Prophylactic Effect Research Articles

Prophylatic use of IV nalmefene to prevent epidural opioid-induced pruritus: A multicenter, randomized clinical trial

Study objectiveThe incidence of pruritus from neuraxial opioids is about 60%. Pruritus causes discomfort and decreases the quality of recovery. This randomized double-blinded clinical trial was aimed to evaluate the prophylactic effects of a single dose IV nalmefene on the incidence and severity of epidural opioid-induced pruritus within 24 h after surgeries. DesignA two-center, randomized, double blinded, controlled clinical trial. SettingThe study was conducted from March 2022 to February 2023 at two tertiary care hospitals in China. PatientsPatients aged between 18 and 80 years-old who underwent elective surgeries and received epidural analgesia intra- and post-operatively were screened for study enrollment. A total of 306 patients were enrolled, 302 patients underwent randomization and 296 patients were included in the final analysis. InterventionsThe nalmefene group was prophylactically given 0.5 μg/kg nalmefene intravenously while the control group was given the same volume of saline. MeasurementsThe primary endpoint was the incidence of pruritus within 24 h after surgeries. The secondary endpoints included time of the first patient-reported pruritus, severity of pruritus after surgeries, severity of acute pain scores after surgeries and other anesthesia/analgesia related side effects. Main resultsPruritus occurred in 51 of the 147 (34.69%) patients in the control group and 35 of the 149 (23.49%) patients in the nalmefene group (odds ratio, 0.58; 95% CI, 0.35 to 0.96; P = 0.034) within 24 h postoperatively. Nalmefene group demonstrated delayed onset of pruritus, reduced severity of pruritus and decreased vomiting within 24 h after surgery. There were no significant differences in postoperative analgesia and the incidence of other anesthesia/analgesia associated side effects. ConclusionsA single dose of 0.5 μg/kg nalmefene intravenously significantly reduced the incidence and severity of epidural-opioid induced pruritus within 24 h after surgery without affecting the efficacy of epidural analgesia.Trial registration: Chinese Clinical Trial Registry (www.chictr.org.cn) and the registration number is ChiCTR2100050463. Registered on August 27th, 2021.

Attenuating RNA Viruses with Expanded Genetic Codes to Evoke Adjustable Immune Response in PylRS-tRNACUAPyl Transgenic Mice.

Ribonucleic acid (RNA) viruses pose heavy burdens on public-health systems. Synthetic biology holds great potential for artificially controlling their replication, a strategy that could be used to attenuate infectious viruses but is still in the exploratory stage. Herein, we used the genetic-code expansion technique to convert Enterovirus 71 (EV71), a prototypical RNA virus, into a controllable EV71 strain carrying the unnatural amino acid (UAA) Nε-2-azidoethyloxycarbonyl-L-lysine (NAEK), which we termed an EV71-NAEK virus. After NAEK supplementation, EV71-NAEK could recapitulate an authentic NAEK time- and dose-dependent infection in vitro, which could serve as a novel method to manipulate virulent viruses in conventional laboratories. We further validated the prophylactic effect of EV71-NAEK in two mouse models. In susceptible parent mice, vaccination with EV71-NAEK elicited a strong immune response and protected their neonatal offspring from lethal challenges similar to that of commercial vaccines. Meanwhile, in transgenic mice harboring a PylRS-tRNACUAPyl pair, substantial elements of genetic-code expansion technology, EV71-NAEK evoked an adjustable neutralizing-antibody response in a strictly external NAEK dose-dependent manner. These findings suggested that EV71-NAEK could be the basis of a feasible immunization program for populations with different levels of immunity. Moreover, we expanded the strategy to generate controllable coxsackieviruses for conceptual verification. In combination, these results could underlie a competent strategy for attenuating viruses and priming the immune system via artificial control, which might be a promising direction for the development of amenable vaccine candidates and be broadly applied to other RNA viruses.

Prophylactic effects of arketamine, but not hallucinogenic psychedelic DOI nor non-hallucinogenic psychedelic analog lisuride, in lipopolysaccharide-treated mice and mice exposed to chronic restrain stress

