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Background/Aim: In a previous report, our group showed that oral administration of lipopolysaccharides (LPS) from Pantoea agglomerans can prevent the progression of streptozotocin (STZ)-induced diabetes-related cognitive dysfunction (DRCD) in mice without causing significant sideeffects. However, the treatment effects of oral administration of LPS to DRCD remain unknown. Materials and Methods: We modified our previous animal experimental model to investigate whether oral administration of LPS can recover cognitive function after DRCD onset. Results: The Morris water maze (MWM) revealed a significant decrease in learning and memory abilities at 13 days after intracerebroventricular administration of STZ, thereby providing evidence of the occurrence of DRCD in the animal model. Oral administration of LPS (1 mg/kg per day) started after cognitive impairment was observed. After 28 days of treatment, mice receiving LPS via the oral route showed significant recovery of spatial learning ability, a symptom of early dementia, while only a trend toward recovery was seen for spatial memory compared to the untreated group. Conclusion: These results, limited to MWM, suggest that oral administration of LPS is a promising therapeutic strategy for restoring decreased spatial learning ability. [ABSTRACT FROM AUTHOR]

Three hyperimmune egg-based formulations rich in immunoglobulin Y (IgY) were orally administered (daily, for up to 90 days) to C57BL/6 mice that were not microbially challenged. The serum levels of 32 cytokines were quantified every 30 days. Histopathology, hematology, and serum biochemistry investigations were also performed. As a sign of increased immune activity, lymphohistiocytic infiltrates were detected in the digestive tract and the liver after 30, 60, and 90 days of treatment. These infiltrates were also present in the lungs after 30 and 60 days, but not at 90 days. Blood analysis indicated systemic inflammation after 30 days of treatment: increases in pro-inflammatory cytokines, glycemia, total serum proteins, ALT, and ALP. After 60 and 90 days of treatment, the analyzed blood parameters showed mixed signs of both increased and decreased inflammation. The increased cytokines, which varied with formulation and time of exposure, indicated a combination of mostly Th17- and Th2-type immune responses. As the mice were healthy and housed in standardized sanitary conditions, and were not microbially challenged, the data were consistent with an interaction of IgY with the gut-associated lymphoid tissue as the main mechanism of action. This interaction generated a local immune response, which subsequently induced a systemic response. [ABSTRACT FROM AUTHOR]

• In vivo-evaluated 5-ASA-HbNPs as a colon-specific prodrug for treatment of experimental colitis. • HbNPs conjugation is an efficient way to increase the therapeutic effect and to reduce the adverse effects of 5-ASA. • HbNPs acted as not only a pro-moiety but also a therapeutically active agent. • Mucoadhesive property of this colonic nano-delivery system contributed to the treatment of IBD. The oral formulation design for colon-specific drug delivery brings some therapeutic benefits in the ulcerative colitis treatment. We recently reported the specific delivery of hemoglobin nanoparticles-conjugating 5-aminosalicylic acid (5-ASA-HbNPs) to the inflamed site. In the current study, the therapeutic effect of the 5-ASA-HbNPs formulation was confirmed in vivo. This evaluation of 5-ASA-HbNPs not only shows longer colonic retention time due to adhesive properties, also provides full support for it as compared with free 5-ASA. It was considered as a suitable bio-adhesive nanoparticle with mucoadhesive property to pass through the mucus layer and accumulate into the mucosa. In UC model mice, a two-fold decrease in the disease activity indexes and colon weight/length ratios was significantly observed in the group treated with 5-ASA-HbNPs. This group received one percent of the standard dosage of 5-ASA (50 μg/kg), while, a similar result was observed for a significant amount of free 5-ASA (5 mg/kg). Furthermore, microscopic images of histological sections of the extracted colons demonstrated that the 5-ASA-HbNPs and 5-ASA groups displayed instances of inflammatory damage within the colon. However, in comparison to the colitis group, the extent of this damage was relatively moderate, suggesting 5-ASA-HbNPs improved therapeutic efficacy with the lower dosage form. [Display omitted] [ABSTRACT FROM AUTHOR]

The gut microbiota is closely associated with human health, and alterations in gut microbiota can influence various physiological and pathological activities in the human body. Therefore, microbiota regulation has become an important strategy in current disease treatment, albeit facing numerous challenges. Nanomaterials, owing to their excellent protective properties, drug release capabilities, targeting abilities, and good biocompatibility, have been widely developed and utilized in pharmaceuticals and dietary fields. In recent years, significant progress has been made in research on utilizing nanomaterials to assist in regulating gut microbiota for disease intervention. This review explores the latest advancements in the application of nanomaterials for microbiota regulation and offers insights into the future development of nanomaterials in modulating gut microbiota. [ABSTRACT FROM AUTHOR]

Turmeric (Curcuma longa L.), a spice and food coloring agent in food preparation, contains a carotenoid pigment called curcumin. Curcumin has attracted extensive research interest owing to its health benefits, ranging from neuroprotection to chemoprevention and antioxidation. It also exhibits anti-cancer effects due to its capacity to inhibit cancer cell proliferation and stimulate apoptosis. However, the health-promoting effects of curcumin are limited by its poor aqueous solubility and low oral bioavailability. This article presents an overview of the latest understanding of the biological effects of curcumin and its use as a food additive in the development of functional food products. [ABSTRACT FROM AUTHOR]

Single‐domain antibodies (sdAbs), such as VHHs, are increasingly being developed for gastrointestinal (GI) applications against pathogens to strengthen gut health. However, what constitutes a suitable developability profile for applying these proteins in a gastrointestinal setting remains poorly explored. Here, we describe an in vitro methodology for the identification of sdAb derivatives, more specifically divalent VHH constructs, that display extraordinary developability properties for oral delivery and functionality in the GI environment. We showcase this by developing a heterodivalent VHH construct that cross‐inhibits the toxic activity of the glycosyltransferase domains (GTDs) from three different toxinotypes of cytotoxin B (TcdB) from lineages of Clostridium difficile. We show that the VHH construct possesses high stability and binding activity under gastric conditions, in the presence of bile salts, and at high temperatures. We suggest that the incorporation of early developability assessment could significantly aid in the efficient discovery of VHHs and related constructs fit for oral delivery and GI applications. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the impact of different functional stabilizers on in vitro/in vivo drug performances after oral administration of drug nanocrystals. Quercetin nanocrystals (QT-NCs) respectively stabilized by five types of functional stabilizers, including hydroxypropyl methyl cellulose E15 (HPMC E15), poloxamer 407 (P407), poloxamer 188 (P188), D-α-tocopherol polyethylene glycol succinate (TPGS), and glycyrrhizin acid (GL), were fabricated by wet media milling technique. The particle size, morphology, physical state, drug solubility, drug dissolution in vitro, and orally pharmacokinetic behaviors of all QT-NCs were investigated. All QT-NCs with similar particle size about 200 nm were obtained by controlling milling speed and milling time. No significant differences in particles shape and crystalline nature were found for QT-NCs stabilized by different functional stabilizers. But the solubility and dissolution of QT-NCs were significantly influenced by the different functional stabilizers. The AUC0∼t of all QT-NCs after oral administration was in the following order: QT-NCs/P188 ≈ QT-NCs/HPMC E15 > QT-NCs/GL > QT-NCs/P407 ≈ QT-NCs/TPGS, and the Cmax showed an order of QT-NCs/P407 > QT-NCs/P188 ≈ QT-NCs/GL > QT-NCs/HPMC E15 > QT-NCs/TPGS. Both of QT-NCs/P407 and QT-NCs/TPGS exhibited faster oral absorption with Tmax at 0.5 h and 0.83 h, respectively, while the other three QT-NCs (QT-NCs/P188, QT-NCs/GL and QT-NCs/HPMC E15) showed a relatively slow absorption with same Tmax at 5.33 h. The longest MRT0∼t (11.72 h) and t1/2z (32.22 h) were observed for QT-NCs/HPMC E15. These results suggested that the different functional stabilizers could significantly influence on drug solubility, drug dissolution in vitro and orally pharmacokinetic behavior of QT-NCs, and it is possible to alter the drug dissolution in vitro, oral absorption and drug retention in vivo by changing the type of functional stabilizers in NCs preparation. [ABSTRACT FROM AUTHOR]

