract and P. emblica fruit pulp (TR instant granules); however, their toxicity profile has not been evaluated. This study investigated the long-term safety of TR instant granules in rats and assessed their effect on hepatic antioxidant status. Oral administration at doses of 200, 600, and 2,000 mg/kg body weight for 180 days resulted in no toxic effects, behavioral changes, mortality, or alterations in organ weights or hematological parameters. Significant changes were observed in biochemical markers, but there were no histopathological abnormalities. TR instant granules significantly upregulated hepatic antioxidant genes (Nrf2, GPx, CAT, GR, SOD, and HO-1). Phytochemical analysis identified chlorogenic acid and curcumin as major constituents. In silico molecular docking demonstrated that these compounds strongly bind multiple antioxidant enzymes and the Nrf2–Keap1 complex, supporting their potential as effective modulators of cellular antioxidant defenses. Overall, long-term administration of TR instant granules is safe and may enhance antioxidant mechanisms in rats. These findings support the potential development of TR instant granules as a safe functional food or nutraceutical with antioxidant benefits.

Background/Objectives: Chronic lower respiratory tract inflammation can result from exposure to bacterial particles, leading to the activation of the NLRP3 inflammasome pathway. These effects may cause irreversible respiratory damage, contributing to persistent lung injury and chronic obstructive pulmonary disease (COPD), as observed in long COVID or bacterial pneumonia in older adults’ patients. Given its profound impact, the NLRP3 inflammasome has emerged as a key therapeutic target for mitigating aberrant inflammatory responses. Methods: In this study, we investigated the anti-inflammatory effects of Kum Akha black rice, a functional food, on the attenuation of NLRP3 inflammasome pathway using lipopolysaccharide-induced A549 lung epithelial cells and a C57BL/6NJcl mouse model. The anthocyanin-rich fraction from Kum Akha black rice germ and bran extract (KA1-P1) was obtained using a solvent-partitioned extraction technique. Results: KA1-P1 exhibited a high anthocyanin content (74.63 ± 1.66 mg/g extract) as determined by the pH differential method. The HPLC analysis revealed cyanidin-3-O-glucoside (C3G: 45.58 ± 0.48 mg/g extract) and peonidin-3-O-glucoside (P3G: 6.92 ± 0.29 mg/g extract) as its anthocyanin’s active compounds. Additionally, KA1-P1 demonstrated strong antioxidant activity, as assessed by DPPH and ABTS assays. KA1-P1 (12.5–100 μg/mL) possessed inhibitory effects on LPS + ATP-induced A549 lung cells inflammation through the significant suppressions of NLRP3, IL-6, IL-1β, and IL-18 mRNA levels and the inhibition of cytokine secretions in a dose-dependent manner (p < 0.05). Mechanistic analysis revealed that KA1-P1 downregulated key proteins in the NLRP3 inflammasome pathway (NLRP3, ASC, pro-caspase-1, and cleaved-caspase-1). Furthermore, in vivo studies demonstrated that KA1-P1 significantly diminished LPS-induced lower respiratory inflammation in C57BL/6NJcl mice, as evidenced by the reduced bronchoalveolar lavage fluid and blood levels of inflammatory cytokines (IL-6, IL-1β, and IL-18) and diminished histopathological inflammatory lung lesions. Conclusions: Overall, our findings suggest that the anti-inflammatory properties of KA1-P1 may support its application as a functional supplement or promote the consumption of pigmented rice among the elderly to mitigate chronic lower respiratory tract inflammation mediated by the NLRP3 inflammasome pathway.

