Efficacy of a novel multi-enzyme feed additive on growth performance, nutrient digestibility, and gut microbiome of weanling pigs fed corn-wheat or wheat-barley-based diet.

One-hundred-and-ninety-two weanling pigs (6.7 kg body weight) were used to evaluate the impact of a carbohydrases-protease enzyme complex (CPEC) on growth performance, nutrient digestibility, and gut microbiome. Pigs were assigned to one of the four dietary treatments for 42 d according to a 2 × 2 factorial arrangement of diet type (low fiber [LF] or high fiber [HF]) and CPEC supplementation (0 or 170 mg/kg diet). The LF diet was prepared as corn-wheat-based diet while the HF diet was wheat-barley-based and contained wheat middlings and canola meal. Each dietary treatment consisted of 12 replicate pens (six replicates per gender) and four pigs per replicate pen. Over the 42-d period, there was no interaction between diet type and CPEC supplementation on growth performance indices of pigs. Dietary addition of CPEC improved (P < 0.05) the body weight of pigs at days 28 and 42 and the gain-to-feed ratio of pigs from days 0 to 14. During the entire experimental period, dietary CPEC supplementation improved (P < 0.05) the average daily gain and gain-to-feed ratio of pigs. There were interactions between diet type and CPEC supplementation on apparent total tract digestibility (ATTD) of dry matter (DM; P < 0.01), gross energy (GE; P < 0.01), and neutral detergent fiber (NDF; P < 0.05) at d 42. Dietary CPEC addition improved (P < 0.05) ATTD of DM, GE, and NDF in the HF diets. At day 43, dietary CPEC addition resulted in improved (P < 0.05) apparent ileal digestibility (AID) of NDF and interactions (P < 0.05) between diet type and CPEC supplementation on AID of DM and crude fiber. Alpha diversity indices including phylogenetic diversity and observed amplicon sequence variants of fecal microbiome increased (P < 0.05) by the addition of CPEC to the HF diets on day 42. An interaction (P < 0.05) between diet type and CPEC addition on Bray-Curtis dissimilarity index and Unweighted UniFrac distances was observed on day 42. In conclusion, CPEC improved weanling pig performance and feed efficiency, especially in wheat-barley diets, while dietary fiber composition had a more significant impact on fecal microbial communities than CPEC administration. The results of this study underscores carbohydrase's potential to boost pig performance without major microbiome changes.

There is a pressing need to enhance livestock production efficiency to meet the growing global demand for meat. Carbohydrases and proteases are enzymes typically added to swine diets to improve nutrient utilization, leading to better growth rates and feed efficiency. This ultimately contributes to sustainable and economically viable pig farming. However, more research is required to better understand how carbohydrases and proteases interact with different diet types to optimize dietary formulations, and how this may influence gut microbiome composition. In this study, 192 weaner pigs (~7 kg) were assigned to a low-fiber diet or a high-fiber diet. Each diet type was with or without a carbohydrases and protease multi-enzyme supplementation. The results showed that adding a multi-enzyme combination to the pigs' diet significantly improved the pig's performance, regardless of diet type. Improvement in nutrient digestibility was more pronounced in pigs fed the high-fiber diet and that dietary fiber had a greater influence on the composition of fecal microbes. In essence, the study demonstrates that the multi-enzyme can boost pig growth and feed efficiency in diets with varying fiber complexity without causing significant changes in their gut microbiome.

Nanographene-Au fine-tuning to intensify plasmonic-resonance of polymeric hybrid bionanosystem for synergistic phototherapy and nerve photobiomodulation.