Oral administration is the most simple, noninvasive, convenient treatment. With the increasing demands on the targeted drug delivery, the traditional oral treatment now is facing some challenges: 1) biologics how to implement the oral treatment and ensure the bioavailability is not lower than the subcutaneous injections; 2) How to achieve targeted therapy of some drugs in the gastrointestinal tract? Based on these two issues, drug delivery microrobots have shown great application prospect in oral drug delivery due to their characteristics of flexible locomotion or driven ability. Therefore, this paper summarizes various drug delivery microrobots developed in recent years and divides them into four categories according to different driving modes: magnetic-controlled drug delivery microrobots, anchored drug delivery microrobots, self-propelled drug delivery microrobots and biohybrid drug delivery microrobots. As oral drug delivery microrobots involve disciplines such as materials science, mechanical engineering, medicine, and control systems, this paper begins by introducing the gastrointestinal barriers that oral drug delivery must overcome. Subsequently, it provides an overview of typical materials involved in the design process of oral drug delivery microrobots. To enhance readers' understanding of the working principles and design process of oral drug delivery microrobots, we present a guideline for designing such microrobots. Furthermore, the current development status of various types of oral drug delivery microrobots is reviewed, summarizing their respective advantages and limitations. Finally, considering the significant concerns regarding safety and clinical translation, we discuss the challenges and prospections of clinical translation for various oral drug delivery microrobots presented in this paper, providing corresponding suggestions for addressing some existing challenges.

Mingtang Zeng,1,* Maozhu Liu,2,* Xuelin Tao,1,* Xi Yin,1 Chao Shen,1 Xueyan Wang1 1Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xueyan Wang, Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Email wxy1226@126.comAbstract: Inflammation involves complex immune responses where cytokines such as TNF-α, IL-1, and IL-6 promote vasodilation and increased vascular permeability to facilitate immune cell migration to inflammation sites. Persistent inflammation is linked to diseases like cancer, arthritis, and neurodegenerative disorders. Although oral anti-inflammatory drugs are favored for their non-invasiveness and cost-effectiveness, their efficacy is often compromised due to gastrointestinal degradation and limited bioavailability. Recent advancements highlight the potential of extracellular vesicles (EVs) as nanocarriers that enhance drug delivery by encapsulating therapeutic agents, ensuring targeted release and reduced toxicity. These EVs, derived from dietary sources and cell cultures, exhibit excellent biocompatibility and stability, presenting a novel approach in anti-inflammatory therapies. This review discusses the classification and advantages of orally administered EVs (O-EVs), their mechanism of action, and their emerging role in treating inflammatory conditions, positioning them as promising vectors in the development of innovative anti-inflammatory drug delivery systems.Keywords: extracellular vesicles, anti-inflammatory, drug delivery systems, food, oral administration

Abstract Background Microsponges are one of the advanced drug delivery systems that facilitates precise and controlled release of active ingredients that are suitable for topical and oral use. These porous microspheres are typically sized between 5 and 300 μm, offer benefits including controlled release, stability, and minimized side effects. Manufacturing techniques like quasi-emulsion solvent diffusion and liquid–liquid suspension polymerization are usually employed to prepare microsponges, although various challenges arise from the use of potentially hazardous organic solvents. Main body Microsponges possess distinct traits such as extended drug release, formulation flexibility, and high drug loading capacity. Entrapment of drugs requires considerations of solubility, stability, and miscibility, while evaluation methods encompass production yield and particle size analysis. Their applications range from dermatological to biopharmaceutical delivery, with diverse products utilizing this technology. Ongoing innovations about microsponges are evident in patents concerning medical dressings and hyaluronic acid delivery systems. Conclusion Microsponges present a promising avenue in drug delivery, despite many challenges. Current review addresses on limitations and diverse products highlighting commercial viability. Patent activity signifies continued interest, suggesting significant potential for enhancing patient care.

Abstract Radiation-induced intestinal injury is the most common side effect during radiotherapy of abdominal or pelvic solid tumors, significantly impacting patients’ quality of life and even resulting in poor prognosis. Until now, oral application of conventional formulations for intestinal radioprotection remains challenging with no preferred method available to mitigate radiation toxicity in small intestine. Our previous study revealed that nanomaterials derived from spore coat of probiotics exhibit superior anti-inflammatory effect and even prevent the progression of cancer. The aim of this work is to determine the radioprotective effect of spore coat (denoted as spore ghosts, SGs) from three clinically approved probiotics (B.coagulans, B.subtilis and B.licheniformis). All the three SGs exhibit outstanding reactive oxygen species (ROS) scavenging ability and excellent anti-inflammatory effect. Moreover, these SGs can reverse the balance of intestinal flora by inhibiting harmful bacteria and increasing the abundance of Lactobacillus. Consequently, administration of SGs significantly reduce radiation-induced intestinal injury by alleviating diarrhea, preventing X-ray induced apoptosis of small intestinal epithelial cells and promoting restoration of barrier integrity in a prophylactic study. Notably, SGs markedly improve weight gain and survival of mice received total abdominal X-ray radiation. This work may provide promising radioprotectants for efficiently attenuating radiation-induced gastrointestinal syndrome and promote the development of new intestinal predilection.

Adequate bowel preparation is a prerequisite for colonoscopy， and chronic constipation （CC） is one of the important influencing factors. In recent years， scholars have paid more and more attention to bowel preparation for CC. In this article， the selection of intestinal detergents before colonoscopy for CC was summarized according to literature review. The effectiveness and safety of each protocol were assessed to provide reference for clinical practice， improve the quality of bowel preparation for CC and deliver timely tertiary prevention for colorectal cancer.

Type 2 diabetes mellitus is a prevalent metabolic disease, posing a considerable threat to public health. Oligonucleotide drugs have proven to be a promising field of therapy for the diseases. In this study, we reported that a herbal small RNA (sRNA), JGL‐sRNA‐h7 (B34735529, F1439.L002444.A11), could exhibit potent hypoglycemic effects by targeting glucose‐6‐phosphatase. Oral administration of sphingosine (d18:1)‐JGL‐sRNA‐h7 bencaosomes ameliorated hyperglycemia and diabetic kidney injury better than metformin in db/db mice. Furthermore, glucose tolerance was also improved in sphingosine (d18:1)‐JGL‐sRNA‐h7 bencaosomes‐treated beagle dogs. Our study indicates that JGL‐sRNA‐h7 could be a promising hypoglycemic oligonucleotide drug. [ABSTRACT FROM AUTHOR]