Anesthetic ketamine and classical psychedelics that act as 5-hydroxytryptamine-2A receptor (5-HT2AR) agonists demonstrated rapid and sustained antidepressant actions in patients with treatment-resistant depression. The new antidepressant arketamine is reported to cause long-lasting prophylactic effects in lipopolysaccharide (LPS)-treated mice and mice exposed to chronic restrain stress (CRS). However, no study has compared the prophylactic effects of DOI (2,5-dimethoxy-4-iodoamphetamine: a hallucinogenic psychedelic drug with potent 5-HT2AR agonism), lisuride (non-hallucinogenic psychedelic analog with 5-HT2AR and 5-HT1AR agonism), and arketamine on depression-like behaviors in mice. Saline (10 ml/kg), DOI (2.0 or 4.0 mg/kg), lisuride (1.0 or 2.0 mg/kg), or arketamine (10 mg/kg) was administered intraperitoneally (i.p.) to male mice 6 days before administration of LPS (1.0 mg/kg). Pretreatment with aketamine, but not DOI and lisuride, significantly ameliorated body weight loss, splenomegaly, the increased immobility time of forced swimming test (FST), and the decreased expression of PSD-95 in the prefrontal cortex (PFC) of LPS-treated mice. In another test, male mice received the same treatment one day before CRS (7 days). Pretreatment with aketamine, but not DOI and lisuride, significantly ameliorated the increased FST immobility time, the reduced sucrose preference in the sucrose preference test, and the decreased expression of PSD-95 in the PFC of CRS-exposed mice. These findings suggest that, unlike to arketamine, both DOI and lisuride did not exhibit long-lasting prophylactic effects in mouse models of depression.

Comparative assessment of identification indicators of the mineral waters of the Nagutsky and Essentuksky deposits by the example of medical and table waters “Nagutskaya‑4” and “Essentuki no. 4

Currently, Russia occupies a leading position in the world in terms of mineral water reserves and the production of packaged mineral drinking water based on them. Identification of food products is one of the modern problems of mankind, which fully applies to packaged mineral water. The article discusses the relevance of developing methodological approaches to the choice of identification indicators of packaged mineral waters. Packaged mineral waters are not only recognized as a food product, but also are a valuable natural balneotherapeutic resource that has a therapeutic and prophylactic effect on the human body. In this regard, the most important task is to develop scientifically based principles and algorithms for determining the geographical origin and authenticity of packaged mineral waters. Currently, the area of traditionally normed indicators of the quality and safety of mineral waters does not imply the possibility of unambiguous identification of products by geographical, natural, and other characteristics. The purpose of this study was to investigate the physicochemical parameters and isotopic characteristics of the mineral water “Nagutskaya — 4” to develop a set of identification indicators. Water quality and compliance with established standards were assessed by organoleptic (transparency, color, taste and smell) and physicochemical (basic composition, mineralization, biologically active components, microcomponents) parameters. Analytical studies of the isotopic characteristics of water were carried out on a Delta V Advantage isotope mass spectrometer with a GasBench II modular set-top box. A list of indicators for the identification of mineral water “Nagutskaya — 4” is proposed, in which, in addition to the main indicators, it is recommended to include fluorides, toxic metals (lithium, strontium, barium) and biologically active components (iodine and bromine), which are typical for this group of waters. It was from the well of the Nagutskoye deposit that packaged water was sold under the brand name “Essentuki No. 4” in the recent past. Therefore, a comparative assessment of the identification indicators of the mineral medicinal table waters “Nagutskaya‑4” and “Essentuki No. 4” was carried out. The results of the assessment showed statistical differences both in the main identification indicators (basic composition, mineralization, biologically active components) and in additional ones (trace components and isotopic characteristics).

The novel immunobiotic Clostridium butyricum S-45-5 displays broad-spectrum antiviral activity in vitro and in vivo by inducing immune modulation.

Clostridium butyricum is known as a probiotic butyric acid bacterium that can improve the intestinal environment. In this study, we isolated a new strain of C. butyricum from infant feces and evaluated its physiological characteristics and antiviral efficacy by modulating the innate immune responses in vitro and in vivo. The isolated C. butyricum S-45-5 showed typical characteristics of C. butyricum including bile acid resistance, antibacterial ability, and growth promotion of various lactic acid bacteria. As an antiviral effect, C. butyricum S-45-5 markedly reduced the replication of influenza A virus (PR8), Newcastle Disease Virus (NDV), and Herpes Simplex Virus (HSV) in RAW264.7 cells in vitro. This suppression can be explained by the induction of antiviral state in cells by the induction of antiviral, IFN-related genes and secretion of IFNs and pro-inflammatory cytokines. In vivo, oral administration of C. butyricum S-45-5 exhibited prophylactic effects on BALB/c mice against fatal doses of highly pathogenic mouse-adapted influenza A subtypes (H1N1, H3N2, and H9N2). Before challenge with influenza virus, C. butyricum S-45-5-treated BALB/c mice showed increased levels of IFN-β, IFN-γ, IL-6, and IL-12 in serum, the small intestine, and bronchoalveolar lavage fluid (BALF), which correlated with observed prophylactic effects. Interestingly, after challenge with influenza virus, C. butyricum S-45-5-treated BALB/c mice showed reduced levels of pro-inflammatory cytokines and relatively higher levels of anti-inflammatory cytokines at day 7 post-infection. Taken together, these findings suggest that C. butyricum S-45-5 plays an antiviral role in vitro and in vivo by inducing an antiviral state and affects immune modulation to alleviate local and systemic inflammatory responses caused by influenza virus infection. Our study provides the beneficial effects of the new C. butyricum S-45-5 with antiviral effects as a probiotic.

