Orally Ingested Self-Powered Stimulators for Targeted Gut-Brain Axis Electrostimulation to Treat Obesity and Metabolic Disorders.

Obesity is a significant health concern that often leads to metabolic dysfunction and chronic diseases. This study introduces a novel approach to combat obesity using orally ingested self-powered electrostimulators. These electrostimulators consist of piezoelectric BaTiO3 (BTO) particles conjugated with capsaicin (Cap) and aim to activate the vagus nerve. Upon ingestion by diet-induced obese (DIO) mice, the BTO@Cap particles specifically target and bind to Cap-sensitive sensory nerve endings in the gastric mucosa. In response to stomach peristalsis, these particles generate electrical signals. The signals travel via the gut-brain axis, ultimately influencing the hypothalamus. By enhancing satiety signals in the brain, this neuromodulatory intervention reduces food intake, promotes energy metabolism, and demonstrates minimal toxicity. Over a 3-week period of daily treatments, DIO mice treated with BTO@Cap particles show a significant reduction in body weight compared to control mice, while maintaining their general locomotor activity. Furthermore, this BTO@Cap particle-based treatment mitigates various metabolic alterations associated with obesity. Importantly, this noninvasive and easy-to-administer intervention holds potential for addressing other intracerebral neurological diseases.

Seven new triterpenoids from the roots of Adenophora tetraphylla (Thub.) Fisch.

Seven new triterpenoids, named Adeterpenoids A-G (1-7) and eight known compounds (8-15), were isolated from 70% ethanol extract of the roots of Adenophora tetraphylla (Thub.) Fisch. The compounds from it were separated by column chromatography techniques such as silica gel, ODS, and preparative liquid chromatography. Their structures were clarified based on extensive spectral analysis (1D, 2D-NMR, HR-ESI-MS, IR, UV, and CD) and comparison with the literature. At the same time, all compounds were evaluated for their cytotoxic activity against the LN229 (human glioma cell line). The results showed that compounds 2, 5, 6, 13, and 14 had a significant inhibitory effect on LN229 cells.

Effectiveness of Electroencephalography Neurofeedback for Improving Working Memory and Episodic Memory in the Elderly: A Meta-Analysis.

Background and Objective: Existing evidence indicates the potential benefits of electroencephalography neurofeedback (NFB) training for cognitive function. This study aims to comprehensively review all available evidence investigating the effectiveness of NFB on working memory (WM) and episodic memory (EM) in the elderly population. Material and Methods: A systematic search was conducted across five databases to identify clinical trials examining the impact of NFB on memory function in healthy elderly individuals or those with mild cognitive impairment (MCI). The co-primary outcomes focused on changes in WM and EM. Data synthesis was performed using a random-effects meta-analysis. Results: Fourteen clinical trials (n = 284) were included in the analysis. The findings revealed that NFB was associated with improved WM (k = 11, reported as Hedges' g = 0.665, 95% confidence [CI] = 0.473 to 0.858, p < 0.001) and EM (k = 12, 0.595, 0.333 to 0.856, p < 0.001) in the elderly, with moderate effect sizes. Subgroup analyses demonstrated that NFB had a positive impact on both WM and EM, not only in the healthy population (WM: k = 7, 0.495, 0.213 to 0.778, p = 0.001; EM: k = 6, 0.729, 0.483 to 0.976, p < 0.001) but also in those with MCI (WM: k = 6, 0.812, 0.549 to 1.074, p < 0.001; EM: k = 6, 0.503, 0.088 to 0.919, p = 0.018). Additionally, sufficient training time (totaling more than 300 min) was associated with a significant improvement in WM (k = 6, 0.743, 0.510 to 0.976, p < 0.001) and EM (k = 7, 0.516, 0.156 to 0.876, p = 0.005); however, such benefits were not observed in groups with inadequate training time. Conclusions: The results suggest that NFB is associated with enhancement of both WM and EM in both healthy and MCI elderly individuals, particularly when adequate training time (exceeding 300 min) is provided. These findings underscore the potential of NFB in dementia prevention or rehabilitation.