Background: Microsponges are one of the advanced drug delivery systems that facilitates precise and controlled release of active ingredients that are suitable for topical and oral use. These porous microspheres are typically sized between 5 and 300 μm, offer benefits including controlled release, stability, and minimized side effects. Manufacturing techniques like quasi-emulsion solvent diffusion and liquid–liquid suspension polymerization are usually employed to prepare microsponges, although various challenges arise from the use of potentially hazardous organic solvents. Main body: Microsponges possess distinct traits such as extended drug release, formulation flexibility, and high drug loading capacity. Entrapment of drugs requires considerations of solubility, stability, and miscibility, while evaluation methods encompass production yield and particle size analysis. Their applications range from dermatological to biopharmaceutical delivery, with diverse products utilizing this technology. Ongoing innovations about microsponges are evident in patents concerning medical dressings and hyaluronic acid delivery systems. Conclusion: Microsponges present a promising avenue in drug delivery, despite many challenges. Current review addresses on limitations and diverse products highlighting commercial viability. Patent activity signifies continued interest, suggesting significant potential for enhancing patient care. [ABSTRACT FROM AUTHOR]

The current research aimed at assessing the effects of different levels of Thymol on blood, feeding and survival factors in Oncorhinchus mykiss against Yersinia ruckeri. In this order, three experimental treatments including control (fed with commercial food), first treatment (commercial food with 0.5 percent Thymol) and second treatment (commercial food with one percent Thymol) were used with three replications for each treatment within a factorial analysis for completely randomized design. Then, fish were fed for seven weeks using associated diets. The result showed that different levels of Thymol had no significant effect on survival rate of Oncorhinchus mykiss (P>0.05). Regarding blood indices before the challenge, we found that the 0.5 percent Thymol had no significant effect, however, the one percent Thymol treatment showed significant difference (P<0.05) which caused an increase in the amount of hemoglobin and the concentration of intraglobulin hemoglobin. Measuring blood indices after the challenge, however, showed no significant different. The comparison of growth indices among different Thymol treatments showed that the 0.5 percent Thymol had significant effect on final weight, weight gain, special growth rate, protein yield ratio and food conversion factor compared to the control and one percent Thymol treatments. The result from current study showed that Thymol stimulates growth and improves nutritional conditions in fish, especially rainbow trout. [ABSTRACT FROM AUTHOR]

The therapeutic potential of delta9-tetrahydrocannabinol (THC), a primary cannabinoid in the cannabis plant, has led to its development into oral medical products for treating various conditions. However, THC, being a psychoactive substance, can lead to addiction if taken in inappropriate amounts. Thus, studying the pharmacokinetics of THC is crucial for understanding how the drug behaves in the body after administration. This study aims to develop a multi-compartmental model to investigate the pharmacokinetics of medical THC and its metabolites after oral administration. Using the law of mass action, the model was converted into ordinary differential equations (ODEs) to describe the rate of concentration changes of THC and its metabolites in each compartment. The nonstandard finite difference (NSFD) method was then applied to construct numerical solution schemes, which were implemented in MATLAB along with estimated pharmacokinetic rate constants. The results demonstrate that the simulation curves depicting the plasma concentration–time profiles of THC and 11-hydroxy-THC (THC-OH) closely resemble actual data samples, indicating the model's accuracy. Moreover, the model predicts the pharmacokinetics of THC and its metabolites in various tissues. Consequently, this model serves as a valuable tool for enhancing our understanding of the pharmacokinetics of THC and its metabolites, guiding dosage adjustments, and determining administration durations for oral medical THC. [ABSTRACT FROM AUTHOR]

Radiation-induced intestinal injury is the most common side effect during radiotherapy of abdominal or pelvic solid tumors, significantly impacting patients' quality of life and even resulting in poor prognosis. Until now, oral application of conventional formulations for intestinal radioprotection remains challenging with no preferred method available to mitigate radiation toxicity in small intestine. Our previous study revealed that nanomaterials derived from spore coat of probiotics exhibit superior anti-inflammatory effect and even prevent the progression of cancer. The aim of this work is to determine the radioprotective effect of spore coat (denoted as spore ghosts, SGs) from three clinically approved probiotics (B.coagulans, B.subtilis and B.licheniformis). All the three SGs exhibit outstanding reactive oxygen species (ROS) scavenging ability and excellent anti-inflammatory effect. Moreover, these SGs can reverse the balance of intestinal flora by inhibiting harmful bacteria and increasing the abundance of Lactobacillus. Consequently, administration of SGs significantly reduce radiation-induced intestinal injury by alleviating diarrhea, preventing X-ray induced apoptosis of small intestinal epithelial cells and promoting restoration of barrier integrity in a prophylactic study. Notably, SGs markedly improve weight gain and survival of mice received total abdominal X-ray radiation. This work may provide promising radioprotectants for efficiently attenuating radiation-induced gastrointestinal syndrome and promote the development of new intestinal predilection. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is one of the most common malignant tumors in the world with complex etiology, high tumor heterogeneity, and low efficacy of treatment. The establishment of an animal model that is close to the clinical situation of hepatocellular carcinoma and can be successfully modeled many times is of great significance to the study of the pathogenesis, diagnosis and treatment of hepatocellular carcinoma. We used Diethylnitrosamine (DEN) to induce hepatocellular carcinoma in rodents and compared four models of DEN-induced hepatocellular carcinoma. Group C (Control): rats were fed a standard laboratory rat diet and freely drank normal water. Group P (Peritoneal injection): rats were administered an IP injection (50 mg/kg/week) between 5 and 23 weeks after birth. Ten microliter of DEN solution would be injected per g of rat. Group O (DEN-Fed group): rats were allowed unrestricted access to water contaminated with 0.01 % DEN between the ages of 7 and 15 weeks. 0.2 mL of DEN drinking water was consumed per gram of rat. Group P+O (Combined peritoneal injection and Oral feeding): rats were administered an IP injection (50 mg/kg) at weeks 3 and 5 post-birth, and they freely drank water contaminated with 0.012 % DEN between weeks 7 and 14 post-birth. We used an ultrasound scan, biochemical testing, haematoxylin, and eosin staining, Masson staining, Wolf scarlet staining, Ki67, CD34, a-SMA, CD8, and CD68 staining to compare between groups. Liver dissection and ultrasound scan showed that compared to other groups, the liver of Group P+O was darker in color, with more grey-white cancer nodules and larger localized tumors, and the structure of the tumors was slightly disorganized, with the elastography hardness of the middle lobe and the right lobe was slightly increased. The alanine aminotransferase and total bilirubin of Group P+O were higher than those of Group O but lower than those of Group P. Haematoxylin and eosin staining showed that the tumors of Group P+O were large, with large tumor cords and pseudo-glandular, the degree of differentiation was medium and surrounded by more fatty lesions. We conclude that combined DEN treatment is more effective, stable, and has the advantage of multiple modalities, leading to faster tumor formation. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila is one of the major freshwater fish pathogens. In the current study, a cocktail of D6 and CF7 phages was given orally to Labeo rohita to assess phage survival in fish organs as well as to determine the therapeutic efficacy of phage treatment against fish mortality caused by A. hydrophila. In the phage-coated feed, prepared by simple spraying method, phage counts were quite stable for up to 2 months with a decline of ≤ 0.23 log10 and ≤ 1.66 log10 PFU/g feed during 4 oC and room temperature storage. Throughout the experimental period of 7 days, both phages could be detected in the gut of fish fed with phage-coated feed. Besides, both CF7 and D6 phages were also detected in fish kidneys indicating the ability of both the phage to cross the intestinal barrier. During challenge studies with LD50 dose of A. hydrophila, phage cocktail doses of 1 × 106 – 1 × 108 PFU/g feed prevented the mortality in L. rohita with relative percentage survival (RPS) of 8.7–65.2. When challenged with LD90 dose of A. hydrophila, an RPS value of 28.6 was obtained at a phage cocktail dose of 1 × 108 PFU/g feed. The RPS data showed that orally-fed phage cocktail protected the fish against the mortality caused by A. hydrophila in a dose-dependent manner. Simple practical approaches for phage cocktail development, medicated feed preparation and oral administration along with phage survival and protection data make the current study useful for farmer-level application. [ABSTRACT FROM AUTHOR]