Evaluating the radioprotective effect of green barley juice on male rats

Purpose DNA damage accounts for most biological effects of ionizing radiation. Antioxidants are known for their protective effect by preventing DNA damage. This pilot study aimed to evaluate the potential radioprotective effect of Natural SOD®, a green barley juice rich in antioxidants, on DNA damage in the testes and lymphocytes of Wistar rats exposed to ionizing radiation. Materials and methods Male Wistar rats (n = 15) were selected and equally divided into three groups. Rats in one of the groups were pretreated orally with Natural SOD® for 14 days, while rats in another group were sham-pretreated with saline solution. Rats in both these groups were afterwards subjected to a single dose of 6 Gy X-ray whole-body irradiation. The control group did not receive any treatment and was not irradiated. Shortly after X-ray exposure, all rats were sacrificed and testes and blood were collected. Gamma-H2AX and histopathological assessment in the testes, along with comet assay of lymphocytes were performed. Results Histopathological examination of the testes showed no significant architectural alterations. Immunofluorescent staining of γ-H2AX revealed more DNA double-strand break sites in testicular cells from sham animals compared to Natural SOD® pretreated rats. Alkaline comet assay results showed increased DNA damage in lymphocytes of irradiated rats compared to the control group with little differences between the pretreated groups. Animals pretreated with Natural SOD showed slightly reduced DNA damage compared to sham-pretreated rats. These findings suggest a potential protective effect of Natural SOD® against radiation-induced DNA damage. Conclusions Natural SOD® exhibited a potential prophylactic radioprotective effect in rats, particularly in testes. Further investigations to determine medium and long-term effects of X-ray in animals administered Natural SOD® are needed to better estimate the radioprotective effect.

Comparison of Prophylactic Effects between Localized Biomimetic Minocycline and Systematic Amoxicillin on Implants Placed Immediately in Infected Sockets.

This study evaluated the prophylactic effect of localized biomimetic minocycline and systemic amoxicillin on immediate implant placement at infected extraction sites. Twelve mongrels with six implants each were randomly assigned to five groups: uninfected negative control (Group N); infected with oral complex bacteria (Group P); infected and treated with amoxicillin one hour before implant placement (Group A); infected and treated with minocycline during implant placement (Group B); and infected and treated with amoxicillin one hour before implant placement and with minocycline during implant placement (Group C). Radiographic bone level, gingival index (GI), probing depth (PD), papillary bleeding index (PBI), and removal torque (RT) were recorded. There was no significant difference between Groups A, B, and C for bone loss. Group A showed the highest RT, the lowest PBI, and significantly lower GI and PD values than Group P. Group B exhibited significantly higher RT value than Group N and significantly smaller PD value than Group P at 6 w postoperatively. Localized minocycline could improve implant success by reducing bone loss and increasing RT and systemic amoxicillin could maintain the stability of the peri-implant soft tissue. However, combined use of these two antibiotics did not augment the prophylactic effect.

Synergistic Antibiofilm Action of Cinnamomum verum and Brazilian Green Propolis Hydroethanolic Extracts against Multidrug-Resistant Strains of Acinetobacter baumannii and Pseudomonas aeruginosa and Their Biocompatibility on Human Keratinocytes.

The accumulated dental biofilm can be a source of oral bacteria that are aspirated into the lower respiratory tract causing ventilator-associated pneumonia in hospitalized patients. The aim of this study was to evaluate the synergistic antibiofilm action of the produced and phytochemically characterized extracts of Cinnamomum verum and Brazilian green propolis (BGP) hydroethanolic extracts against multidrug-resistant clinical strains of Acinetobacter baumannii and Pseudomonas aeruginosa, in addition to their biocompatibility on human keratinocyte cell lines (HaCaT). For this, High-performance liquid chromatography analysis of the plant extracts was performed; then the minimum inhibitory and minimum bactericidal concentrations of the extracts were determined; and antibiofilm activity was evaluated with MTT assay to prevent biofilm formation and to reduce the mature biofilms. The cytotoxicity of the extracts was verified using the MTT colorimetric test, evaluating the cellular enzymatic activity. The data were analyzed with one-way ANOVA and Tukey's tests as well as Kruskal-Wallis and Dunn's tests, considering a significance level of 5%. It was possible to identify the cinnamic aldehyde in C. verum and p-coumaric, caffeic, and caffeoylquinic acids as well as flavonoids such as kaempferol and kaempferide and Artepillin-C in BGP. The combined extracts were effective in preventing biofilm formation and reducing the mature biofilms of A. baumannii and P. aeruginosa. Moreover, both extracts were biocompatible in different concentrations. Therefore, C. verum and BGP hydroethanolic extracts have bactericidal and antibiofilm action against multidrug resistant strains of A. baumannii and P. aeruginosa. In addition, the combined extracts were capable of expressively inhibiting the formation of A. baumannii and P. aeruginosa biofilms (prophylactic effect) acting similarly to 0.12% chlorhexidine gluconate.