Fabrication of Microalgae Oil Vesicles for Drug Delivery Applications.

In this study, it is demonstrated that natural microalgae oils, which contain fatty acid components including docosahexaenoic acid (DHA), could be directly applied to fabricate vesicular structures in aqueous phase through a forced formation process. The microalgae oil vesicles had initial average diameters of 170- 230 nm with negative charges apparently caused by dissociation of the fatty acid components. The vesicles possessed excellent stability with lifetimes for at least 450 days. The formation of the vesicular structures with hydrophilic cores/regions was confirmed by the transmission electron microscopy (TEM) image and successful encapsulation of a hydrophilic material. For encapsulation of a hydrophobic material, lutein, the vesicle size was increased probably due to the insertion of lutein into the hydrophobic vesicular bilayer structures. The analysis of Fourier transform infrared (FTIR) spectroscopy suggested that the vesicular bilayer fluidity was decreased by encapsulating lutein. However, the lutein-encapsulating microalgae oil vesicles still possessed high stability and the vesicular structures could maintain intact even at an environmental temperature up to 60℃. Applicability of the microalgae oil vesicles as drug delivery carriers was also demonstrated by successful encapsulation of curcumin. However, when the loaded curcumin was increased to a certain amount, physical stability of the microalgae oil vesicles was significantly reduced. This is probably because the vesicular structures with only limited spaces for accommodating hydrophobic materials were strongly affected by encapsulating a large amount of curcumin. It is interesting to note that by adding egg L-α-phosphatidylcholine, the curcumin encapsulation-induced instability of the microalgae oil vesicles could be alleviated. The results indicated that vesicular structures could be fabricated from microalgae oils and the microalgae oil vesicles were capable of encapsulating hydrophilic or hydrophobic materials for drug delivery applications. The findings lay a background for further dosage form development of nutritional supplements encapsulated by natural microalgae oils.

Identification of anti-fibrotic and pro-apoptotic bioactive compounds from Ganoderma formosanum and their possible mechanisms in modulating TGF-ß1-induced lung fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: The Compendium of Materia Medica and the Classic of Materia Medica, the two most prominent records of traditional Chinese medicine, documented the therapeutic benefits of Ganoderma sinense particularly in addressing pulmonary-related ailments. Ganoderma formosanum, an indigenous subspecies of G. sinense from Taiwan, has demonstrated the same therapeutic properties. AIM OF THE STUDY: The aim of this study is to identify bioactive compounds and evaluate the potential of G. formosanum extracts as a novel treatment to alleviate pulmonary fibrosis (PF). Using an in-house drug screening platform, two-stage screening was performed to determine their anti-fibrotic efficacy. METHODS AND MATERIALS: G. formosanum was fractionated into four partitions by solvents of different polarities. To determine their antifibrotic and pro-apoptotic properties, the fractions were analyzed using two TGF-ß1-induced pulmonary fibrosis cell models (NIH-3T3) and human pulmonary fibroblast cell lines, immunoblot, qRT-PCR, and annexin V assays. Subsequently, transcriptomic analysis was conducted to validate the findings and explore possible molecular pathways. The identification of potential bioactive compounds was achieved through UHPLC-MS/MS analysis, while molecular interaction study was investigated by multiple ligands docking and molecular dynamic simulations. RESULTS: The ethyl acetate fraction (EAF) extracted from G. formosanum demonstrated substantial anti-fibrotic and pro-apoptotic effects on TGF-ß1-induced fibrotic models. Moreover, the EAF exhibited no discernible cytotoxicity. Untargeted UHPLC-MS/MS analysis identified potential bioactive compounds in EAF, including stearic acid, palmitic acid, and pentadecanoic acid. Multiple ligands docking and molecular dynamic simulations further confirmed that those bioactive compounds possess the ability to inhibit TGF-ß receptor 1. CONCLUSION: Potential bioactive compounds in G. formosanum were successfully extracted and identified in the EAF, whose anti-fibrotic and pro-apoptotic properties could potentially modulate pulmonary fibrosis. This finding not only highlights the EAF's potential as a promising therapeutic candidate to treat pulmonary fibrosis, but it also elucidates how Ganoderma confers pulmonary health benefits as described in the ancient texts.