The COVID-19-related long-standing effect or Post-Acute Sequelae of COVID-19 (PASC) is often associated with NLRP3 inflammasome activation in pulmonary inflammation elicited by SARS-CoV-2 spike proteins. Spike proteins engage toll-like receptors (TLRs) in respiratory epithelial cells, leading to excessive cytokine production. Given the need for effective therapeutic strategies to mitigate spike protein-stimulated lung inflammation, we examined the anti-inflammatory properties of luteolin and ethanolic extract from Harrisonia perforata (Blanco) Merr. root. The ethanolic extract of H. perforata root (HPEE) contained a high concentration of luteolin flavonoid (143.53 ± 1.58 mg/g extract). Both HPEE (25–100 μg/mL) and luteolin (4.5–36 μM) significantly inhibited inflammation stimulated by the Wuhan (W) and Omicron (O) spike protein S1, as evidenced by a dose-dependent significant decrease in IL-6, IL-1β, and IL-18 secretion in A549 lung epithelial cells (p < 0.05). Furthermore, pretreatment with HPEE or luteolin prior to spike protein exposure (100 ng/mL) significantly, in a dose-dependent manner, repressed the inflammatory mRNA expression (p < 0.05). Mechanistic study revealed that HPEE and luteolin suppressed NLRP3 inflammasome signaling activation by reducing their machinery protein expressions. Additionally, they inhibited the ERK/JNK/p38 MAPK signaling activation, resulting in decreased inflammatory mRNA expression and cytokine release. These findings suggest that H. perforata root extract and its major flavonoid luteolin exert potent anti-inflammatory effects and may offer therapeutic potential against spike protein-induced lung inflammation.

Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths globally, with a persistently low five-year survival rate of only 14–17%. High rates of metastasis contribute significantly to the poor prognosis of NSCLC, in which inflammation plays an important role by enhancing tumor growth, angiogenesis, and metastasis. Targeting inflammatory pathways within cancer cells may thus represent a promising strategy for inhibiting NSCLC metastasis. This study evaluated the anti-inflammatory and anti-metastatic properties of morin, a bioactive compound derived from a Thai medicinal herb, focusing on its effects on NLRP3 inflammasome-mediated pathways in an in vitro NSCLC model. The A549 and H1299 cell lines were stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP) to activate the NLRP3 pathway. The inhibition effects exhibited by morin in reducing pro-inflammatory secretion in LPS- and ATP-stimulated NSCLC cells were assessed by ELISA, while wound healing and trans-well invasion assays evaluated its impact on cell migration and invasion. RT-qPCR measurement quantified the expression of inflammatory genes, and zymography and Western blotting were used to examine changes in invasive protein levels, epithelial-to-mesenchymal transition (EMT) markers, and underlying molecular mechanisms. Our findings demonstrated the significant ability of morin to decrease the production of IL-1β, IL-18, and IL-6 in a dose-dependent manner (p < 0.05), as well as suppress NSCLC cell migration and invasion. Morin downregulated invasive proteins (MMP-2, MMP-9, u-PAR, u-PA, MT1-MMP) and EMT markers (fibronectin, N-cadherin, vimentin) (p < 0.01) while also reducing the mRNA levels of NLRP3, IL-1β, IL-18, and IL-6. Mechanistic investigations revealed that morin suppressed NLRP3 inflammasome activity and inactivated MAPK pathways. Specifically, it decreased the expression of NLRP3 and ASC proteins and reduced caspase-1 activity, while reducing the phosphorylation of ERK, JNK, and p38 proteins. Collectively, these findings suggest that morin’s inactivation of the NLRP3 inflammasome pathway could offer a novel therapeutic strategy for counteracting pro-tumorigenic inflammation and metastatic progression in NSCLC.

Background/Objectives: The global SARS-CoV-2 outbreak has escalated into a critical public health emergency, with the spike glycoprotein S1 subunit of SARS-CoV-2 (spike-S1) linked to inflammation in lung tissue and immune cells. Luteolin, a flavone with anti-inflammatory properties, shows promise, but research on its effectiveness against long-COVID-related inflammation and spike protein-induced responses remains limited. This study aims to elucidate the underlying mechanisms of inflammation in THP-1 cells induced by the spike-S1. Additionally, it seeks to assess the potential of luteolin in mitigating inflammatory responses induced by the spike-S1 in a THP-1 macrophage model. Methods: The gene expression profiles of spike-S1 in THP-1 cells were analyzed by transcriptome sequencing. The inhibitory effect of luteolin on ER stress and inflammation in spike-S1-induced THP-1 cells was investigated using Western blotting, RT-PCR, and ELISA. Results: The candidate genes (CAMK2A, SIGLEC7, PPARGC1B, SEC22B, USP28, IER2, and TIRAP) were upregulated in the spike-S1-induced THP-1 group compared to the control group. Among these, calcium/calmodulin-dependent protein kinase II alpha (CAMK2A) was identified as the most promising molecule in spike-S1-induced THP-1 cells. Our results indicate that the spike S1 significantly increased the expression of ER-stress markers at both gene and protein levels. Luteolin significantly reduced ER stress by decreasing the expression of ER-stress marker genes and ER-stress marker proteins (p < 0.01). Additionally, luteolin exhibited anti-inflammatory properties upon spike S1-induction in THP-1 cells by significantly suppressing IL-6, IL-8, and IL-1β cytokine secretion in a dose-dependent manner (p < 0.05). Furthermore, our results revealed that luteolin exhibited the downregulation of the MAPK pathway, as evidenced by modulating the phosphorylation of p-ERK1/2, p-JNK and p-p38 proteins (p < 0.05). Conclusions: The results from this study elucidate the mechanisms by which the spike S1 induces inflammation in THP-1 cells and supports the use of naturally occurring bioactive compounds, like luteolin, against inflammation-related SARS-CoV-2 infection.