Here, we report the multi-photo-bioactivity of the plasmonic-nano graphitic coordinated polycaprolactone-based aligned nanofibrous scaffolds-based bionanosystem for photothermal breast and colon cancer therapies and peripheral nerve photobiomodulation. The size-optimized colloidal reduced graphene oxide (nRGO, 180 nm) nanosheets, for enhanced photothermal impact, were surface-functionalized with gold nanospheres (AuNPs) to prepare the nRGO@AuNP monodispersed nano-composite and then doped 2.0 mg of nRGO@AuNP in biocompatible and biodegradable polymer polycaprolactone (PCL) to fabricate the nRGO@AuNP-PCL (2.0 mg) plasmonic aligned nanofibrous scaffolds. More than 90% of cancer cells, breast cancer (MCF-7) as well as colon cancer (CT-26), ablated after 5 min of low NIR (808 nm) laser power (0.72 W/cm2) illumination with nRGO@AuNP-PCL (2.0 mg) aligned nanofibrous scaffolds. Besides, the nRGO@AuNP-PCL (2.0 mg) provided an extraordinary microenvironment for adhesion, nerve growth, proliferation, and differentiation of PC12 and S42 cells which mimics the natural extracellular matrix. The 2.5-fold increase in neurite length was observed with NIR illumination after 3 days whereas 1.7-fold was found without NIR illumination after 7 days in comparison to PCL (pure). The current findings will be useful to provide a new crucial approach for preparing biocompatible multifunctional composite plasmonic nanofibers as a highly efficient distinct platform for photothermal therapies and promising bioimplants to overcome the loss of sensation after cancer surgery through nerve photobiomodulation.

Systematic review and meta-analysis of cardiac neurosis for development of clinical practice guidelines of Korean medicine.

Background: The development of clinical practice guidelines in traditional medicine requires evidence that sufficiently reflects the medical field. Cardiac neurosis is a disease that occurs because of problems in the autonomic nervous system and is characterized by symptoms of the circulatory system that are representative of autonomic dysfunction. In traditional medicine, the heart is considered to be involved in mental health problems, and cardiac neurosis is accompanied by a variety of mental symptoms. Furthermore, there is a categorized diagnosis for cardiac neurosis, and active empirical research is being conducted in China. Objective: This study aimed to systematically review and quantitatively synthesize the effects of Korean medicine treatments in patients with cardiac neurosis to develop evidence-based clinical practice guidelines for the treatment of autonomic dysfunction. Methods: Nine databases were searched for articles published before September 13, 2022. The methodological quality of the studies was assessed using the RoB tool. The primary outcomes were somatization, depression, anxiety, and effectiveness rate. The secondary outcome was the rate of adverse effects. Results: Based on a systematic literature review, 151 randomized controlled trials were selected and analyzed. For patients with cardiac neurosis, herbal medicine, combined treatment of herbal medicine and Western medicine, combined treatment of herbal medicine and acupuncture, acupuncture, and combined treatment of acupuncture and Western medicine showed better overall effects than Western medicine alone. Furthermore, the combined treatment of herbal medicine and psychotherapy and that of herbal medicine, psychotherapy, and Western medicine showed an overall better effect than the combined treatment of Western medicine and psychotherapy. Conclusion: A meta-analysis of articles revealed the effectiveness of Korean medicine treatments and verified the effectiveness of a Korean medicine treatment alone, Korean medicine combined treatment, and combined treatment of Korean medicine and Western medicine on cardiac neurosis. Limitations included the inability to verify the cause of high heterogeneity between studies and the poor quality of the included studies. Nevertheless, this systematic review and meta-analysis of cardiac neurosis showed that the disease concept of traditional medicine can also be organized based on the latest research. Future research related to traditional diseases such as these should be conducted. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022347992, identifier CRD42022347992.

A microscale 3D organ on a chip for recapitulating reciprocal neuroendocrine crosstalk between the hypothalamus and the pituitary gland.