Risk of Excess Maternal Folic Acid Supplementation in Offspring.

Folate, also known as vitamin B9, facilitates the transfer of methyl groups among molecules, which is crucial for amino acid metabolism and nucleotide synthesis. Adequate maternal folate supplementation has been widely acknowledged for its pivotal role in promoting cell proliferation and preventing neural tube defects. However, in the post-fortification era, there has been a rising concern regarding an excess maternal intake of folic acid (FA), the synthetic form of folate. In this review, we focused on recent advancements in understanding the influence of excess maternal FA intake on offspring. For human studies, we summarized findings from clinical trials investigating the effects of periconceptional FA intake on neurodevelopment and molecular-level changes in offspring. For studies using mouse models, we compiled the impact of high maternal FA supplementation on gene expression and behavioral changes in offspring. In summary, excessive maternal folate intake could potentially have adverse effects on offspring. Overall, we highlighted concerns regarding elevated maternal folate status in the population, providing a comprehensive perspective on the potential adverse effects of excessive maternal FA supplementation on offspring.

Inorganic nanoparticles for photothermal treatment of cancer.

In recent years, inorganic nanoparticles (NPs) have attracted increasing attention as potential theranostic agents in the field of oncology. Photothermal therapy (PTT) is a minimally invasive technique that uses nanoparticles to produce heat from light to kill cancer cells. PTT requires two essential elements: a photothermal agent (PTA) and near-infrared (NIR) radiation. The role of PTAs is to absorb NIR, which subsequently triggers hyperthermia within cancer cells. By raising the temperature in the tumor microenvironment (TME), PTT causes damage to the cancer cells. Nanoparticles (NPs) are instrumental in PTT given that they facilitate the passive and active targeting of the PTA to the TME, making them crucial for the effectiveness of the treatment. In addition, specific targeting can be achieved through their enhanced permeation and retention effect. Thus, owing to their significant advantages, such as altering the morphology and surface characteristics of nanocarriers comprised of PTA, NPs have been exploited to facilitate tumor regression significantly. This review highlights the properties of PTAs, the mechanism of PTT, and the results obtained from the improved curative efficacy of PTT by utilizing NPs platforms.

Trace element levels in the muscles of three tern species (Aves: Laridae) from the western Arabian Gulf: environmental assessment and implications for conservation.

In the Arabian Gulf (called also Persian Gulf; hereafter 'the Gulf'), Jana and Karan Islands are recognized as one of the most Important Bird Areas in the region. Many migratory breeding seabirds, like the Greater Crested Tern Thalasseus bergii, White-cheeked Tern Sterna repressa and Bridled Tern Onychoprion anaethetus, depend on these islands during the breeding season. However, these aquatic wildlife species are suffering from intensified urban and industrial coastal development and various contamination events including wars and related oil spills. In this study, we used these three piscivorous top predator birds to analyse the levels of 19 trace elements (TEs; i.e. Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, Hg, K, Mg, Mn, Na, Ni, Pb, Sr, V and Zn) in 15 muscular tissue samples from Jana and Karan Islands. PERMANOVA analysis showed no difference in contamination profile between sites nor between species probably due to their spatial and ecological proximity and therefore similar levels of exposure to TEs. Comparing these levels with existing literature, our results showed no particular concern for all elements, except for Al (maximum values recorded = 116.5 µg g-1 d.w.) and, in two samples, Ba (33.67 µg g-1 d.w.) and Pb (5.6 µg g-1 d.w.). The results can be considered as an initial step for supplementary evaluations with a larger number of samples and specified time intervals for the collection of specimens. This study provided baseline information on the pollution status of these two ecologically important sites which require a continuous biomonitoring programme.

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

A prospective review of the health-promoting potential of Jing Si Herbal Tea.