The COVID-19 pandemic, caused by SARS-CoV-2, poses a significant global health threat. The spike glycoprotein S1 of the SARS-CoV-2 virus is known to induce the production of pro-inflammatory mediators, contributing to hyperinflammation in COVID-19 patients. Triphala, an ancient Ayurvedic remedy composed of dried fruits from three plant species—Emblica officinalis (Family Euphorbiaceae), Terminalia bellerica (Family Combretaceae), and Terminalia chebula (Family Combretaceae)—shows promise in addressing inflammation. However, the limited water solubility of its ethanolic extract impedes its bioavailability. In this study, we aimed to develop nanoparticles loaded with Triphala extract, termed “nanotriphala”, as a drug delivery system. Additionally, we investigated the in vitro anti-inflammatory properties of nanotriphala and its major compounds, namely gallic acid, chebulagic acid, and chebulinic acid, in lung epithelial cells (A549) induced by CoV2-SP. The nanotriphala formulation was prepared using the solvent displacement method. The encapsulation efficiency of Triphala in nanotriphala was determined to be 87.96 ± 2.60% based on total phenolic content. In terms of in vitro release, nanotriphala exhibited a biphasic release profile with zero-order kinetics over 0–8 h. A549 cells were treated with nanotriphala or its active compounds and then induced with 100 ng/mL of spike S1 subunit (CoV2-SP). The results demonstrate that chebulagic acid and chebulinic acid are the active compounds in nanotriphala, which significantly reduced cytokine release (IL-6, IL-1β, and IL-18) and suppressed the expression of inflammatory genes (IL-6, IL-1β, IL-18, and NLRP3) (p < 0.05). Mechanistically, nanotriphala and its active compounds notably attenuated the expression of inflammasome machinery proteins (NLRP3, ASC, and Caspase-1) (p < 0.05). In conclusion, the nanoparticle formulation of Triphala enhances its stability and exhibits anti-inflammatory properties against CoV2-SP-induction. This was achieved by suppressing inflammatory mediators and the NLRP3 inflammasome machinery. Thus, nanotriphala holds promise as a supportive preventive anti-inflammatory therapy for COVID-19-related chronic inflammation.