Conventional 2D or even recently developed 3Din vitroculture models for hypothalamus and pituitary gland cannot successfully recapitulate reciprocal neuroendocrine communications between these two pivotal neuroendocrine tissues known to play an essential role in controlling the body's endocrine system, survival, and reproduction. In addition, most currentvitroculture models for neuroendocrine tissues fail to properly reflect their complex multicellular structure. In this context, we developed a novel microscale chip platform, termed the 'hypothalamic-pituitary (HP) axis-on-a-chip,' which integrates various cellular components of the hypothalamus and pituitary gland with biomaterials such as collagen and hyaluronic acid. We used non-toxic blood coagulation factors (fibrinogen and thrombin) as natural cross-linking agents to increase the mechanical strength of biomaterials without showing residual toxicity to overcome drawbacks of conventional chemical cross-linking agents. Furthermore, we identified and verified SERPINB2 as a reliable neuroendocrine toxic marker, with its expression significantly increased in both hypothalamus and pituitary gland cells following exposure to various types of toxins. Next, we introduced SERPINB2-fluorescence reporter system into loaded hypothalamic cells and pituitary gland cells within each chamber of the HP axis on a chip, respectively. By incorporating this SERPINB2 detection system into the loaded hypothalamic and pituitary gland cells within our chip platform, Our HP axis-on-chip platform can better mimic reciprocal neuroendocrine crosstalk between the hypothalamus and the pituitary gland in the brain microenvironments with improved efficiency in evaluating neuroendocrine toxicities of certain drug candidates.

Clinical Assessment of Thermotherapy Applications during Hepatectomy and Laparotomy in Sturgeon (Acipenser ruthenus): Impact on Bioparameter Variations Based on Liver Condition.

Surgical techniques are gaining attention for treating physical diseases in aquaculture and aquarium fish. Sturgeon is a suitable species for surgical experiments due to its industrial significance. Maintaining homeostasis is crucial during surgical procedures, and the liver plays a major role in immune regulation. High temperature is suggested to improve physiological activity and wound healing. This study investigated differences in hepatectomy sturgeons' tolerance and histopathological responses of internal organs. Moreover, this study investigated the effects of high temperatures on wound healing and hematopoietic recovery in fish undergoing surgical procedures. The liver condition was found to play a pivotal role in the analysis, and cortisol levels were affected by anesthesia. The results showed that high temperature facilitated hematopoietic recovery and wound healing, but excessive induction of physiological activity caused damage. Managing high temperatures and liver conditions induced a remarkable improvement in wound healing. However, anesthesia itself can be a significant stressor for fish, and wound healing requires a greater amount of energy. Further research is needed to understand the stress factors caused by surgical procedures and anesthesia and to promote animal welfare in fishery products.

Current status of nutritional provision and effects of nutritional support on the clinical outcomes of acute kidney injury requiring continuous renal replacement therapy in the surgical intensive care unit.

BACKGROUND AND OBJECTIVES: Patients with acute kidney injury requiring continuous renal replacement therapy are at high risk of malnutrition. Nutritional support is an important part of treatment for patients with critical illness admitted to the intensive care unit. We aimed to investigate the status of nutritional provision and the effects of nutritional support on clinical outcomes. METHODS AND STUDY DESIGN: Our institution's medical records (from January 1, 2020, to December 31, 2021) were analyzed in this retrospective cohort study. We included 43 patients aged >18 years who received continuous renal replacement therapy for acute kidney injury in the surgical intensive care unit. RESULTS: The demographic characteristics were similar between the survivor and non-survivor groups. The protein supply per body weight (0.88 ± 0.37 g/kg vs. 0.47 ± 0.53 g/kg, p = 0.029) and the proportion of patients who met the target protein level (58.9 ± 24.9% vs. 30.8 ± 34.9%, p = 0.022) were significantly higher in the survivor group. Approximately 79.1% of the patients had a high malnutrition risk with a modified Nutrition Risk in the Critically Ill score of ≥5. The lengths of hospital and intensive care unit stays were longer in the high nutritional risk group compared with that in the low nutritional risk group, but the result was not significant. CONCLUSIONS: The nutritional amount provided in patients with critical illness is significantly lesser than the recommended amount. Ensuring proper nutritional support can improve the clinical outcomes.

Soy Sauce Lowers Body Weight and Fat Mass in High-Fat Diet-Induced Obese Rats.