Traditional Chinese medicine (TCM) has gained considerable attention over the past few years for its multicomponent, multitarget, and multi-pathway approach to treating different diseases. Studies have shown that TCMs as adjuvant therapy along with conventional treatment may benefit in safely treating various disorders. However, investigations on finding effective herbal combinations are ongoing. A novel TCM formula, "Jing Si Herbal Tea (JSHT)," has been reported recently for their health-promoting effects in improving overall body and mental health. JSHT is a combination of eight herbs recognized in Chinese herbal pharmacopoeia for their anti-viral, anti-aging, and anti-cancer properties as well as protective effects against cardiovascular, metabolic, neural, digestive, and genitourinary diseases. Thus, to better understand the beneficial effects of the ingredients of JSHT on health, this review intends to summarize the preclinical and clinical studies of the ingredients of JSHT on human health and diseases, and possible therapeutic effects with the related mode of actions and future prospects for their application in complementary therapies.

Effects of dietary Nisin on growth performance, immune function, and gut health of broilers challenged by Clostridium perfringens.

Nisin (Ni) is a polypeptide bacteriocin produced by lactic streptococci (probiotics) that can inhibit the majority of gram-positive bacteria, and improve the growth performance of broilers, and exert antioxidative and anti-inflammatory properties. The present study investigated the potential preventive effect of Nisin on necrotic enteritis induced by Clostridium perfringens (Cp) challenge. A total of 288 Arbor Acres broiler chickens of 1-d-olds were allocated using 2 × 2 factorial arrangement into four groups with six replicates (12 chickens per replicate), including: (1) control group (Con, basal diet), (2) Cp challenge group (Cp, basal diet + 1.0 × 108 CFU/mL Cp), (3) Ni group (Ni, basal diet + 100 mg/kg Ni), and (4) Ni + Cp group (Ni + Cp, basal diet + 100 mg/kg Ni + 1.0 × 108 CFU/mL Cp). The results showed that Cp challenge decreased the average daily gain (ADG) of days 15 to 21 (P<0.05) and increased interleukin-6 (IL-6) content in the serum (P < 0.05), as well as a significant reduction in villus height (VH) and the ratio of VH to crypt depth (VCR) (P<0.05) and a significant increase in crypt depth (CD) of jejunum (P<0.05). Furthermore, the mRNA expressions of Occludin and Claudin-1 were downregulated (P<0.05), while the mRNA expressions of Caspase3, Caspase9, Bax, and Bax/Bcl-2 were upregulated (P<0.05) in the jejunum. However, the inclusion of dietary Ni supplementation significantly improved body weight (BW) on days 21 and 28, ADG of days 15 to 21 (P<0.05), decreased CD in the jejunum, and reduced tumor necrosis factor-α (TNF-α) content in the serum (P<0.05). Ni addition upregulated the mRNA levels of Claudin-1 expression and downregulated the mRNA expression levels of Caspase9 in the jejunum (P<0.05). Moreover, Cp challenge and Ni altered the cecal microbiota composition, which manifested that Cp challenge decreased the relative abundance of phylum Fusobacteriota and increased Shannon index (P<0.05) and the trend of phylum Proteobacteria (0.05

Necrotic enteritis (NE), a severe digestive disorder in broiler chickens caused by Clostridium perfringens (Cp), a gram-positive bacterium, is a widespread issue in the global poultry industry, leading to significant economic losses. Nisin (Ni), a polypeptide bacteriocin produced by probiotic lactic streptococci, has been found to enhance daily weight gain and feed intake, while also exhibiting inhibitory effects on gram-positive bacteria and anti-inflammatory properties. In this study, a NE infection model in broilers was established to examine the potential preventive effects of Ni. These results demonstrated that Cp challenge reduced growth performance, caused inflammatory responses and intestinal apoptosis, damaged intestinal morphology and barrier function, and was accompanied by changes in the composition of the gut microbiota. Dietary supplementation with Ni improved growth performance and protected intestine against Cp challenge-induced damage in broilers. As a result, Ni may be a potential safe and effective additive for NE prevention in broiler production.

Injectable, Antioxidative, and Tissue-Adhesive Nanocomposite Hydrogel as a Potential Treatment for Inner Retina Injuries.