Objective: Non-small cell lung cancer (NSCLC) is recognized for its aggressive nature and propensity for high rates of metastasis. The NLRP3 inflammasome pathway plays a vital role in the progression of NSCLC. This study aimed to investigate the effects of S. exigua extract and its active compounds on NLRP3 regulation in NSCLC using an in vitro model.Methods:S. exigua was extracted using hexane, ethyl acetate and ethanol to obtain S. exigua hexane fraction (SE-Hex), S. exigua ethyl acetate fraction (SE-EA), and S. exigua ethanol fraction (SE-EtOH) respectively. The active compounds were identified using column chromatography and NMR analysis. A549 cells were primed with lipopolysaccharide (LPS) and adenosine triphosphate (ATP) for activated NLRP3 inflammasome. The anti-inflammatory properties were determined using ELISA assay. The anti-proliferation and anti-metastasis properties against LPS-ATP-induced A549 cells were determined by colony formation, cell cycle, wound healing, and trans-well migration and invasion assays. The inflammatory gene expressions and molecular mechanism were determined using RT-qPCR and Western blot analysis, respectively.Results: SE-EA exhibited the greatest anti-inflammation properties compared with other two fractions as evidenced by the significant inhibition of IL-1β, IL-18, and IL-6, cytokine productions from LPS-ATP-induced A549 cells in a dose-dependent manner (p < 0.05). The analysis of active compounds revealed exiguaflavanone A (EGF-A) and exiguaflavanone B (EGF-B) as the major compounds present in SE-EA. Then, SE-EA and its major compound were investigated for the anti-proliferation and anti-metastasis properties. It was found that SE-EA, EGF-A, and EGF-B could inhibit the proliferation of LPS-ATP-induced A549 cells through cell cycle arrest induction at the G0/G1 phase and reducing the expression of cell cycle regulator proteins. Furthermore, SE-EA and its major compounds dose-dependently suppressed migration and invasion of LPS-ATP-induced A549 cells. At the molecular level, SE-EA, EGF-A, and EGF-B significantly downregulated the mRNA expression of IL-1β, IL-18, IL-6, and NLRP3 in LPS-ATP-induced A549 cells. Regarding the mechanistic study, SE-EA, EGF-A, and EGF-B inhibited NLRP3 inflammasome activation through suppressing NLRP3, ASC, pro-caspase-1(p50 form), and cleaved-caspase-1(p20 form) expressions.Conclusion: Targeting NLRP3 inflammasome pathway holds promise as a therapeutic approach to counteract pro-tumorigenic inflammation and develop novel treatments for NSCLC.

ObjectiveThe multi-systemic inflammation as a result of COVID-19 can persevere long after the initial symptoms of the illness have subsided. These effects are referred to as Long-COVID. Our research focused on the contribution of the Spike protein S1 subunit of SARS-CoV-2 (Spike S1) on the lung inflammation mediated by NLRP3 inflammasome machinery and the cytokine releases, interleukin 6 (IL-6), IL-1beta, and IL-18, in lung epithelial cells. This study has attempted to identify the naturally- occurring agents that act against inflammation-related long-COVID. The seed meal of Perilla frutescens (P. frutescens), which contains two major dietary polyphenols (rosmarinic acid and luteolin), has been reported to exhibit anti-inflammation activities. Therefore, we have established the ethyl acetate fraction of P. frutescens seed meal (PFEA) and determined its anti-inflammatory effects on Spike S1 exposure in A549 lung cells.MethodsPFEA was established using solvent-partitioned extraction. Rosmarinic acid (Ra) and luteolin (Lu) in PFEA were identified using the HPLC technique. The inhibitory effects of PFEA and its active compounds against Spike S1-induced inflammatory response in A549 cells were determined by RT-PCR and ELISA. The mechanistic study of anti-inflammatory properties of PFEA and Lu were determined using western blot technique.ResultsPFEA was found to contain Ra (388.70 ± 11.12 mg/g extract) and Lu (248.82 ± 12.34 mg/g extract) as its major polyphenols. Accordingly, A549 lung cells were pre-treated with PFEA (12.5-100 μg/mL) and its two major compounds (2.5-20 μg/mL) prior to the Spike S1 exposure at 100 ng/mL. PFEA dose-dependently exhibited anti-inflammatory properties upon Spike S1-exposed A549 cells through IL-6, IL-1β, IL-18, and NLRP3 gene suppressions, as well as IL-6, IL-1β, and IL-18 cytokine releases with statistical significance (p < 0.05). Importantly, Lu possesses superior anti-inflammatory properties when compared with Ra (p < 0.01). Mechanistically, PFEA and Lu effectively attenuated a Spike S1-induced inflammatory response through downregulation of the JAK1/STAT3-inflammasome-dependent inflammatory pathway as evidenced by the downregulation of NLRP3, ASC, and cleaved-caspase-1 of the NLRP3 inflammasome components and by modulating the phosphorylation of JAK1 and STAT3 proteins (p < 0.05).ConclusionThe findings suggested that luteolin and PFEA can modulate the signaling cascades that regulate Spike S1-induced lung inflammation during the incidence of Long-COVID. Consequently, luteolin and P. frutescens may be introduced as potential candidates in the preventive therapeutic strategy for inflammation-related post-acute sequelae of COVID-19.