In recent years, increasing interest has been accorded to polyester-based polymer microstructures, driven by their promising potential as advanced drug delivery systems. This study presents the preparation and characterization of new polymeric microparticles based on poly(ethylene brassylate-co-squaric acid) loaded with norfloxacin, a broad-spectrum antibiotic. Polymacrolactone was synthesised in mild conditions through the emulsion polymerization of bio-based and renewable monomers, ethylene brassylate, and squaric acid. The microparticles were obtained using the precipitation technique and subsequently subjected to comprehensive characterization. The impact of the copolymer/drug ratio on various properties of the new system was systematically evaluated, confirming the structure of the copolymer and the encapsulation of norfloxacin. The microspheres are approximately spherical and predominantly homogeneously distributed. The average hydrodynamic diameter of the microparticles falls between 400 and 2000 nm, a decrease that is observed with the increase in norfloxacin content. All samples showed good encapsulation efficiency and drug loading capacity, with the highest values obtained for microparticles synthesised using an equal ratio of copolymer and drug. In vitro drug release results disclose that norfloxacin molecules are released in a sustained biphasic manner for up to 24 h. Antimicrobial activity was also studied, with samples showing very good activity against E. coli and moderate activity against S. aureus and E. faecalis. In addition, HDFA human fibroblast cell cultures demonstrated the cytocompatibility of the microparticles. [ABSTRACT FROM AUTHOR]

Adequate bowel preparation is a prerequisite for colonoscopy, and chronic constipation (CC) is one of the important influencing factors. In recent years, scholars have paid more and more attention to bowel preparation for CC. In this article, the selection of intestinal detergents before colonoscopy for CC was summarized according to literature review. The effectiveness and safety of each protocol were assessed to provide reference for clinical practice, improve the quality of bowel preparation for CC and deliver timely tertiary prevention for colorectal cancer. [ABSTRACT FROM AUTHOR]

This study investigated the effect of oral bovine serum albumin (BSA) on plasma amino acid profile and growth performance in blunt snout bream fed high‐fat and high‐energy diets. A total of 360 fish (average weight: 45.84 ± 0.07 g) were randomly divided into three groups in four replicates and fed with the control, high‐fat diet (HFD), and high‐energy diet (HED), respectively. After 12 weeks of feeding, fish were orally administered with 10% BSA for 10 h, with the blood and liver sample obtained at 10 h. The results showed no remarkable difference (p > 0.05) in final weight, weight gain rate, feed conversion ratio, protein efficiency ratio, and daily growth rate among dietary treatments. However, fish fed HFD and HED obtained significantly higher energy and nitrogen retention content than the control. Plasma valine and histidine content were more prevalent in fish fed the control diet than in HFD and HED groups. However, BSA significantly enhanced this content with higher values observed in arginine and alanine content than in control diets at 10 h. Significantly higher liver and plasma Aspartate aminotransferase, Xanthine oxidase, and Glutamate dehydrogenase content were found in the HFD than in the control group. However, the administration of BSA at 10 h improved these parameters similar to the control. Meanwhile, protease, Lipase, aminopeptidase N, carboxypeptidase A, and Na+ K+‐ATPase were influenced significantly (p < 0.001) by sampling time, dietary treatments, and their interaction. Fish fed with the HFD and HED significantly downregulated (p < 0.05) the akt, bcat2, 4e‐bp1, s6k1, and tor expression compared to the control. However, BSA administration at 10 h improved these genes similar to the control. This study indicated that oral BSA administration could benefit plasma amino acid through the TOR signaling pathway in blunt snout bream fed high‐fat and high‐energy diets. [ABSTRACT FROM AUTHOR]

Oral delivery of an inexpensive COVID-19 (coronavirus disease 2019) vaccine could dramatically improve immunization rates, especially in low- and middle-income countries. Previously, we described a potential universal COVID-19 vaccine, rLVS ΔcapB/MN, comprising a replicating bacterial vector, LVS (live vaccine strain) ΔcapB, expressing the highly conserved SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) membrane and nucleocapsid (N) proteins, which, when administered intradermally or intranasally, protects hamsters from severe COVID-19-like disease after high-dose SARS-CoV-2 respiratory challenge. Here, we show that oral administration of the vaccine also protects against high-dose SARS-CoV-2 respiratory challenge; its protection is comparable to that of intradermal, intranasal, or subcutaneous administration. Hamsters were protected against severe weight loss and lung pathology and had reduced oropharyngeal and lung virus titers. Protection against weight loss and histopathology by the vaccine, which in mice induces splenic and lung cell interferon gamma in response to N protein stimulation, was correlated in hamsters with pre-challenge serum anti-N TH1-biased IgG (IgG2/3). Thus, rLVS ΔcapB/MN has potential as an oral universal COVID-19 vaccine. IMPORTANCE The COVID-19 pandemic continues to rage into its fourth year worldwide. To protect the world's population most effectively from severe disease, hospitalization, and death, a vaccine is needed that is resistant to rapidly emerging viral variants of the causative agent SARS-CoV-2, inexpensive to manufacture, store, and transport, and easy to administer. Ideally, such a vaccine would be capable of oral administration, especially in resource-poor countries of the world where there are shortages of needles, syringes and trained personnel to administer injectable vaccines. Here, we show that oral administration of a bacterium-vectored vaccine meeting all these criteria protects naturally susceptible Syrian hamsters from severe COVID-19-like disease, including severe weight loss and lung pathology, after high-dose SARS-CoV-2 respiratory challenge. As the vaccine is based upon inducing immunity to highly conserved SARS-CoV-2 membrane and nucleocapsid proteins, as opposed to the rapidly mutating Spike protein, it should remain resistant to newly emerging SARS-CoV-2 variants.

Abstract The objective was to evaluate the effect of oral administration of strontium (Sr) on the regeneration of a critical bone defect. Twenty Wistar rats were divided into two groups, assessed at 15 and 60 days postoperatively: GSr - oral administration of Sr; and CG - without oral administration of Sr. At 15 and 60 days, blood was collected to measure Sr and calcium (Ca), and the calvaria was removed for histomorphological and histomorphometric analyses. Sr+2 plasmatic concentrations were higher in GSr than in CG. The dosage of Ca+2 showed a small increase in the CG about the GSr. In all evaluated groups, new bone formation was restricted to the edges of the defect, and the residual area was filled with fibrous connective tissue. The oral administration of Sr associated with HA microspheres substituted by the metal, in a concentration of 23 mol%, did not affect the formation of the osteoid matrix.

ABSTRACT: Mucosal vaccination strategies are easier to implement than others in large-scale poultry farming. However, the adjuvants that are approved for veterinary use, which are predominantly aluminum- and oil-emulsion-based adjuvants, are not suitable for mucosal vaccination and carry a risk of adverse reactions. In this study, we engineered a novel Lactobacillus plantarum NC8 strain that co-expresses chicken interleukin-2 (IL-2) and IL-17B, which we designated NC8-ChIL2-17B, and evaluated its potential as an oral immunoadjuvant. The immunomodulatory properties of NC8-ChIL2-17B were evidenced by its ability to activate macrophages and inhibit the proliferation of infectious bronchitis virus (IBV) in vitro. We then confirmed its immunoadjuvant activity in vivo by orally administering NC8-ChIL2-17B along with a commercial IBV vaccine to chicks. The results indicated that NC8-ChIL2-17B enhanced the immune response elicited by the IBV vaccine and increased the levels of IBV-specific IgG and sIgA antibodies produced in response to IBV infection. Additionally, administration of NC8-ChIL2-17B promoted weight gain and beneficially modulated the gut microbiota, resulting in improved chicken performance. These findings suggest that oral administration of NC8-ChIL2-17B is a promising strategy to enhance the immune efficacy of the IBV vaccine in chickens, offering an efficacious alternative adjuvant.