Reactive oxygen species (ROS) have been recognized as prevalent contributors to the development of inner retinal injuries including optic neuropathies such as glaucoma, non-arteritic anterior ischemic optic neuropathy, traumatic optic neuropathy, and Leber hereditary optic neuropathy, among others. This underscores the pivotal significance of oxidative stress in the damage inflicted upon retinal tissue. To combat ROS-related challenges, this study focuses on creating an injectable and tissue-adhesive hydrogel with tailored antioxidant properties for retinal applications. GelCA, a gelatin-modified hydrogel with photo-crosslinkable and injectable properties, is developed. To enhance its antioxidant capabilities, curcumin-loaded polydopamine nanoparticles (Cur@PDA NPs) are incorporated into the GelCA matrix, resulting in a multifunctional nanocomposite hydrogel referred to as Cur@PDA@GelCA. This hydrogel exhibits excellent biocompatibility in both in vitro and in vivo assessments, along with enhanced tissue adhesion facilitated by NPs in an in vivo model. Importantly, Cur@PDA@GelCA demonstrates the potential to mitigate oxidative stress when administered via intravitreal injection in retinal injury models such as the optic nerve crush model. These findings underscore its promise in advancing retinal tissue engineering and providing an innovative strategy for acute neuroprotection in the context of inner retinal injuries.

Plant-derived galactolipids enhance specific antibody production and induce class-switch as vaccine adjuvant.

Various plant-derived compounds can activate immune responses against bacterial infections, and this property contributes to them being developed as effective and safe adjuvants for vaccines. This study evaluated the potential adjuvant effects of a galactolipid-enriched fraction generated from the medicinal plant Crassocephalum rabens (designated CRA). Heat shock protein 60 of periodontal disease pathogen Actinobacillus actinomycetemcomitans (AaHSP60) was taken as an antigen and mixed with CRA. The AaHSP60/CRA mixture was then injected intraperitoneally into the BALB/c mice. Titers and affinity of specific antibodies were measured by ELISA. Cytokine profiles in mouse serum or culture media of AaHSP60/CRA-treated splenocytes were analyzed by cytokine multiplex assay and ELISA kits. B cell differentiation and macrophage activation were determined by phenotyping. CRA dramatically enhanced specific antibody titers and induced Ig class switch, as shown by increases in the IgG2a, IgG2b, and IgG3 proportions of total Ig in mouse serum. Furthermore, CRA-induced anti-AaHSP60 antibodies had cross-reactivity to other bacterial HSP60s. Cell-based and animal results demonstrated that CRA induced the release of IL-21 and B cell activating factor (BAFF), which stimulated B cell differentiation. CRA enhanced cell proliferation, uptake ability, and antigen presentation in mouse phagocytes. CRA served as a vaccine adjuvant that enhance mouse immunity against pathogenic antigens. CRA strengthened the activation and capabilities of phagocytes and B cells. Therefore, CRA may be a promising adjuvant for bacterial vaccines including periodontal disease.

Inhibition of Polyinosinic-Polycytidylic Acid-Induced Acute Pulmonary Inflammation and NF-κB Activation in Mice by a Banana Plant Extract.