Background:Dugongs are marine mammals with a crescent-shaped tail fluke and a concave trailing margin that belong to the family Dugongidae., They are distributed widely in the warm coastal waters of the Indo-Pacific region. Importantly, the population of dugongs has decreased over the past decades as they have been classified as rare marine mammals. Previous studies have investigated the habitat and genetic diversity of dugongs. However, a comprehensive histological investigation of their tissue has not yet been conducted. This study provides unique insight into the organs of dugongs and compares them with other mammal species.Methods:Tissue sections were stained with Harris's hematoxylin and eosin Y. The histological structure of 17 organ tissues obtained from eight systems was included in this study. Tissue sections were obtained from the urinary system (kidney), muscular system (striated skeletal muscle and smooth muscle), cardiovascular system (cardiac muscle (ventricle), coronary artery, and coronary vein), respiratory system (trachea and lung), gastrointestinal system (esophagus, stomach, small intestine, liver, and pancreas), reproductive system (testis), lymphatic system (spleen and thymus), and endocrine system (pancreas).Results:While most structures were similar to those of other mammal species, there were some differences in the tissue sections of dugongs when compared with other mammalian species and manatees. These include the kidneys of dugongs, which were non-lobular and had a smooth, elongated exterior resulting in a long medullary crest, whereas the dugong pyloric epithelium did not have overlying stratified squamous cells and was noticably different from the Florida manatee.Discussion:Histological information obtained from various organs of the dugong can serve as an essential foundation of basal data for future microanatomical studies. This information can also be used as high-value data in the diagnosis and pathogenesis of sick dugongs or those with an unknown cause of death.

The activation of the NLRP3 inflammasome pathway during infectious pathogen-induced immunopathology can lead to chronic inflammation and various adverse health outcomes. Identification of functional foods with anti-inflammatory properties is crucial for preventing inflammation triggered by NLRP3 inflammasome activation. This study aimed to investigate the anti-inflammatory properties of a proanthocyanidin-rich fraction obtained from red rice germ and bran against lipopolysaccharide (LPS) and adenosine triphosphate (ATP)-induced condition in A549 lung cells. The proanthocyanidin-rich fraction from Yamuechaebia 3 red rice extract (YM3-PRF) was obtained using column chromatography with Sephadex LH20, and its total proanthocyanidin content was determined to be 351.43 ± 1.18 mg/g extract using the vanillin assay. A549 lung cells were pretreated with YM3-PRF at concentrations of 5–20 μg/mL prior to exposure to LPS (1 μg/mL) and ATP (5 nM). The results showed that YM3-PRF significantly inhibited the expression of inflammatory mRNAs (NLRP3, IL-6, IL-1β, and IL-18) and the secretion of cytokines (IL-6, IL-1β, and IL-18) in a dose-dependent manner (p < 0.05). Mechanistically, YM3-PRF exerted its anti-inflammatory effects by inhibiting NF-κB translocation and downregulating proteins associated with the NLRP3 inflammasome pathway (NLRP3, ASC, pro-caspase-1, and cleaved-caspase-1). These findings suggest that the proanthocyanidin-rich fraction from red rice germ and bran has protective effects and may serve as a potential therapeutic option for chronic inflammatory diseases associated with NLRP3 inflammasome activation.

The use of Colistin, a last-resort antimicrobial drug, carries the risk of acute kidney injury. The objective of the study was to assess the effectiveness of colistin-encapsulated liposomes (CL) in reducing nephrotoxicity. Additionally, a liposomal preparation of colistimethate sodium was formulated using the reverse phase evaporation method with a 3:1 ratio of phospholipids to cholesterol. The liposomal properties were evaluated using scanning electron microscopy, photon correlation spectroscopy, and release kinetic assay. The killing kinetics of the formulations on embryonic kidney cells were assessed using in vitro MTT reduction assay. The nephrotoxicity of CL and colistimethate sodium solution (CS) was evaluated in vivo by administering a dose of 20 mg/kg to rats every 12 h for 3 days, with a negative control group receiving a 0.9% saline solution (NSS). The study results revealed that monodisperses of CL showed a smooth surface and distinct boundaries, with an average size of 151.50 ± 0.46 nm and a narrow size distribution of 0.25 ± 0.01. The liposomal particles showed high entrapment efficiency of 96.45% ± 0.41%, with a ζ-potential of −60.80 ± 1.01 mV and a release rate of 50% of colistimethate sodium within the first 480 min. The CL induced nephrocytotoxicity in a concentration- and time-dependent manner. However, CS had notably lower IC50 values compared to its liposome preparations at 48 and 72 h (p < 0.05). In vivo study results show that serum levels of symmetric dimethylarginine (SDMA) and total white blood cell count (WBC) were significantly lower in the CL group (SDMA = 8.33 ± 1.70 μg/dL; WBC = 7.29 ± 0.99 log10 cells/mL) compared to the CS group (SDMA = 15.00 ± 1.63 μg/dL; WBC = 9.73 ± 0.51 log10 cells/mL). Our study findings enhance the understanding of the safety profile of CL and its potential to improve patient outcomes through the use of liposomal colistin medication. Additional clinical studies are necessary to establish the optimal safety regiment in humans.