Soy sauce (SS) is a traditional fermented seasoning. Although fermented foods have diverse health beneficial effects, SS intake has been discouraged because of its high salt level. This study was designed to evaluate the antiobesity outcomes of SS and the potential involvement of salt content in SS by adding a high-salt group. Sprague-Dawley rats were randomly assigned into four groups: normal diet (ND, 10% fat of total kcal), high-fat diet (HD, 60% fat of total kcal), HD with salt water (HDSW, NaCl = 8%), and HD with SS (HDSS, NaCl = 8%). SS significantly decreased HD-induced body weight gain and lipogenic gene expression without affecting food consumption. Moreover, SS also reduced hepatic injury and lipid accumulation, and also improved hyperlipidemia. Furthermore, SS decreased the mRNA levels related to obesity-derived inflammatory responses, while HDSW did not change the levels of those markers. These observations indicate that SS ameliorates obesity in HD-fed obese rats by attenuating dyslipidemia. Moreover, SS might also have an anti-inflammatory effect in HD-induced obesity, which requires further investigation. Most importantly, SS offers these beneficial effects regardless of its high salt content, implying that different dietary salt sources lead to the distinct health outcomes. In conclusion, the findings of this study improve the understanding of the functional effect of SS.

Single neonatal estrogen implant sterilizes female animals by decreasing hypothalamic KISS1 expression.

Reproductive sterilization by surgical gonadectomy is strongly advocated to help manage animal populations, especially domesticated pets, and to prevent reproductive behaviors and diseases. This study explored the use of a single-injection method to induce sterility in female animals as an alternative to surgical ovariohysterectomy. The idea was based on our recent finding that repetitive daily injection of estrogen into neonatal rats disrupted hypothalamic expression of Kisspeptin (KISS1), the neuropeptide that triggers and regulates pulsatile secretion of GnRH. Neonatal female rats were dosed with estradiol benzoate (EB) either by daily injections for 11 days or by subcutaneous implantation of an EB-containing silicone capsule designed to release EB over 2-3 weeks. Rats treated by either method did not exhibit estrous cyclicity, were anovulatory, and became infertile. The EB-treated rats had fewer hypothalamic Kisspeptin neurons, but the GnRH-LH axis remained responsive to Kisspeptin stimulation. Because it would be desirable to use a biodegradable carrier that is also easier to handle, an injectable EB carrier was developed from PLGA microspheres to provide pharmacokinetics comparable to the EB-containing silicone capsule. A single neonatal injection of EB-microspheres at an equivalent dosage resulted in sterility in the female rat. In neonatal female Beagle dogs, implantation of an EB-containing silicone capsule also reduced ovarian follicle development and significantly inhibited KISS1 expression in the hypothalamus. None of the treatments produced any concerning health effects, other than infertility. Therefore, further development of this technology for sterilization in domestic female animals, such as dogs and cats is worthy of investigation.

Oral Ingestion of AP Collagen Peptide Leads to Systemic Absorption of Gly-Pro-Hyp, Alleviating H2O2-Induced Dermal Fibroblast Aging.

Collagen-derived dipeptides and tripeptides have various physiological activities. In this study, we compared the plasma kinetics of free Hyp, peptide-derived Hyp, Pro-Hyp, cyclo(Pro-Hyp), Hyp-Gly, Gly-Pro-Hyp, and Gly-Pro-Ala after ingestion of four different collagen samples: AP collagen peptide (APCP), general collagen peptide, collagen, and APCP and γ-aminobutyric acid (GABA) combination. Each peptide was measured by high-performance liquid chromatography and triple quadrupole mass spectrometer. We found that, among all the peptides that were analyzed, only Gly-Pro-Hyp was significantly increased after ingestion of APCP compared with that of general collagen peptides and collagen. In addition, ingestion of the APCP and GABA combination improved the absorption efficiency of Gly-Pro-Ala. Finally, we reveal that Gly-Pro-Hyp was effective for preventing H2O2-induced reduction in extracellular matrix (ECM)-related genes, COL1A, elastin, and fibronectin, in dermal fibroblasts. Taken together, APCP significantly enhances the absorption of Gly-Pro-Hyp, which might act as an ECM-associated signaling factor in dermal fibroblasts, and the APCP and GABA combination promotes Gly-Pro-Ala absorption. Clinical Trial Registration number: UMIN000047972.

Murine cytomegalovirus downregulates ERAAP and induces an unconventional T cell response to self.