Orismilast is a novel oral phosphodiesterase-4 (PDE4) B/D inhibitor being investigated as a potential treatment for moderate-to-severe psoriasis. To evaluate efficacy and safety of orismilast modified-release formulation in moderate-to-severe psoriasis. This multicenter, randomized (1:1:1:1 to 20, 30, 40 mg orismilast or placebo, twice daily), double-blinded, placebo-controlled, parallel-group, phase 2b, 16-week, dose-ranging study evaluated orismilast in adults with moderate-to-severe plaque psoriasis (NCT05190419). Efficacy end points were analyzed using multiple imputation. Of 202 randomized patients, baseline characteristics were balanced across arms, except greater severe disease proportions for orismilast vs placebo. Orismilast showed significant improvements in the primary end point, percentage change in Psoriasis Area and Severity Index (PASI), from baseline to week 16 (orismilast –52.6% to –63.7% and placebo, –17.3%; all P <.001). Greater proportions receiving orismilast achieved PASI75 (39.5%-49.0%; P <.05) and PASI90 (22.0%-28.3%; P <.05 for 20 and 40 mg) vs placebo (PASI75, 16.5% and PASI90, 8.3%) at week 16. Safety findings were as expected with PDE4 inhibition; dose-dependent tolerability effects observed. Small sample size, disease severity imbalance between groups, limited duration and diversity in study population. Orismilast demonstrated greater efficacy vs placebo and a safety profile in line with PDE4 inhibition. [ABSTRACT FROM AUTHOR]

Janus kinase 1 inhibition may alleviate hidradenitis suppurativa (HS)-associated inflammation and improve symptoms. To assess efficacy and safety of povorcitinib (selective oral Janus kinase 1 inhibitor) in HS. This placebo-controlled phase 2 study randomized patients with HS 1:1:1:1 to receive povorcitinib 15, 45, or 75 mg or placebo for 16 weeks. Primary and key secondary end points were mean change from baseline in abscess and inflammatory nodule count and percentage of patients achieving HS Clinical Response at week 16. Of 209 patients randomized (15 mg, n = 52; 45 mg, n = 52; 75 mg, n = 53; placebo, n = 52), 83.3% completed the 16-week treatment. At week 16, povorcitinib significantly reduced abscess and inflammatory nodule count from baseline (least squares mean [SE] change: 15 mg, –5.2 [0.9], P =.0277; 45 mg, –6.9 [0.9], P =.0006; 75 mg, –6.3 [0.9], P =.0021) versus placebo (–2.5 [0.9]). More povorcitinib-treated patients achieved HS Clinical Response at week 16 (15 mg, 48.1%, P =.0445; 45 mg, 44.2%, P =.0998; 75 mg, 45.3%, P =.0829) versus placebo (28.8%). A total of 60.0% and 65.4% of povorcitinib- and placebo-treated patients had adverse events. Baseline lesion counts were mildly imbalanced between groups. Povorcitinib demonstrated efficacy in HS, with no evidence of increased incidence of adverse events among doses. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis significantly impacts public health, as it causes severe morbidity. Infections caused by Schistosoma mansoni (S. mansoni) can be treated with gold nanoparticles (AuNPs). This study aims to determine the most effective route of AuNPs administration and the magnitude of its anti-fibrotic effect. Methods: In the five groups' in vivo assay design, AuNPs were administered intraperitoneally (1 mg/kg) and orally (1 mg/100 g) to S. mansoni-infected mice. Biochemical parameters (serum levels of albumin and liver enzymes alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured. The histological changes of the liver in distinct groups were evaluated using Hematoxylin and Eosin, Masson's trichrome, and immunohistochemical stains. Results: Infection with S. mansoni was associated with substantial changes in the histological architecture of liver tissue and abnormal levels of hepatic function tests (albumin, AST, and ALT). Schistosoma infected hepatocytes exhibited an abnormal microscopic morphology, granuloma formation and aggressive fibrosis. AuNPs restored the liver histological architecture with a highly significant anti-fibrotic effect and significantly corrected hepatic function test levels. Intraperitoneal administration of AuNPs resulted in the most significant anti-fibrotic effect against hepatic S. mansoni infection as observed in all histological sections with Masson's trichrome being the best stain to represent this fact. Conclusion: For treating S. mansoni-induced chronic liver fibrosis, intraperitoneal administration of AuNPs is a successful and effective route of administration that can be recommended. [ABSTRACT FROM AUTHOR]

Sodium bicarbonate is used as an ergogenic supplement to enhance people's performances in various exercises. This study aimed to evaluate the effects of intestinal delivery of sodium bicarbonate on bicarbonate absorption and associated side effects in an experimental human trial. After preparing and assessing enteric-coated and uncoated sodium bicarbonate tablet formulations, pharmacokinetic analysis and gastrointestinal symptom tests were performed after oral administration in the human body. The dose required to increase blood bicarbonate concentration over 5 mmol∙L−1 for the purpose of improving performance during high-intensity exercise was also determined. Enteric-coated tablet formulation protects sodium bicarbonate under acidic conditions and releases bicarbonate in the intestine. Enteric-coated tablet formulation also reduced the oral dose required to achieve a blood bicarbonate concentration over 5 mmol∙L−1 from 300 mg∙kg−1 of uncoated tablet formulation to 225 mg∙kg−1. Gastrointestinal discomfort was significantly decreased for the group given 225 mg∙kg−1 enteric-coated tablets compared to that given 300 mg∙kg−1 uncoated tablets. These results suggest that enteric-coated tablet formulation could reduce the oral dose required in order to achieve a blood bicarbonate concentration over 5 mmol∙L−1 by 25%, from 300 mg∙kg−1 to 225 mg∙kg−1, along with its ability to reduce gastrointestinal discomfort associated with the dosage. [ABSTRACT FROM AUTHOR]

The oral administration is probably the most used and largely applicable method, even if absorption across the intestinal epithelium is a limiting factor that can invalidate the achievement of a therapy. The aim of this study was to assess the steady state bioavailability of very low molecular weight hyaluronic acid (vLMW-HA) and its distribution in different districts of mice. Adult female C57BL6/J mice (n = 26) were divided in three groups and orally treated for 7 days with: saline solution (SHAM-HA), high dose of vLMW-HA (5 kDa; 500 mg/kg/day; HD-vLMW-HA), and low dose of vLMW-HA (5 kDa; 100 mg/kg/day; LD-vLMW-HA). HA content was quantified in plasma, skin, bladder, gut, rectum, vagina, and eyes with ELISA assay at the end of treatment. HA level significantly increased after treatment with HD-vLMW-HA in all analyzed tissues and plasma. Therefore, vLMW-HA easy absorption and distribution after the oral intake opens new possibilities for future biomedical applications. [ABSTRACT FROM AUTHOR]