NF-κB activation is pivotal for the excess inflammation causing the critical condition and mortality of respiratory viral infection patients. This study was aimed to evaluate the effect of a banana plant extract (BPE) on suppressing NF-κB activity and acute lung inflammatory responses in mice induced by a synthetic double-stranded RNA viral mimetic, polyinosinic-polycytidylic acid (poly (I:C)). The inflammatory responses were analyzed by immunohistochemistry and HE stains and ELISA. The NF-κB activities were detected by immunohistochemistry in vivo and immunofluorescence and Western blot in vitro. Results showed that BPE significantly decreased influx of immune cells (neutrophils, lymphocytes, and total WBC), markedly suppressed the elevation of pro-inflammatory cytokines and chemokines (IL-6, RANTES, IFN-γ, MCP-1, keratinocyte-derived chemokine, and IL-17), and restored the diminished anti-inflammatory IL-10 in the bronchoalveolar lavage fluid (BALF) of poly (I:C)-stimulated mice. Accordingly, HE staining revealed that BPE treatment alleviated poly (I:C)-induced inflammatory cell infiltration and histopathologic changes in mice lungs. Moreover, immunohistochemical analysis showed that BPE reduced the pulmonary IL-6, CD11b (macrophage marker), and nuclear NF-κB p65 staining intensities, whilst restored that of IL-10 in poly (I:C)-stimulated mice. In vitro, BPE antagonized poly(I:C)-induced elevation of IL-6, nitric oxide, reactive oxygen species, NF-κB p65 signaling, and transient activation of p38 MAPK in human lung epithelial-like A549 cells. Taken together, BPE ameliorated viral mimic poly(I:C)-induced acute pulmonary inflammation in mice, evidenced by reduced inflammatory cell infiltration and regulation of both pro- and anti-inflammatory cytokines. The mechanism of action might closely associate with NF-κB signaling inhibition.

Photoacoustic Imaging Endometriosis Lesions with Nanoparticulate Polydopamine as a Contrast Agent.

Endometriosis (EM) is a prevalent and debilitating gynecological disorder primarily affecting women of reproductive age. The diagnosis of EM is historically hampered by delays, owing to the absence of reliable diagnostic and monitoring techniques. Herein, it is reported that photoacoustic imaging can be a noninvasive modality for deep-seated EM by employing a hyaluronic-acid-modified polydopamine (PDA@HA) nanoparticle as the contrast agent. The PDA@HA nanoparticles exhibit inherent absorption and photothermal effects when exposed to near-infrared light, proficiently converting thermal energy into sound waves. Leveraging the targeting properties of HA, distinct photoacoustic signals emanating from the periphery of orthotopic EM lesions are observed. These findings are corroborated through anatomical observations and in vivo experiments involving mice with green fluorescent protein-labeled EM lesions. Moreover, the changes in photoacoustic intensity over a 24 h period reflect the dynamic evolution of PDA@HA nanoparticle biodistribution. Through the utilization of a photoacoustic ultrasound modality, in vivo assessments of EM lesion volumes are conducted. This innovative approach not only facilitates real-time monitoring of the therapeutic kinetics of candidate drugs but also obviates the need for the sacrifice of experimental mice. As such, this study presents a promising avenue for enhancing the diagnosis and drug-screening processes of EM.

Licochalcone A regulates viral IRES activity to inhibit enterovirus replication.

Enterovirus D68 (EV-D68), belonging to the genus Enterovirus of the Picornavirus family, is an emerging pathogen that can cause neurological and respiratory diseases in children. However, there is little understanding of the pathogenesis of EV-D68, and no effective vaccine or drug for the prevention or treatment of the diseases caused by this virus is available. Autophagy is a cellular process that targets cytoplasmic proteins or organelles to the lysosomes for degradation. Enteroviruses strategically harness the host autophagy pathway to facilitate the completion of their life cycle. Therefore, we selected an autophagy compound library to screen for autophagy-related compounds that may affect viral growth. By using the neutralization screening assay, we identified a compound, 'licochalcone A' that significantly inhibited EV-D68 replication. To investigate the mechanism by which licochalcone A inhibits EV-D68 replication and to identify the viral life cycle stage it inhibits, the time-of-addition, viral attachment, viral entry, and dual-luciferase reporter assays were performed. The results of the time-of-addition assay showed that licochalcone A, a characteristic chalcone found in liquorice roots and widely used in traditional Chinese medicine, inhibits EV-D68 replication during the early stages of the viral life cycle, while those of the dual-luciferase reporter assay showed that licochalcone A does not regulate viral attachment and entry, but inhibits EV-D68 IRES-dependent translation. Licochalcone A also inhibited enterovirus A71 and coxsackievirus B3 but did not significantly inhibit dengue virus 2 or human coronavirus 229E replication. Licochalcone A regulates IRES translation to inhibit EV-D68 viral replication.