The endoplasmic reticulum aminopeptidase associated with antigen processing (ERAAP) plays a crucial role in shaping the peptide-major histocompatibility complex (MHC) class I repertoire and maintaining immune surveillance. While murine cytomegalovirus (MCMV) has multiple strategies for manipulating the antigen processing pathway to evade immune responses, the host has also developed ways to counter viral immune evasion. In this study, we find that MCMV modulates ERAAP and induces an interferon γ (IFN-γ)-producing CD8+ T cell effector response that targets uninfected ERAAP-deficient cells. We observe that ERAAP downregulation during infection leads to the presentation of the self-peptide FL9 on non-classical Qa-1b, thereby eliciting Qa-1b-restricted QFL T cells to proliferate in the liver and spleen of infected mice. QFL T cells upregulate effector markers upon MCMV infection and are sufficient to reduce viral load after transfer to immunodeficient mice. Our study highlights the consequences of ERAAP dysfunction during viral infection and provides potential targets for anti-viral therapies.

Acupuncture Inhibits Morphine Induced-Immune Suppress via Antioxidant System.

Objectives: A powerful analgesic called Morphine causes addiction behaviors and immune suppression as a potential oxidative stressor. Acupuncture showed to inhibit oxidative stress-induced hepatic damage, regulate reactive oxygen species, and attenuate morphine addiction behaviors. Therefore, we investigated the potential effects of acupuncture on morphine-induced immune suppression. Materials and Methods: Rats received morphine intravenously through implanted catheters for 3, 7, or 21 days to determine the optimal condition for morphine-induced immune suppression. Second, we examined whether intravenous (iv.) or intraperitoneal (ip.) administration produced different results. Third, the effects of acupuncture in rats who received morphine for 21 days were investigated. Spleen and submandibular lymph node (S-LN) weights and natural killer (NK) cell activity were measured, and the white pulp diameter, total and cortical spleen thicknesses, and the number of lymphoid follicles in S-LNs were examined. The number of immunoreactive cells was also measured. Results: Decreased organ weights and increased atrophic changes were observed as morphine-induced immune suppression. However, dose-dependent increased immune suppression was not observed between 5.0 mg/kg and 10.0 mg/kg of morphine. And, 3-day withdrawal did not affect. Similar histopathological findings were observed in 5.0 and 10.0 ip. rats when compared to equal dosages of iv., respectively. The morphine induced-immune suppression evidenced by spleen and left S-LN weights, splenic NK cell activities, histopathological findings, and the immunoreactive cell number were normalized by acupuncture. Conclusion: These results indicate that acupuncture inhibits morphine-induced immune suppression, maybe via antioxidative action.

Near-Infrared Responsive Synergistic Chemo-Phototherapy from Surface-Functionalized Poly(ε-caprolactone)-Poly(d,l-lactic-co-glycolic acid) Composite Nanofibers for Postsurgical Cancer Treatment.

The combination of hyperthermia and chemotherapy has attracted significant attention in local cancer treatment following surgical resection. Pyrrole is a potent photothermal agent that can induce a temperature rise at different concentrations in the surrounding medium by absorbing near-infrared radiation (NIR). In this study, poly(ε-caprolactone) (PCL) and poly (d,l-lactic-co-glycolic acid) (PLGA) were used to make nanofibers using the electrospinning process. Then, pyrrole in different concentrations of (0.2, 0.4, and 0.6) M was attached to the surface of PCL-PLGA fiber mats by in situ polymerization, which was confirmed by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD) analysis. A concentration-dependent local temperature rise was observed using a FLIR camera under near-infrared (NIR) laser irradiation. For the hyperthermia effect, pyrrole concentration (0.06 M) was used for in vitro drug release studies and cell viability assays because under NIR irradiation (2 W/cm2, 3 min), it increased the local temperature to around 45 °C. In vitro drug release studies confirmed that NIR irradiation increased the diffusion rate of doxorubicin (DOX) by increasing the environmental temperature above the glass transition temperature of PLGA. In vitro cytotoxicity experiments further confirmed that PCL-PLGA-DOX/PPy fiber mats showed an enhanced inhibitory effect against CT26 and MCF7 cells by the combination of hyperthermia and chemotherapy.