A single-shot prophylactic tumor vaccine enabled by an injectable biomembrane hydrogel.

Prophylactic tumor vaccines hold great promise against tumor occurrence. However, their clinical efficacy remains low due to inadequate activation of strong-sustainable immunity. Herein, a biomembrane hydrogel was designed as a powerful single-shot prophylactic tumor vaccine. Mannose-decorated hybrid biomembrane (MHCM) modified with oxidized sodium alginate (OSA) was designed as a gelator (O-MHCM), where the hybrid biomembrane (HCM) is a hybridization of bacterial outer membrane vesicles (OMV) and tumor cell membranes (TCM). The O-MHCM enables quick gelation subcutaneously where the cysteine protease inhibitor E64 is encapsulated in hydrogel micropores. After a single vaccination of E64@O-MHCM hydrogel, MHCM and E64 are released sustainably due to OSA moiety degradation. The MHCM enables active targeting to dendritic cells (DC) and effective DC maturation. Meanwhile, the E64 enables sufficient antigen availability for subsequent cross presentation. Ultimately, strong and sustainable T lymphocyte-mediated immunity was elicited, demonstrating a strong prophylactic effect against breast tumors. This study provides a long-lasting platform to prevent tumor occurrence, opening an innovative avenue for the design of a single-shot prophylactic tumor vaccine. STATEMENT OF SIGNIFICANCE: Developing a single-shot prophylactic tumor vaccine to elicit strong-sustainable immunity is of great interest clinically. Here, a prophylactic tumor vaccine was designed using an injectable biomembrane hydrogel for achieving strong-sustainable immunity. The mannose-tailored hybrid biomembrane was modified with oxidized sodium alginate to result in a gelator, which enabled the formation of the hydrogel after subcutaneous injection. Cysteine protease inhibitor E64 was incorporated into the micropores of the hydrogel. The hydrogel induced strong-sustainable immunity through the continuous release of active components. This was facilitated by the mannose moiety, which enabled active targeting, as well as the antigen and adjuvant function of biomembrane, and the E64-enabled suppression of antigen degradation. The biomembrane hydrogel demonstrated powerful prevention of 4T1 breast tumors. This study offers an attractive strategy for designing a single-shot prophylactic tumor vaccine.

Prophylactic effect of exogenous melatonin and melatonin receptor agonists on postoperative delirium in elderly patients: a systemic review and meta-analysis of randomized controlled trials.

The prophylactic effect of exogenous melatonin and melatonin receptor agonists (MMRAs) on postoperative delirium (POD) in elderly patients remains controversial. This study aimed to assess the prophylactic effect of MMRAs on POD by conducting a systemic review and meta-analysis of randomized controlled trials (RCTs). We systematically searched four electronic databases including PubMed, Web of Science, Cochrane Library, and Embase for the eligible studies up to February 28, 2023. The Cochrane risk of bias tool was used for assessing the risk of bias in the included RCTs. The occurrence of POD was the primary outcome. The quality of evidence was evaluated by Grading of Recommendations Assessment, Development, and Evaluation. A total of 11 RCTs comprising patients (MMRA group: 777 patients and placebo group: 781 patients) were included. The results of the meta-analysis showed that the MMRA group had a lower occurrence of POD than the placebo group (risk ratio = 0.70, 95% confidence interval: 0.51-0.97, P < 0.05, I2 = 59%). The subgroup analysis showed that melatonin significantly reduced the occurrence of POD (moderate-quality evidence), whereas ramelteon and tryptophan had no significant impact (moderate-quality evidence). Existing evidence suggested that perioperative use of melatonin can prevent POD in elderly patients.