Macromolecules are fragile when orally administered. An intestinal villi‐inspired metal–organic frameworks (MOFs)‐based smart pill with multiple advantages is developed to offer a salubrious solution for oral delivery of enzymes. In the pill, MOFs accommodate enzymes as carriers exhibit excellent in vitro and in vivo catalytic activities with good oral biosafety, displaying supreme protection from degradation or inhibition in simulated gastrointestinal tract and high tolerance in simulated gastric acid and intestinal fluid. Moreover, the bioinspired pill possesses the morphology of the small intestinal villi obtained via an in situ moulding strategy for enhancing biocatalysis, which is attributed to the increase of surface area. Collaboratively, the adhesive layer renders increased smart pill in vivo retention, which is verified in pigs, providing a clinically translational and versatile platform for long‐term oral macromolecule delivery. [ABSTRACT FROM AUTHOR]

The perception regarding lactate has changed over the past decades, and some of its physiological roles have gradually been revealed. However, the effects of exogenous lactate on skeletal muscle synthesis remain unclear. This study aimed to confirm the effects of a 5‐week lactate administration and post‐exercise lactate administration on skeletal muscle synthesis. Thirty‐two Institute of Cancer Research mice were randomly assigned to non‐trained + placebo, non‐trained + lactate, trained + placebo, and trained + lactate groups. Furthermore, 3 g/kg of lactate or an equivalent volume of saline was immediately administered after exercise training (maximum oxygen uptake: 70%). Lactate administration and/or exercise training was performed 5 days/week for 5 weeks. After the experimental period, it was observed that lactate administration tended to elevate skeletal muscle weight, increased protein kinase B (p < 0.05) and mammalian target of rapamycin (p < 0.05) mRNA levels, and decreased muscle ring‐finger protein‐1 expression (p < 0.05). Lactate administration after exercise training significantly enhanced plantaris muscle weight; however, it had no additional effects on most signaling factors. This study demonstrated that a 5‐week lactate administration could stimulate skeletal muscle synthesis, and lactate administration after exercise training may provide additional effects, such as increasing skeletal muscle. [ABSTRACT FROM AUTHOR]

The cost of the purification process hinders the extensive use of cytosine phosphate guanosine-oligodeoxynucleotides (CpG-ODNs) for shrimp culture. Therefore, this study used a shuttle vector plasmid to carry 60 copies of CpG-ODN 1668 (pAD43-25_60CpG), which can replicate in Escherichia coli and Bacillus subtilis strain RIK1285. The first experiment used a reverse gavage procedure to deliver a substance (PBS [CK], pAD43-25 [P0], and pAD43-25_60CpG [P60], respectively) directly into the anterior midgut of Penaeus vannamei and transcriptome sequence analysis with a reference genome was performed to examine the expression of well-known immune-related genes. The results showed that the expression levels of immune-related genes in P60 group were significantly increased, particularly those associated with AMPs. In addition, using RT‒qPCR, the expression levels of AMP genes (LvALF, LvPEN-2, and LvPEN-3) in the P60 group may vary depending on the tissue and time point. The second experiment used dietary supplementation with three kinds of heat-killed B. subtilis (HKBS, HKBS-P0, and HKBS-P60) in 28 days of feeding experiments. The results showed that dietary supplementation with HKBS-P60 did not significantly improve shrimp growth performance and survival. However, on days 14 and 28 of the feeding regimens, alkaline phosphatase (AKP) and acid phosphatase (ACP) activity were considerably higher than in other treatments. In addition, following infection with Vibrio harveyi, AKP and ACP activity in the HKBS-P60 group was significantly higher than in other treatments, particularly at the early stage of bacterial infection. Moreover, HKBS-P60 was found to be better protected against V. harveyi infection with lower cumulative mortality (60%) compared to HKBS (90%) and HKBS-P0 (100%) at 7 days after infection. Overall, these findings confirmed that P60 could increase immunological responses in the shrimp midgut, and HKBS-P60 could be used as an effective tool to enhance the immune response and disease resistance in shrimp. [ABSTRACT FROM AUTHOR]

Orally administered compounds represent the great majority of all pharmaceutical compounds produced for human use and are the most popular among patients since they are practical and easy to self-administer. Following ingestion, orally administered drugs begin a "perilous" journey down the gastrointestinal tract and their bioavailability is modulated by numerous factors. The gastrointestinal (GI) tract anatomy can modulate drug bioavailability and accounts for interpatient drug response heterogeneity. Furthermore, host genetics is a contributor to drug bioavailability modulation. Importantly, a component of the GI tract that has been gaining notoriety with regard to drug treatment interactions is the gut microbiota, which shares a two-way interaction with pharmaceutical compounds in that they can be influenced by and are able to influence administered drugs. Overall, orally administered drugs are a patient-friendly treatment option. However, during their journey down the GI tract, there are numerous host factors that can modulate drug bioavailability in a patient-specific manner. [ABSTRACT FROM AUTHOR]

Carvacryl acetate (CA) is a monoterpene obtained from carvacrol, which exhibits anti-inflammatory activity. However, its low solubility in aqueous media limits its application and bioavailability. Herein, we aimed to develop a carvacryl acetate nanoemulsion (CANE) and assess its anti-inflammatory potential in preclinical trials. The optimized nanoemulsion was produced by ultrasound, and stability parameters were characterized for 90 days using dynamic light scattering after hydrophilic–lipophilic balance (HLB) assessment. To evaluate anti-inflammatory activity, a complete Freund's adjuvant-induced inflammation model was established. Paw edema was measured, and local interleukin (IL)-1β levels were quantified using ELISA. Toxicity was assessed based on behavioral changes and biochemical assays. The optimized nanoemulsion contained 3% CA, 9% surfactants (HLB 9), and 88% water and exhibited good stability over 90 days, with no signs of toxicity. The release study revealed that CANE followed zero-order kinetics. Dose–response curves for CA were generated for intraperitoneal and oral administration, demonstrating anti-inflammatory effects by both routes; however, efficacy was lower when administered orally. Furthermore, CANE showed improved anti-inflammatory activity when compared with free oil, particularly when administered orally. Moreover, daily treatment with CANE did not induce behavioral or biochemical alterations. Overall, these findings indicate that nanoemulsification can enhance the anti-inflammatory properties of CA by oral administration. [ABSTRACT FROM AUTHOR]

Chronic osteomyelitis in adults is managed with prolonged courses of intravenous antibiotics in conjunction with surgical debridement of necrotic bone. Over the past 40 years, there has been no paradigm shift in this approach, as randomized controlled trials of this standard of care compared to alternatives such as prolonged oral antibiotics are scarce. However, there have been many small trials, case reports, and review papers evaluating the effectiveness of oral treatment for chronic osteomyelitis. The oral route for infections requiring prolonged treatment is intuitively and practically more favorable due to several advantages, the most important of which is the avoidance of long-term IV antimicrobial therapy with its complications, inconvenience, and cost. In this paper, we review the literature evaluating oral antibiotic therapy in the management of chronic bone infections since 1975. The majority of osteomyelitis infections are caused by Staphylococcus aureus, hence we focus on its treatment using oral antibiotics; however, we also emphasize subpopulations of patients with diabetes, implanted hardware, and with less common bacterial organisms. The primary objective of this review is to promulgate clinical recommendations on the use of oral antibiotics in bone infections in the context of initial therapy, transition from intravenous therapy, and the role of chronic suppression. The secondary objective is to summarize current knowledge of the specific oral antimicrobial agents that are commonly utilized, together with a synopsis of the available literature pertaining to their pharmacokinetic/pharmacodynamic properties and duration of therapy in bone infection. [ABSTRACT FROM AUTHOR]