Black rice has numerous health benefits and one of the well-known functional foods throughout the world. To encourage the increasing trend of the consumer interest in health-promoting functional foods, special varieties of rice have been developed offering greater nutrient values and exhibiting biological activities that are beneficial to the consumer. In this study, we aimed to evaluate the associations of the phytochemical contents, antioxidants, and anti-inflammatory properties among eight selected black rice germ and bran extracts (BR extracts) from 4 non-glutinous and 4 glutinous rice varieties. Accordingly, glutinous BR extracts possessed higher degree of Cyanidin-3-O-glucoside (C3G), Peonidin-3-O-glucoside (P3G) contents, antioxidant and anti-inflammatory properties than the non-glutinous BR extracts. Pearson’s correlation indicated that the amount of C3G in the BR extracts had a strong positive association with the antioxidant properties (DPPH; r = 0.846, ABTS; r = 0.923, and FRAP; r = 0.958, p < 0.01). While P3G exhibited a strong positive association with the anti-inflammatory properties (r value = 0.717 and 0.797 for IL-6 and TNF-α inhibition, respectively, p < 0.05). Lastly, the principal component analysis (PCA) categorized the black rice varieties into three groups: Group A with high C3G content and superior antioxidant properties, Groups B with a high amount of P3G and potent anti-inflammatory properties, and Group C with a lower amount of phytochemical contents and less potent bioactivities. Overall, the outcomes of this study could provide vital information to food industries in selecting the variety of black rice for the functional food based on the anthocyanin contents that could benefit to consumers for new normal healthy lifestyle.

Black rice is a functional food that is high in anthocyanin content, primarily C3G and P3G. It possesses nutraceutical properties that exhibit a range of beneficial effects on human health. Currently, the spike glycoprotein S1 subunit of SARS-CoV-2 (SP) has been reported for its contribution to pathological inflammatory responses in targeting lung tissue and innate immune cells during COVID-19 infection and in the long-COVID phenomenon. Our objectives focused on the health benefits of the C3G and P3G-rich fraction of black rice germ and bran (BR extract) on the inhibition of inflammatory responses induced by SP, as well as the inhibition of NF-kB activation and the NLRP3 inflammasome pathway in an in vitro model. In this study, BR extract was identified for its active anthocyanins, C3G and P3G, using the HPLC technique. A549-lung cells and differentiated THP-1 macrophages were treated with BR extract, C3G, or P3G prior to exposure to 100 ng/mL of SP. Their anti-inflammatory properties were then determined. BR extract at concentrations of 12.5–100 μg/mL exhibited anti-inflammation activity for both A549 and THP-1 cells through the significant suppression of NLRP3, IL-1β, and IL-18 inflammatory gene expressions and IL-6, IL-1β, and IL-18 cytokine secretions in a dose-dependent manner (p < 0.05). It was determined that both cell lines, C3G and P3G (at 1.25–10 μg/mL), were compatibly responsible for the significant inhibition of SP-induced inflammatory responses for both gene and protein levels (p < 0.05). With regard to the anti-inflammation mechanism, BR extract, C3G, and P3G could attenuate SP-induced inflammation via counteraction with NF-kB activation and downregulation of the inflammasome-dependent inflammatory pathway proteins (NLRP3, ASC, and capase-1). Overall, the protective effects of anthocyanins obtained from black rice germ and bran can be employed in potentially preventive strategies that use pigmented rice against the long-term sequelae of COVID-19 infection.