The features of the prevention of preeclampsia in pregnant women with gestational endotheliopathy in the first trimester

The objective: to evaluate the clinical effectiveness of L-arginine in the prevention of preeclampsia and reduction of other perinatal risks in patients with preclinical gestational endotheliopathy (GE).Materials and methods. A comparative clinical study was performed at the clinical base of the Department of Obstetrics and Gynecology N. 1 of the Vinnytsya National Pirogov Memorial Medical University. 116 pregnant women with preclinical GE (main group), which was diagnosed by laboratory and instrumental research (microalbuminuria and endothelium-dependent vasodilatation), took part in the study. The patients of the main group were divided into clinical subgroups: 31 pregnant women with GE in subgroup A received acetylsalicylic acid (ASA) at a dose of 75 mg per or per day; 33 patients with preclinical GE from subgroup B received L-arginine at a dose of 4-4.2 g per or per day; 52 pregnant women with preclinical GE who refused prophylactic treatment were included in the subgroup C. The control group involved 58 pregnant women with a physiological gestation and without GE.The clinical effectiveness of the therapy was assessed by comparing the number of cases of perinatal pathology in the I, II and III trimesters.Results. The use of L-arginine as an alternative preventive therapy for the development of preeclampsia and other perinatal pathology made possible to reduce the rate of preeclampsia significantly (RR 0.19, 95% CI: 0.05-0.77; p=0.02) and placental hyperplasia/hypoplasia (RR 0.17, 95% CI: 0.04-0.68; p=0.01), compared to patients who did not receive any preventive treatment. In pregnant women with early-onset gestational endotheliopathy who received L-arginine, placental dysfunction was not diagnosed in the II and III trimesters of pregnancy and there were no cases of fetal growth retardation. The use of L-arginine was not associated with side effects and/or adverse reactions in the proposed dose and frequency of administration and can be considered beneficial for the mother and the fetus.Conclusions. Prescribing ASA and L-arginine drugs for pregnant women with a moderate degree of perinatal risk (preclinical GE) made possible not only to prolong pregnancy, but also to prevent the development of severe perinatal pathology. A more pronounced clinical effectiveness of the course prescription of solution of L-arginine per or (daily dose of L-arginine - 4.0-4.2 g) in pregnant women with preclinical form of GE may be associated with the endotheliotropic protective effect of the drug.The appropriateness of using L-arginine during pregnancy is still debated, and further researches are needed to determine the optimal dosage, initial period for using and duration for the best prophylactic or therapeutic effect.

Evaluating Prophylactic Effect of Bovine Colostrum on Intestinal Barrier Function in Zonulin Transgenic Mice: A Transcriptomic Study.

The intestinal barrier comprises a single layer of epithelial cells tightly joined to form a physical barrier. Disruption or compromise of the intestinal barrier can lead to the inadvertent activation of immune cells, potentially causing an increased risk of chronic inflammation in various tissues. Recent research has suggested that specific dietary components may influence the function of the intestinal barrier, potentially offering a means to prevent or mitigate inflammatory disorders. However, the precise mechanism underlying these effects remains unclear. Bovine colostrum (BC), the first milk from cows after calving, is a natural source of nutrients with immunomodulatory, anti-inflammatory, and gut-barrier fortifying properties. This novel study sought to investigate the transcriptome in BC-treated Zonulin transgenic mice (Ztm), characterized by dysbiotic microbiota, intestinal hyperpermeability, and mild hyperactivity, applying RNA sequencing. Seventy-five tissue samples from the duodenum, colon, and brain of Ztm and wild-type (WT) mice were dissected, processed, and RNA sequenced. The expression profiles were analyzed and integrated to identify differentially expressed genes (DEGs) and differentially expressed transcripts (DETs). These were then further examined using bioinformatics tools. RNA-seq analysis identified 1298 DEGs and 20,952 DETs in the paired (Ztm treatment vs. Ztm control) and reference (WT controls) groups. Of these, 733 DEGs and 10,476 DETs were upregulated, while 565 DEGs and 6097 DETs were downregulated. BC-treated Ztm female mice showed significant upregulation of cingulin (Cgn) and claudin 12 (Cldn12) duodenum and protein interactions, as well as molecular pathways and interactions pertaining to tight junctions, while BC-treated Ztm males displayed an upregulation of transcripts like occludin (Ocln) and Rho/Rac guanine nucleotide exchange factor 2 (Arhgf2) and cellular structures and interfaces, protein-protein interactions, and organization and response mechanisms. This comprehensive analysis reveals the influence of BC treatment on tight junctions (TJs) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway gene expressions. The present study is the first to analyze intestinal and brain samples from BC-treated Ztm mice applying high-throughput RNA sequencing. This study revealed molecular interaction in intestinal barrier function and identified hub genes and their functional pathways and biological processes in response to BC treatment in Ztm mice. Further research is needed to validate these findings and explore their implications for dietary interventions aimed at improving intestinal barrier integrity and function. The MGH Institutional Animal Care and Use Committee authorized the animal study (2013N000013).