Protective mechanisms of loquat leaf extract and ursolic acid against diabetic pro-inflammation.

The pharmacological effectiveness of loquat leaf extract (LE) and its important component, ursolic acid (UA), in the treatment of diabetes mellitus, has been well established in traditional medicine; however, the mechanism underlying their action is still unclear. We evaluated the protective effects of LE and UA against hyperglycemia-induced advanced glycation end product (AGE) formations and hepatic pro-inflammation. Oral administration of UA and LE at a dose of 50 mg/kg/day for 15 days yielded no significant hypoglycemic effect in diabetic db/db mice. UA and LE suppressed hepatic oxidative stress and AGE formation in diabetic mice, and this was followed by the downregulated mitogen-activated protein kinase signaling and nuclear factor κ B (NF-κB) activity. To identify the molecular target of LE and UA, a docking simulation was performed, and this predicted UA to bind to liver kinase B1 (LKB1), an upstream of AMP-activated protein kinase (AMPK)/transcription factor forkhead box O3 (FOXO3) axis. UA reversed the high-glucose-induced downregulation of LKB1-AMPK1-FOXO3 activation and antioxidant gene transcription. These findings demonstrated the antioxidant and anti-inflammatory effects of UA and LE against hyperglycemia-induced hepatic inflammation. Furthermore, we speculate that the LKB1/AMPK/FOXO3 pathway is a potential target responsible for these beneficial effects of LE and UA.

Impact of l-Carnitine Supplementation on Liver Enzyme Normalization in Patients with Chronic Liver Disease: A Meta-Analysis of Randomized Trials.

The effectiveness of l-carnitine in chronic liver disease remains controversial. We conducted this meta-analysis to assess the efficacy of various forms of l-carnitine in the treatment of chronic liver disease. METHODS: We searched the Cochrane Library, EMBASE, KMBASE, and Medline databases for all relevant studies published until April 2022 that examined the ability of l-carnitine or its derivatives to normalize liver enzymes in patients with chronic liver disease. We performed meta-analyses of the proportion of patients with alanine aminotransferase (ALT) normalization and post-treatment serum aspartate aminotransferase (AST) and ALT levels. A random effects model was used for meta-analyses. RESULTS: Fourteen randomized controlled trials (1217 patients) were included in this meta-analysis. The proportion of patients in whom ALT normalized was higher in the carnitine-orotate treatment group than in the control group (pooled odds ratio (OR), 95% confidence interval (CI) = 4.61 (1.48-14.39)). The proportion of patients in whom ALT normalized was also higher among those who received the carnitine-orotate complex, a combination of carnitine-orotate, biphenyl dimethyl dicarboxylate, and other minor supplementary compounds than in those who did not without significant heterogeneity (pooled OR (95% CI) = 18.88 (7.70-46.27); df = 1; p = 0.51; I2 = 0%). l-carnitine supplementation effectively lowered serum ALT levels compared to controls (pooled mean difference (95% CI) = -11.99 (-22.48 to -1.49)). CONCLUSIONS: l-carnitine supplementation significantly lowered ALT and AST levels and normalized ALT levels in patients with chronic liver disease.

ω-3 fatty acid-enriched parenteral nutrition shortens hospital stay in acute variceal bleeding cirrhotic patients.