Cancer vaccines, a burgeoning strategy in cancer treatment, are exploring innovative administration routes to enhance patient and medical staff experiences, as well as immunological outcomes. Among these, oral administration has surfaced as a particularly noteworthy approach, which is attributed to its capacity to ignite both humoral and cellular immune responses at systemic and mucosal tiers, thereby potentially bolstering vaccine efficacy comprehensively and durably. Notwithstanding this, the deployment of vaccines through the oral route in a clinical context is impeded by multifaceted challenges, predominantly stemming from the intricacy of orchestrating effective oral immunogenicity and necessitating strategic navigation through gastrointestinal barriers. Based on the immunogenicity of the gastrointestinal tract, this review critically analyses the challenges and recent advances and provides insights into the future development of oral cancer vaccines. [ABSTRACT FROM AUTHOR]

The montmorillonite-sodium alginate (MMT-SA) colon-targeting microcapsules have been designed as a WGX-50 encapsulation and controlled release vehicle used in oral administration. The MMT-SA microcapsule was formed from a cross-linking reaction, and the stable micropore in the microcapsule changed with a different MMT-SA mixed mass ratio. The MMT-SA microcapsule has a reinforced micropore structure and an enhanced swell–dissolution in SIF and SCF with alkaline environment, which is attributed to the incorporated MMT. The MMT-SA microcapsule exhibited a high WGX-50 encapsulation rate up to 98.81 ± 0.31% and an obvious WGX-50 controlled release in the simulated digestive fluid in vitro. The WGX-50 loaded with MMT-SA microcapsule showed a weak minimizing drug loss in SGF (Simulated Gastric Fluid) with an acidic environment, while it showed a strong maximizing drug release in SIF (Simulated Intestinal Fluid) and SCF (Simulated Colonic Fluid) with an alkaline environment. These features make the MMT-SA microcapsule a nominated vehicle for colon disease treatment used in oral administration. [ABSTRACT FROM AUTHOR]

The aim of this study was to find the effects of oral administration of 17β-estradiol (E2) on growth performance, gonadal development, and spawning performance in zebrafish (Danio rerio). For this purpose, fish (57 dph) were fed for 28 days with three treatments, including: 1) 0 mg E2 kg diet−1 (E0); 2) a low dose of E2 (1 mg E2 kg diet−1, E1); and 3) a high dose of E2 (10 mg E2 kg diet−1, E10). The growth in males and females in the E1 group was significantly higher than the other groups (P < 0.05). Higher and lower feed conversion ratios were found in the E10 and E1 groups, respectively (P < 0.05). Higher oocyte diameters were achieved in the E1 (448.6 ± 57.4 µm) and E10 (404.2 ± 47.5 µm) groups compared with the E0 group (238.9 ± 38.2 µm) (P < 0.05). Histological observations of the gonads indicated that testis in E1 group was more developed compared to the E10 and E0 groups. Moreover, most oocytes in E1 were in the final maturation stage (P < 0.05). Higher and lower hatching rates occurred in the E1 and E10 treatments, respectively (P < 0.05). Additionally, a higher mean number of larvae per brooders and higher mortality rates occurred in the E1 and E10 treatments, respectively (P < 0.05). According to the findings of this study, low doses of E2 improved spawning performance (higher hatching rate) and decreased larval mortalities, while at a high dose, it reduced reproductive performance in zebrafish. Overall, these results proposed 1 mg of E2 kg diet−1 is an effective dose for both male and female zebrafish growth, gonadal development and spawning performance.

The domestic silkworm, Bombyx mori, has been widely used in silk production for centuries. It is also used as a bioreactor by the textile and pharmaceutical industries to mass produce recombinant bioactive proteins containing silk-based materials. Furthermore, silkworms are well-known as a source of food and have also been orally administered to prevent and treat several human disorders. In this study, we aimed to investigate the inherent bio-physicochemical properties of edible silkworms to accurately evaluate their clinical and nutritional potential. We prepared raw powder from whole larvae of silkworm. The yield rate of the powder derived from dried larvae was almost 100% (98.1–99.1% in replicates). As “percentage yield” translates to “Budomari” in Japanese, this raw powder was named “B100rw.” We further prepared B100dn that was denatured through autoclaving. Thereafter, we examined whether B100rw sustained the original bio-physicochemical properties by comparing it with B100dn. There was no significant difference in nutritional content between B100rw and B100dn. B100rw contained proteins derived from silkworm larvae and mulberry leaves, whereas the proteins of B100dn were mostly degraded. On measuring the enzymatic activity of both powders using trehalase as an indicator enzyme, B100rw was found to maintain trehalase activity. B100rw also maintained a random coil conformation, similar to that of liquid silk. This suggested that B100rw sustained the unique bio-physicochemical properties of living larvae. These findings may facilitate the development of novel food products or orally administered vaccines.

Abstract This study investigated the effect of oral bovine serum albumin (BSA) on plasma amino acid profile and growth performance in blunt snout bream fed high‐fat and high‐energy diets. A total of 360 fish (average weight: 45.84 ± 0.07 g) were randomly divided into three groups in four replicates and fed with the control, high‐fat diet (HFD), and high‐energy diet (HED), respectively. After 12 weeks of feeding, fish were orally administered with 10% BSA for 10 h, with the blood and liver sample obtained at 10 h. The results showed no remarkable difference (p > 0.05) in final weight, weight gain rate, feed conversion ratio, protein efficiency ratio, and daily growth rate among dietary treatments. However, fish fed HFD and HED obtained significantly higher energy and nitrogen retention content than the control. Plasma valine and histidine content were more prevalent in fish fed the control diet than in HFD and HED groups. However, BSA significantly enhanced this content with higher values observed in arginine and alanine content than in control diets at 10 h. Significantly higher liver and plasma Aspartate aminotransferase, Xanthine oxidase, and Glutamate dehydrogenase content were found in the HFD than in the control group. However, the administration of BSA at 10 h improved these parameters similar to the control. Meanwhile, protease, Lipase, aminopeptidase N, carboxypeptidase A, and Na+ K+‐ATPase were influenced significantly (p

In recent years, numerous studies have discovered the potential of natural compounds extracted from medicinal plants as a promising alternative treatment for ischemic stroke (IS). Oroxylum indicum is among the plants that has been widely proven to contain a beneficial flavonoid compound known as baicalein. However, the therapeutic potential of this compound for IS disease has yet to be demonstrated. In this study, a baicalein-enriched fraction (BEF) was harvested from the leaves of O. indicum and tested on neural stem cells (NSCs) to determine its effects on the cell viability and gene expression prior to an in vivo animal study. NSCs were chosen because they are the primitive brain cells that play important roles in neurogenesis after IS injury. It was found that NSCs treated with BEF at concentration of 3.125 µg/mL for 48 hours showed a significant higher cell proliferation rate. Moreover, these cells expressed high NSC markers (Nestin and SOX2) and genes responsible for antioxidant (SOD2) and angiogenesis (ANGPT1) mechanisms, indicating that the BEF treatment could enhance the progenitor brain cells viability and the expression of cytokines that are beneficial to reduce oxidative stress and reinstate blood flow in an ischemic brain. Subsequently, the in vivo therapeutic effects of BEF for IS disease was tested by administering 50 mg/kg b.wt of BEF to male Sprague Dawley (SD) rats via oral gavage before and after induction of IS. Assessments of neurological impairments were performed using a modified neurological severity score (mNSS) and the quantification of the total infarct volume was evaluated as the endpoint of this study. Results showed that an oral administration of BEF improved the behavioral scoring for motor functions (forelimb flexion and forelimb twisting), contralateral sensory functions (paw-whiskers test), motor coordination, balance functions (beam balance test) and reflex functions (pinna, corneal, startle and tail reflex) within 24–72 h; alternatively, the non-treated rats showed continuously lower scores for all the tests throughout the study, indicating that the BEF-treated rats exhibited a faster recovery rate as compared to the non-treated rats. Such improvements were observed up to two weeks. In addition, histological assessment also revealed a reduction of infarct volume in the BEF-treated rats as compared to the control rats. In summary, the present study demonstrated the potential of BEF extracted from the O. indicum as a supplement to improve preclinical IS models.