A Randomized Standard-of-Care Controlled Trial of Xenogeneic Platelet-Rich Plasma Lotion to Reduce Acute Radiation Dermatitis in Breast Cancer Patients

Breast cancer patients experience acute radiation dermatitis (ARD) during radiation therapy (RT). The Multinational Association for Supportive Cancer Care published clinical practice guidelines for the prevention and treatment of ARD in 2013, and mild bathing at the irradiated site is the standard health education. This study examined the prophylactic effect of the newly developed xenogeneic platelet-rich plasma (PRP) lotion on acute radiation dermatitis (ARD) for breast cancer patients. Ductal carcinoma in situ and early-stage breast cancers were enrolled after breast conserving surgery. Hypo-fractionated whole breast irradiation (42.5 Gy in 16 fractions) followed by tumor bed boost (10 Gy in 5 fractions) was used. Patients were randomly assigned to the Standard of Care (SOC) group (n = 48) or the PRP lotion group (n = 52). In both groups, patients were educated with standard health education on topical skin care. In the PRP lotion group, patients were instructed to apply the provided lotion twice a day, starting from the first day of RT: the first application within 1 hour after the daily RT session, the second at bedtime, and continue during the weekends. Patients were instructed not to apply the lotion within 6 hours before daily RT. We recorded the following skin reaction every week during RT and two weeks after RT: ARD was graded following the RTOG definition by two radiation oncologists; Dermatology Life Quality Index (DLQI) and Visual Analogue Scale for Pain (VAS Pain) were subjectively scored by patients to present patient-reported outcomes. The statistical software was used for all statistical analyses. The patient characteristics in both groups were balanced except for a higher body mass index in the PRP lotion group. One patient did not complete RT in the SOC group due to pain intolerance. The severity of ARD grading in both groups is shown in Table. In comparison to the SOC group, the PRP lotion group demonstrated significantly reduced and delayed progression of ARD (p<0.01) and VAS Pain (p<0.01) during the whole RT course and two weeks after RT. The DLQI significantly improved at the 2nd week (p = 0.003), 3rd week (p = 0.01), 4th week (p<0.001), and the two weeks post-RT (p<0.001) period; however, this was not observed during the 1st week (p = 0.68). Similarly, the DLQI value progressively worsened two weeks after RT in the SOC group but not in the PRP lotion group. This is the first study to use xenogeneic PRP lotion to prevent ARD clinically. The outcome of this study validated the prophylactic effects of xenogeneic PRP lotion on ARD, subsequently leading to an improved quality of life across the RT course.

Prophylactic effects of dietary caper (Capparis spinosa) extracts on the control of Streptococcus agalactiae infection, growth, immune-antioxidant, and inflammation cytokine responses of Nile tilapia fingerlings

The antibacterial activity of aqueous (AE) or ethanolic extracts (EE) of caper (Capparis spinosa) against Streptococcus agalactiae was evaluated in vitro. Both caper extracts showed antagonistic activity against S. agalactiae and the inhibition zones in case of ethanolic extracts were larger than those of aqueous ones. Additionally, TEM investigations show that S. agalactiae cells treated with both C. spinosa extracts were damaged and degraded and this damage was greater in case of ethanolic extract. Another study was done to assess the promotion effects of dietary caper (C. spinosa) extracts on growth, antioxidant and immune activity, and inflammation cytokine responses of Nile tilapia (Oreochromis niloticus) and its resistance to S. agalactiae infection. However, fish (40 ± 2 g) were fed on diets containing 1.0 and 2.0 g/kg feed of each caper extract as well as the control group (free of caper) for 6 weeks. Fish were intraperitoneally injected (IP) with Streptococcus agalactiae at the end of the feeding trial, and fish mortality was tracked for additional ten days. Compared with other treatments, fish fed on 2.0 g EE/kg feed had higher counts of white and red blood cells as well as higher hemoglobin levels accompanied with lower AST and ALT activities. Antioxidant (superoxide dismutase and catalase activities) and immune, total protein, globulin, lysozyme, and immunoglobulin M) indices were increased along with significant decline in MDA levels in both caper extracts treated fish groups compared to the control group. Significant promotion in fish growth was affected positively with the increase in both caper extracts; particularly, the larger fish growth was observed in the treatment of 2.0 g EE/kg feed. Expressions of IL-1β and IL-8 were declined; meanwhile levels of IL-10, SOD and CAT genes were upregulated in fish fed on 2.0 g EE/kg feed compared to other groups. After being challenged with S. agalactiae infection, fish survival was considerably (P < 0.05) greater in fish groups that fed on diets with caper extracts; particularly 2.0 g EE/kg feed (75%); while all fish fed on the control one were dead. According to these findings, the antioxidant and immune response of Nile tilapia fingerlings is stimulated by ethanolic extract of caper (2.0 g/kg feed), which also enhanced the growth performance and fish resistance to S. agalactiae infection.

Valproic acid treatment attenuates cisplatin-induced kidney injury by suppressing proximal tubular cell damage.