ABSTRACT: Acute variceal bleeding, a crucial complication of liver cirrhosis requires high energy expenditures but gastrointestinal bleeding limits enteral feeding in the acute stage. We investigated the safety and efficacy of ω-3 fatty acid-enriched parenteral nutrition in acute variceal bleeding patients.In this retrospective study, a total of 208 cirrhotic patients with acute variceal bleeding who underwent parenteral nutrition in the absence of enteral nutrition were enrolled. Among the patients, 86 patients received ω-3 fatty-acid-enriched parenteral nutrition. The primary endpoint was to evaluate the duration of hospital stay and the presence of clinical complications of liver cirrhosis.The mean age of the patients enrolled was 54.9 years-old and 185 patients (88.9%) were male. The cause of liver cirrhosis, Child-Pugh score and comorbidities were statistically not different. Patients with ω-3 enriched parenteral nutrition had a significantly lower systolic blood pressure and total bilirubin levels. The difference in the in-hospital mortality (P = .813) or rate of complications (P = .880) was not statistically significant. The duration of hospital stay was significantly shorter in the patients who underwent ω-3 fatty acid-enriched parenteral nutrition (10.7 ±â€Š7.3 vs 7.9 ±â€Š4.2 days, P = .001).In liver cirrhosis patients with acute variceal bleeding, ω-3 fatty acid-enriched parenteral nutrition significantly decreased the length of hospital stay. Further prospective studies to consolidate these findings are warranted.

Nanogap-containing thermo-plasmonic nano-heaters for amplified photo-triggered tumor ablation at low laser power density.

Herein, nanogap amplified plasmonic heat-generators are fabricated by decorating Pt nanodots on gold nanospheres (GNSs@Pt@mPEG) by maintaining strategic nano-gaps (1-2 nm) and studied precisely for plasmonic photothermal therapy (PPTT) of colon cancer by passive tumor targeting. The surface modification of GNSs@Pt with poly(ethylene glycol) methyl ether thiol (mPEG) increases their accumulation in tumor cells and hence the GNSs@Pt@mPEG stay at the tumor site for a longer time. The nanogap amplified GNSs@Pt@mPEG (O.D. = 4.0) generated high plasmonic photothermal hyperthermia and utilized a low NIR power density (0.36 W cm-2) for the elimination of tumor cells in only 150 s of irradiation time and shows excellent colloidal and photo-stability. The predominant distribution of GNSs@Pt@mPEG caused effective tumor cell death and promoted uniform treatment on tumor sites. In vivo studies demonstrated that the GNSs@Pt@mPEG have very low toxicity, high biocompatibility, and thermal stability, stay longer at the tumor site, induce tumor cell death without side effects, and show significantly less uptake in other organs except for the spleen. The significant accumulations and longer stay suggested that they are favorable for tumor passive uptake and the possibility of enhanced PPTT after intravenous administration. The nano-particles were stable up to O.D. 200 and have at least 12 months shelf-life without losing colloidal stability or photothermal efficacy. These findings lay the groundwork for using GNSs@Pt@mPEG as a NIR light-responsive PPTT agent and demonstrated their potential for further use in clinical applications.

Impact of short-chain fatty acid supplementation on gut inflammation and microbiota composition in a murine colitis model.

Short-chain fatty acids (SCFAs) play a pivotal role in maintaining intestinal homeostasis. We aimed to investigate the effects of SCFA supplementation on gut inflammation and microbiota composition in a murine colitis model. Mice were fed with sodium butyrate or a mixture of SCFAs in the drinking water for 2 weeks, followed by 2% dextran sulfate sodium (DSS) for 7 d. After euthanasia, mouse colons were extracted to examine histological findings. Flow cytometry of the mouse colon tissues was performed to assess T cell differentiation. Changes in gut microbiota were assessed by high-throughput sequencing of the mouse feces. There were no significant differences in weight change, colonic length, or histologic inflammation score between the DSS, butyrate, and SCFA mix groups. However, flow cytometry revealed that both the expression of CD4+Foxp3+ regulatory T cells and of IL-17-producing T cells were increased in the butyrate and SCFA mix groups. Microbial compositions of the butyrate and SCFA mix groups were significantly different from those of the control and DSS groups in principal coordinate analysis. Relative abundances of the phyla Verrucomicrobia and Proteobacteria, species Akkermansia muciniphila and Escherichia fergusonii were increased in the butyrate and SCFA mix groups. Genera Roseburia and Lactobacillus showed a negative correlation with the degree of colitis, whereas genera Escherichia and Mucispirillum showed a positive correlation. SCFA supplementation did not result in a significant reduction in colon inflammation, but it promoted both regulatory T cell and IL-17-producing T cell expression, and increased both protective and aggressive gut microbiota.