Inhibition of inflammatory responses from the spike glycoprotein of SARS-CoV-2 (Spike) by targeting NLRP3 inflammasome has recently been developed as an alternative form of supportive therapy besides the traditional anti-viral approaches. Clerodendrum petasites S. Moore (C. petasites) is a Thai traditional medicinal plant possessing antipyretic and anti-inflammatory activities. In this study, C. petasites ethanolic root extract (CpEE) underwent solvent-partitioned extraction to obtain the ethyl acetate fraction of C. petasites (CpEA). Subsequently, C. petasites extracts were determined for the flavonoid contents and anti-inflammatory properties against spike induction in the A549 lung cells. According to the HPLC results, CpEA significantly contained higher amounts of hesperidin and hesperetin flavonoids than CpEE (p < 0.05). A549 cells were then pre-treated with either C. petasites extracts or its active flavonoids and were primed with 100 ng/mL of spike S1 subunit (Spike S1) and determined for the anti-inflammatory properties. The results indicate that CpEA (compared with CpEE) and hesperetin (compared with hesperidin) exhibited greater anti-inflammatory properties upon Spike S1 induction through a significant reduction in IL-6, IL-1β, and IL-18 cytokine releases in A549 cells culture supernatant (p < 0.05). Additionally, CpEA and hesperetin significantly inhibited the Spike S1-induced inflammatory gene expressions (NLRP3, IL-1β, and IL-18, p < 0.05). Mechanistically, CpEA and hesperetin attenuated inflammasome machinery protein expressions (NLRP3, ASC, and Caspase-1), as well as inactivated the Akt/MAPK/AP-1 pathway. Overall, our findings could provide scientific-based evidence to support the use of C. petasites and hesperetin in the development of supportive therapies for the prevention of COVID-19-related chronic inflammation.

Recently, the global trend toward the use of natural extracts and antioxidant agents in the cosmetic cream industry to produce whitening effects has been increasing. This has also been a persistent trend in Thailand. In this study, samples of commercial cosmetic creams on the Thai market were assessed for a functional evaluation of their antioxidant activity, tyrosinase inhibitory effects, and phenolic contents. Samples were extracted using hot water and sonication extraction method to obtain the functional cream extracts. Total phenolic contents in all samples were within the range of 0.46–47.92 mg GAE/30 g cream. Antioxidant activities of the cream extracts were within the range of 3.61–43.98 mg Trolox equivalent/30 g cream, while tyrosinase inhibition activities were within the range of 2.58–97.94% of inhibition. With regard to the relationship between the total phenolic content and the antioxidant activity of the cosmetic creams, Pearson’s correlation coefficient revealed a moderately positive relationship with an r value of 0.6108. Furthermore, the relationship between the antioxidant activity and the tyrosinase inhibitory activity of the cosmetic creams was highly positive with an r value of 0.7238. Overall, this study demonstrated that the total phenolic contents in the functional cosmetic creams could play a role in antioxidant activity and anti-tyrosinase activities. The findings indicate how the whitening and antioxidant effects of cosmetic creams could be maintained after the products have been formulated, as this concern can affect the consumer’s decision when purchasing cosmetic products.

Auricularia auricula-judae, a nutrient-rich mushroom used in traditional medicine, is a macrofungi that exhibits various biological properties. In this study, we have reported on the mechanisms that promote the wound-healing effects of a water-soluble polysaccharide-rich extract obtained from A. auricula-judae (AAP). AAP contained high amounts of polysaccharides (349.83 ± 5.00 mg/g extract) with a molecular weight of 158 kDa. The main sugar composition of AAP includes mannose, galactose, and glucose. AAP displayed antioxidant activity in vitro and was able to abort UVB-induced intracellular ROS production in human fibroblasts in cellulo. AAP significantly promoted both fibroblast and keratinocyte proliferation, migration, and invasion, along with augmentation of the wound-healing process by increasing collagen synthesis and decreasing E-cadherin expression (All p < 0.05). Specifically, the AAP significantly accelerated the wound closure in a mice skin wound-healing model on day 9 (2.5%AAP, p = 0.031 vs. control) and day 12 (1% and 2.5%AAP with p = 0.009 and p < 0.001 vs. control, respectively). Overall, our results indicate that the wound-healing activities of AAP can be applied in an AAP-based product for wound management.