Synergistic effect of photothermal and magnetic hyperthermia for in situ activation of Fenton reaction in tumor microenvironment for chemodynamic therapy.

Traditional cancer treatments are ineffective and cause severe adverse effects. Thus, the development of chemodynamic therapy (CDT) has the potential for in situ catalysis of endogenous molecules into highly toxic species, which would then effectively destroy cancer cells. However, the shortage of high-performance nanomaterials hinders the broad clinical application of this approach. In present study, an effective therapeutic platform was developed using a simple hydrothermal method for the in-situ activation of the Fenton reaction within the tumor microenvironment (TME) to generate substantial quantities of •OH and ultimately destroy cancer cells, which could be further synergistically increased by photothermal therapy (PHT) and magnetic hyperthermia (MHT) aided by FeMoO4 nanorods (NRs). The produced FeMoO4 NRs were used as MHT/PHT and Fenton catalysts. The photothermal conversion efficiency of the FeMoO4 NRs was 31.75 %. In vitro and \ experiments demonstrated that the synergistic combination of MHT/PHT/CDT notably improved anticancer efficacy. This work reveals the significant efficacy of CDT aided by both photothermal and magnetic hyperthermia and offers a feasible strategy for the use of iron-based nanoparticles in the field of biomedical applications.

In Vitro and In Vivo Anti-Cancer Activity of Lasiokaurin in a Triple-Negative Breast Cancer Model.

Due to its intricate heterogeneity, high invasiveness, and poor prognosis, triple-negative breast cancer (TNBC) stands out as the most formidable subtype of breast cancer. At present, chemotherapy remains the prevailing treatment modality for TNBC, primarily due to its lack of estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth receptor 2 (HER2). However, clinical chemotherapy for TNBC is marked by its limited efficacy and a pronounced incidence of adverse effects. Consequently, there is a pressing need for novel drugs to treat TNBC. Given the rich repository of diverse natural compounds in traditional Chinese medicine, identifying potential anti-TNBC agents is a viable strategy. This study investigated lasiokaurin (LAS), a natural diterpenoid abundantly present in Isodon plants, revealing its significant anti-TNBC activity both in vitro and in vivo. Notably, LAS treatment induced cell cycle arrest, apoptosis, and DNA damage in TNBC cells, while concurrently inhibiting cell metastasis. In addition, LAS effectively inhibited the activation of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway and signal transducer and activator of transcription 3 (STAT3), thus establishing its potential for multitarget therapy against TNBC. Furthermore, LAS demonstrated its ability to reduce tumor growth in a xenograft mouse model without exerting detrimental effects on the body weight or vital organs, confirming its safe applicability for TNBC treatment. Overall, this study shows that LAS is a potent candidate for treating TNBC.

Smith-Magenis syndrome protein RAI1 regulates body weight homeostasis through hypothalamic BDNF-producing neurons and neurotrophin downstream signalling.

Retinoic acid-induced 1 (RAI1) haploinsufficiency causes Smith-Magenis syndrome (SMS), a genetic disorder with symptoms including hyperphagia, hyperlipidemia, severe obesity, and autism phenotypes. RAI1 is a transcriptional regulator with a pan-neural expression pattern and hundreds of downstream targets. The mechanisms linking neural Rai1 to body weight regulation remain unclear. Here we find that hypothalamic brain-derived neurotrophic factor (BDNF) and its downstream signalling are disrupted in SMS (Rai1+/-) mice. Selective Rai1 loss from all BDNF-producing cells or from BDNF-producing neurons in the paraventricular nucleus of the hypothalamus (PVH) induced obesity in mice. Electrophysiological recordings revealed that Rai1 ablation decreased the intrinsic excitability of PVHBDNF neurons. Chronic treatment of SMS mice with LM22A-4 engages neurotrophin downstream signalling and delayed obesity onset. This treatment also partially rescued disrupted lipid profiles, insulin intolerance, and stereotypical repetitive behaviour in SMS mice. These data argue that RAI1 regulates body weight and metabolic function through hypothalamic BDNF-producing neurons and that targeting neurotrophin downstream signalling might improve associated SMS phenotypes.