Protective and therapeutic effect of (S)-ginsenoside F1 on peripheral nerve degeneration targeting Schwann cells: a pharmaco-neuroanatomical approach.

Damaged peripheral nerves undergo peripheral neurodegenerative processes that are essential for the nerve regeneration. Peripheral neurodegenerative diseases, including diabetic peripheral neuropathy, are induced by irreversible nerve damage caused by abnormal peripheral nerve degeneration. However, until now, there have been no effective therapeutic treatments for these diseases. Ginsenosides are the most pharmacologically active compounds in Panax ginseng, and are being actively studied. Ginsenosides have a variety of effects, including neuroprotective, antioxidative, anti-cytotoxic, and anti-inflammatory effects. Here, we investigated the efficacy of 18 ginsenosides. We then tested the ability of the most effective ginsenoside, (S)-ginsenosides F1 (sF1), to inhibit peripheral neurodegenerative processes using mouse sciatic ex vivo culture, and several morphological and biochemical indicators. Our results suggest that sF1 could effectively protect Schwann cells against peripheral nerve degeneration.

Caterpillar Medicinal Mushroom, Cordyceps militaris (Ascomycota), Attenuates Aß1-42-Induced Amyloidogenesis and Inflammatory Response by Suppressing Amyloid Precursor Protein Progression and p38 MAPK/JNK Activation.

The deposition of amyloid beta (Aß) is a neuropathological feature of Alzheimer's disease (AD). Cordyceps militaris is an edible medicinal fungus in Asian countries with antioxidative, antiaging, antitumor, and immunomodulatory effects. In this study, we investigated the neuroprotective mechanisms of C. militaris in the brain of Aß1-42-injected AD mice. An intracerebroventricular injection of Aß1-42 (total 3 µg/mouse) resulted in neurological damage, including amyloidogenesis and neuroinflammation; however, C. militaris attenuated Aß1-42-induced amyloidogenesis and inflammatory responses. Oral administration of C. militaris at concentrations of 100 and 200 mg/kg suppressed acetylcholinesterase activity. In addition, C. militaris treatment downregulated amyloid precursor protein levels, with a decrease in ß-secretase activity. Moreover, C. militaris significantly enhanced the expression of brain-derived neurotrophic factor. Furthermore, C. militaris-administered groups had inactivated inflammatory responses by downregulation of inducible nitric oxide synthase and cyclooxygenase-2 protein expression. The injection of Aß1-42 resulted in the activation of p38 MAPK and c-Jun N-terminal kinase, which was rescued by C. militaris. These results suggest that C. militaris has a protective effect against Aß1-42-induced neurological damage.

Oral Intake of Enzymatically Decomposed AP Collagen Peptides Improves Skin Moisture and Ceramide and Natural Moisturizing Factor Contents in the Stratum Corneum.

The stratum corneum (SC) is the outermost layer of the epidermis and plays an important role in maintaining skin moisture and protecting the skin from the external environment. Ceramide and natural moisturizing factor (NMF) are the major SC components that maintain skin moisture. In this study, we investigated whether the oral intake of enzymatically decomposed AP collagen peptides (APCPs) can improve skin moisture and barrier function by assessing changes in the ceramide and NMF contents in the SC after APCP ingestion with the aim to develop a skin functional food. Fifty participants orally ingested APCP (1000 mg) or placebo for 12 weeks, and then, skin hydration and skin texture were evaluated. SC samples were collected to analyze skin scaling, ceramide, and NMF contents. Participants in the APCP group exhibited improved skin moisture content by 7.33% (p = 0.031) and roughness by -4.09% (p = 0.036) when compared with those in the placebo group. NMF content; the amounts of amino acids (AA), including glycine and proline; and AA derivatives were significantly increased in the APCP group (31.98 µg/mg protein) compared to those in the placebo group (-16.01 µg/mg protein) (p = 0.006). The amounts of total ceramides and ceramide subclasses were significantly higher in the APCP group than in the placebo group (p = 0.014). In conclusion, our results demonstrate that APCP intake improves skin moisture and increase the ceramide and NMF contents in the SC, thereby enhancing the skin barrier function.