Cisplatin treatment is effective against several types of carcinomas. However, it frequently leads to kidney injury, which warrants effective prevention methods. Sodium valproic acid is a prophylactic drug candidate with a high potential for clinical application against cisplatin-induced kidney injury. Therefore, in this study, we aimed to elucidate the mechanism underlying the prophylactic effect of valproic acid on cisplatin-induced kidney injury in a mouse model and HK2 and PODO cells with cisplatin-induced toxicity. In the mouse model of cisplatin-induced kidney injury, various renal function parameters and tubular damage scores were worsened by cisplatin, but they were significantly improved upon combination with valproic acid. No difference was observed in cisplatin accumulation between the cisplatin-treated and valproic acid-treated groups in whole blood and the kidneys. The mRNA expression levels of proximal tubular damage markers, apoptosis markers, and inflammatory cytokines significantly increased in the cisplatin group 72 h after cisplatin administration but significantly decreased upon combination with valproic acid. In HK2 cells, a human proximal tubular cell line, the cisplatin-induced decrease in cell viability was significantly suppressed by co-treatment with valproic acid. Valproic acid may inhibit cisplatin-induced kidney injury by suppressing apoptosis, inflammatory responses, and glomerular damage throughout the kidneys by suppressing proximal tubular cell damage. However, prospective controlled trials need to evaluate these findings before their practical application.

Catechin hydrate ameliorates cerulein‑induced chronic pancreatitis via the inactivation of TGF‑β/Smad2 signaling.

Chronic pancreatitis (CP) is a pancreatic inflammatory disease associated with histological changes, including fibrosis, acinar cell loss and immune cell infiltration, and leads to damage of the pancreas, which results in pain, weight loss and loss of pancreas function. Catechin or catechin hydrate (CH) has antioxidant, anticancer and immune‑regulatory effects. However, unlike other catechins, the antifibrotic effects of (+)‑CH have not been widely studied in many diseases, including CP. Therefore, the anti‑fibrotic effects of (+)‑CH against CP were evaluated in the present study. To assess the prophylactic effects of CH, (+)‑CH (1, 5 or 10mg/kg) or ethanol was administered 1h before first cerulein (50µg/kg) injection. To assess the therapeutic effects, (+)‑CH (5mg/kg) or ethanol was administered after cerulein injection for one or two weeks. In both methods, cerulein was injected intraperitoneally into mice once every hour, six times a day, four times a week, for a total of three weeks, to induce CP. The data showed that (+)‑CH markedly inhibited glandular destruction and inflammation during CP. Moreover, (+)‑CH prevented pancreatic stellate cell (PSC) activation and the production of extracellular matrix components, such as fibronectin 1 and collagens, which suggested that it may act as a novel therapeutic agent. Furthermore, the mechanism and effectiveness of (+)‑CH on pancreatic fibrosis were investigated in isolated PSCs. (+)‑CH suppressed the activation of Smad2 and fibrosis factors that act through transforming growth factor‑β (TGF‑β) or platelet‑derived growth factor. These findings suggest that (+)‑CH exhibits antifibrotic effects in cerulein‑induced CP by inactivating TGF‑β/Smad2 signaling.

EGb 761 reduces Ca2+ influx and apoptosis after pentylenetetrazole treatment in a neuroblastoma cell line.

Transient receptor potential (TRP) channels have been found to have significant implications in neuronal outgrowth, survival, inflammatory neurogenic pain, and various epileptogenic processes. Moreover, there is a growing body of evidence indicating that transient receptor potential (TRP) channels have a significant impact on epilepsy and its drug-resistant subtypes. We postulated that EGb 761 would modulate TRPA1 channels, thereby exhibiting anti-inflammatory and neuroprotective effects in a neuroblastoma cell line. Our rationale was to investigate the impact of EGb 761 in a controlled model of pentylenetetrazole-induced generalized epilepsy. We evaluated the neuroprotective, antioxidant and anti-apoptotic effects of EGb 761 both before and after the pentylenetetrazole application in a neuroblastoma cell line. Specifically, we focused on the effects of EGB 761 on the activity of Transient receptor potential (TRP) channels. EGb 761 applications both before and after the pentylenetetrazole incubation period reduced Ca release and restored apoptosis, ROS changes, mitochondrial depolarization and caspase levels, suggesting a prominent prophylactic and therapeutic effect of EGb 761 in the pentylenetetrazole-induced epileptogenesis process. Our basic mechanistic framework for elucidating the pathophysiological significance of fundamental ion mechanisms in a pentylenetetrazole treated neuroblastoma cell line provided compelling evidence for the favorable efficacy and safety profile of Egb 761 in human-relevant in vitro model of epilepsy. To the best of our knowledge, this is the first study to investigate the combined effects of EGb 761 and pentylenetetrazole on TRP channels and measure their activation level in a relevant model of human epileptic diseases.