The purpose of the research is to determine main toxicological parameters in repeated intragastric administration of Altric-Extra for veterinary use to laboratory outbred rats.Materials and methods. White outbred rats were used as a test system in the study. The experiment used clinical, toxicological, biochemical and morphological research methods.Results and discussion. Altric-Extra doses of 325 and 650 mg/kg were toxic for the laboratory animals. When administered daily intragastrically to the rats in the above doses, the drug had a negative effect on the functional status of the hemopoietic organs, and excretory and digestive systems. The main target organ for this drug is the thymus. Functional disorders in the above organs and systems are irreversible as evidenced by the post-mortem examination, general blood analysis, and biochemical blood test obtained 10 days after the drug administration was completed.

Oxidative stress is common in several human and veterinary conditions and it is associated to alteration of the glutathione peroxidase (GPx) level. GPx is an enzyme present in erythrocytes, kidney, and liver and it has a role in protecting against oxidative damage. In this randomised double-blinded control trial on healthy dogs, we present findings indicating that the administration for a total of 35 days of a supplement containing S-acetyl-glutathione (SAG) alongside other antioxidant natural ingredients, leads to an increase in the GPx level. Furthermore, the supplement positively changes liver blood parameters, even in healthy dogs. These preliminary results hold promise for conducting new studies using the same supplement on dogs affected by liver conditions, thereby confirming its antioxidant effects and the potential improvement of altered blood parameters.HIGHLIGHTS Oxidative stress characterises several conditions in dogs and the use of antioxidants can improve their health. The administration of a new supplement containing S-acetyl-glutathione (SAG) together with other antioxidant natural ingredients, increased the level of glutathione peroxidase (GPx). No adverse events were reported after the supplement administration.

Three hyperimmune egg-based formulations rich in immunoglobulin Y (IgY) were orally administered (daily, for up to 90 days) to C57BL/6 mice that were not microbially challenged. The serum levels of 32 cytokines were quantified every 30 days. Histopathology, hematology, and serum biochemistry investigations were also performed. As a sign of increased immune activity, lymphohistiocytic infiltrates were detected in the digestive tract and the liver after 30, 60, and 90 days of treatment. These infiltrates were also present in the lungs after 30 and 60 days, but not at 90 days. Blood analysis indicated systemic inflammation after 30 days of treatment: increases in pro-inflammatory cytokines, glycemia, total serum proteins, ALT, and ALP. After 60 and 90 days of treatment, the analyzed blood parameters showed mixed signs of both increased and decreased inflammation. The increased cytokines, which varied with formulation and time of exposure, indicated a combination of mostly Th17- and Th2-type immune responses. As the mice were healthy and housed in standardized sanitary conditions, and were not microbially challenged, the data were consistent with an interaction of IgY with the gut-associated lymphoid tissue as the main mechanism of action. This interaction generated a local immune response, which subsequently induced a systemic response.

The gut microbiota is closely associated with human health, and alterations in gut microbiota can influence various physiological and pathological activities in the human body. Therefore, microbiota regulation has become an important strategy in current disease treatment, albeit facing numerous challenges. Nanomaterials, owing to their excellent protective properties, drug release capabilities, targeting abilities, and good biocompatibility, have been widely developed and utilized in pharmaceuticals and dietary fields. In recent years, significant progress has been made in research on utilizing nanomaterials to assist in regulating gut microbiota for disease intervention. This review explores the latest advancements in the application of nanomaterials for microbiota regulation and offers insights into the future development of nanomaterials in modulating gut microbiota.

Patients with diabetes, the elderly, and those who have certain inherited conditions are particularly vulnerable to atypical wound healing with lingering repercussions. Remarkably, the current remedies are insufficient since, despite the plethora of wound healing options, only limited efficacy is observed. This review is a bibliographic survey on eicosapentaenoic acid and its healing effects. It has been investigated in terms of its source of origin, structure, physico-chemical properties, and studies where healing action is demonstrated. Fatty acids, found in all layers of the skin, modify cell function and the synthesis of eicosanoids, reactive oxygen species, and cytokines, which affects skin structure and immunological condition. As a result, fatty acids influence both the inflammatory response and the wound-healing process. EPA is one of the dietary lipids that has a variety of health advantages. It functions in anti-inflammatory processes and the firmness of cell membranes and is integrated into numerous bodily parts. EPA has a crucial role in healthy fetal development and aging. It is a precursor to numerous metabolites that are powerful lipid mediators and are regarded by many researchers as being helpful in the treatment or prevention of several disorders. EPA supplement is used after surgery to lessen infections, accelerate wound healing, and speed up recovery, although, according to other researchers, the oral administration of omega-3 fatty acids, particularly the DHA and EPA combination, significantly slows down the healing of wounds and disrupts the structure of collagen through several mechanisms. The controversy in the reported literature is discussed and new technologies useful for the improvement of the wound healing process are also reported.

Oxidative stress is common in several human and veterinary conditions and it is associated to alteration of the glutathione peroxidase (GPx) level. GPx is an enzyme present in erythrocytes, kidney, and liver and it has a role in protecting against oxidative damage. In this randomised double-blinded control trial on healthy dogs, we present findings indicating that the administration for a total of 35 days of a supplement containing S-acetyl-glutathione (SAG) alongside other antioxidant natural ingredients, leads to an increase in the GPx level. Furthermore, the supplement positively changes liver blood parameters, even in healthy dogs. These preliminary results hold promise for conducting new studies using the same supplement on dogs affected by liver conditions, thereby confirming its antioxidant effects and the potential improvement of altered blood parameters. Oxidative stress characterises several conditions in dogs and the use of antioxidants can improve their health. The administration of a new supplement containing S-acetyl-glutathione (SAG) together with other antioxidant natural ingredients, increased the level of glutathione peroxidase (GPx). No adverse events were reported after the supplement administration. [ABSTRACT FROM AUTHOR]

Gefitinib (GEF) is a clinical medication for the treatment of lung cancer targeting the epidermal growth factor receptor (EGFR). However, its efficacy is remarkably limited by low solubility and dissolution rates. In this study, two cocrystals of GEF with co-formers were successfully synthesized using the recrystallization method characterized via Powder X-ray Diffraction, Fourier Transform Infrared Spectroscopy, and 2D Nuclear Overhauser Effect Spectroscopy. The solubility and dissolution rates of cocrystals were found to be two times higher than those of free GEF. In vitro cytotoxicity studies revealed that the cocrystals enhanced the inhibition of cell proliferation and apoptosis in A549 and H1299 cells compared to free GEF. In mouse models, GEF@TSBO demonstrated targeted, safe, and effective antitumor activity with only one-dose administration. Mechanistically, the GEF cocrystals were shown to increase the cellular levels of damaged DNA, while potentially downregulating PARP, thereby impairing the DNA repair machinery and leading to an imbalance between DNA damage and restoration. These findings suggest that the cocrystallization of GEF could serve as a promising adjunct to significantly enhance the physicochemical and biopharmaceutical performance for lung cancer treatment, providing a facial strategy to improve GEF anticancer efficiency with high bioavailability that can be orally administrated with only one dose. [ABSTRACT FROM AUTHOR]