Antidepressant-like effects of tomatidine and tomatine, steroidal alkaloids from unripe tomatoes, via activation of mTORC1 in the medial prefrontal cortex in lipopolysaccharide-induced depression model mice

ABSTRACT Ketamine, an N-methyl-D-aspartate receptor antagonist, produces rapid antidepressant effects in patients with treatment-resistant depression. However, owing to the undesirable adverse effects of ketamine, there is an urgent need for developing safer and more effective prophylactic and therapeutic interventions for depression. Preclinical studies have demonstrated that activation of the mechanistic target of rapamycin complex 1 (mTORC1) in the medial prefrontal cortex (mPFC) mediates the rapid antidepressant effects of ketamine. The steroidal alkaloid tomatidine and its glycoside α-tomatine (tomatine) can activate mTORC1 signaling in peripheral tissues/cells. We examined whether tomatidine and tomatine exerted prophylactic and therapeutic antidepressant-like actions via mPFC mTORC1 activation using a mouse model of lipopolysaccharide (LPS)-induced depression. Male mice were intraperitoneally (i.p.) administered tomatidine/tomatine before and after the LPS challenge to test their prophylactic and therapeutic effects, respectively. LPS-induced depression-like behaviors in the tail suspension test (TST) and forced swim test (FST) were significantly reversed by prophylactic and therapeutic tomatidine/tomatine administration. LPS-induced anhedonia in the female urine sniffing test was reversed by prophylactic, but not therapeutic, injection of tomatidine, and by prophylactic and therapeutic administration of tomatine. Intra-mPFC infusion of rapamycin, an mTORC1 inhibitor, blocked the prophylactic and therapeutic antidepressant-like effects of tomatidine/tomatine in TST and FST. Moreover, both tomatidine and tomatine produced antidepressant-like effects in ovariectomized female mice, a model of menopause-associated depression. These results indicate that tomatidine and tomatine exert prophylactic and therapeutic antidepressant-like effects via mTORC1 activation in the mPFC and suggest these compounds as promising candidates for novel prophylactic and therapeutic agents for depression.

Mineral waters from Spring 1 and Spring 1 bis from Slănic Moldova - molecular mechanisms responsible for triggering the prophylactic and therapeutic effects

In this study, we investigated mineral water's therapeutic and prophylactic effects from springs 1 and 1 bis in Slanic Moldova, focusing on identifying the molecular mechanisms responsible for these effects. We collected water samples from these springs and analyzed their chemical composition using various analytical techniques. In addition, we tested the effects of water on cell viability using primary fibroblasts in culture and performed MTT assays to assess the metabolic activity of the cells. Our results indicate that water from both springs has beneficial properties on cells, including improving cell viability and stimulating metabolic activity. This suggests that the mineral water from springs 1 and 1 bis could have therapeutic and prophylactic potential due to its unique chemical composition. Our study could contribute to developing new mineral water-based therapies for various health conditions.

Effects of ursodeoxycholic acid and glutathione combination in spleen TNF-α and apoptotic index in rats with cholestasis

Background: Cholestasis is a disorder of the formation or flow of bile. Among its contributors, tumour necrosis factor (TNF)-α stands out as the most influential inducer of apoptosis. Meanwhile, ursodeoxycholic acid (UDCA) is a valuable agent with choleretic properties, protecting the hepatobiliary system. Glutathione (GSH) enhances endothelial response and prevents liver fibrosisObjectives: This study evaluates the effect of a combination of GSH-UDCA on splenic TNF-α expression and apoptosis index in Sprague Dawley (SD) rats with cholestasisMethods: This experiment with a post-tests-only control group design involving 28 male SD rats. They were randomly into four groups: group (K) with 20 mg UDCA, group 1 (P1) with 10 mg UDCA + 10 mg GSH, group 2 (P2) was given UDCA 20 mg + GSH 15 mg, and group 3 (P3) was given UDCA 30 mg + GSH 20 mg. Cholestasis was obtained by ligation of the common bile duct through a laparotomy. During three weeks of trial, rats were administered daily with UDCA orally and GSH intramuscularly. On day 22, rats were sacrificed and spleen samples were taken for anatomical pathology examination. Results: There were significant differences in TNF-α expression between groups K vs P3; P1 vs P3, and P2 vs P3 (p=0.002). There was a significant difference in the apoptotic index between groups K vs P1 (p&lt;0.001); K vs P2 (p=0.004), and K vs P3 (p=0.005).Conclusions: The UDCA-GSH combination demonstrated a prophylactic effect in SD rats with cholestasis and might be an effective supplemental therapy with UDCA for cholestatic diseases. The difference in TNF-α expression and apoptotic index was lower in SD rats UDCA-glutathione combination group than single dose UDCA. Between TNF-α and the apoptotic index, there is a moderate positive relation.