Negative Control Treatment Groups Research Articles

Evaluation of the Protective and Healing Effects of Heracleum lasiopetalum Boiss on a Modified Acetic Acid-Induced Ulcerative Colitis Model in Rats

Background: Ulcerative colitis (UC), a chronic inflammatory condition of the colon with no definitive cure, necessitates the exploration of innovative therapies. Herbal remedies combined with conventional drugs may offer complementary benefits, enhancing treatment outcomes. Objectives: This study investigates the therapeutic effects of Heracleum lasiopetalum Boiss in a rat model of acetic acid-induced UC. Methods: Forty-eight adult female Wistar rats were randomly allocated to six groups (n = 8 per group) for each of two experiments. UC was induced by intracolonic administration of 1 ml of 4% acetic acid for 10 minutes. In the treatment groups, female rats received an oral gavage of 5%, 10%, and 40% aqueous plant extract, sulfasalazine (100 mg/kg), and distilled water for 6 days, starting 3 days after acetic acid administration. The protective groups received substances via oral gavage from 7 days before to 3 days after acetic acid administration. The extent of mucosal ulcers, hyperemia, inflammation, and mucosal bleeding was evaluated based on the Gerald Classification System Score (Macroscopic). Pathological assessment was conducted on prepared slides using the modified Wallace method (Microscopic). Changes in body and colon weight, along with food and water intake, were examined. Results: Significant changes in food intake were observed in both the extract and positive control treatment groups, exhibiting a notable difference compared to the negative control group (P < 0.05). Body weight changes experienced a significant increase in the positive control treatment group compared to the negative control group (P < 0.05), while no significant difference was evident between the extract and negative control treatment groups (P > 0.05). In terms of water and food intake, as well as weight changes, no significant differences were detected among the various protective groups (P > 0.05). Both microscopic and macroscopic examinations revealed a substantial enhancement in the colon of the extract and positive control treatment groups compared to the negative control group (P < 0.05), with no significant difference observed between the protective groups (P > 0.05). Conclusions: Heracleum lasiopetalum extract demonstrates a dose-dependent reduction in colon hyperemia, mucosal ulceration, inflammation, and fibrosis. This highlights its potential as a supplementary treatment option for UC, emphasizing the need for further investigation.

Necrosis Description of Mice Liver Induced with Monosodium Glutamate and Methanol Robusta Coffee Bean Extract (Coffea canephora)

This study aimed to analyze the effect of methanol robusta coffee bean extract (Coffea canephora) on liver histopathological description in mice induced with monosodium glutamate (MSG). This study was used 20 male mice for 5 treatment groups: K + (MSG 0.12 mg and Vitamin C 6 mg), K- (MSG 0.12 mg and CMC Na 0.1 ml), P1 (MSG 0.12 mg and RCE 0.1 mg), P2 (MSG 0.12 mg and RCE 0.2 mg), and P3 (MSG 0.12 mg and RCE 0.4 mg) per orally for 42 days. Liver histological scores were analyzed using Kruskal Wallis test. The results of Kruskal Wallis test scored p=0,391 which indicates that the data is not significant (p>0.05). In the control and treatment groups there were no significant. In conclusion, the giving methanol robusta coffee bean extract did not show a decrease in hepatosite damage that was different from the negative control treatment group.

Spray dried smectite clay particles as a novel treatment against obesity

To explore the feasibility of spray dried smectite clay particles fabricated from montmorillonite or laponite materials for adsorbing dietary lipids and reducing rodent weight gain in vivo. Spray dried montmorillonite (SD-MMT) and spray dried laponite (SD-LAP) particles were prepared via spray drying. Particle morphology, surface area and redispersion/aggregation properties in aqueous media were characterized. The ability of SD-MMT and SD-LAP particles to inhibit lipid digestion kinetics and adsorb lipid species from solution was assessed during in vitro lipolysis using proton nuclear magnetic resonance analysis. SD-MMT and SD-LAP particles were dosed to rodents fed a high-fat diet and their effect on body weight gain was evaluated. Both SD-MMT and SD-LAP particles adsorbed significant quantities of medium chain triglycerides and lipolytic products from solution during in vitro lipolysis. At a concentration of 50% w/w relative to lipid content, SD-MMT and SD-LAP particles adsorbed 42% and 94% of all lipid species, respectively. SD-MMT and SD-LAP particles also reduced the extent of rodent weight gain relative to the negative control treatment group and performed similarly to orlistat via an alternate mechanism of action. Spray dried smectite clay particles (SD-MMT and SD-LAP) with significant adsorptive capacities for dietary lipids and digestion products were successfully fabricated. These particles may be developed as novel anti-obesity treatments with fewer adverse effects than currently marketed treatment options.

Effects of Feeding Different Postbiotics Produced by Lactobacillus plantarum on Growth Performance, Carcass Yield, Intestinal Morphology, Gut Microbiota Composition, Immune Status, and Growth Gene Expression in Broilers under Heat Stress.

Simple SummaryHeat stress is a serious issue in commercial broiler production in hot and humid countries, including Malaysia. Exposure of broilers to heat stress affects their health and productivity. In this context, antibiotics are widely used at sub-therapeutic levels as growth promoters to reduce stress and infectious diseases in order to sustain productivity in commercial broiler farms. However, the extensive use of antibiotics as growth promoters for a long time leads to the development of antibiotic-resistant bacteria and the possibility of antibiotic-resistant genes being transferred among organisms. Recently, postbiotics produced by Lactobacillus plantarum have been widely studied as a feed additive in order to replace in-feed antibiotics. However, to date, no studies have investigated the role of postbiotics in feed for broilers under heat stress.The effects of feeding different postbiotics on growth performance, carcass yield, intestinal morphology, gut microbiota, immune status, and growth hormone receptor (GHR) and insulin-like growth factor 1 (IGF-1) gene expression in broilers under heat stress were assessed in this study. A total of 252 one-day-old male broiler chicks (Cobb 500) were randomly assigned in cages in identical environmentally controlled chambers. During the starter period from 1 to 21 days, all the birds were fed the same basal diet. On day 22, the birds were weighed and randomly divided into six treatment groups and exposed to cyclic high temperature at 36 ± 1 °C for 3 h per day from 11:00 to 14:00 until the end of the experiment. From day 22 to 42 (finisher period), an equal number of birds were subjected to one of the following diets: NC (negative control) basal diet; PC (positive control) basal diet + 0.02% oxytetracycline; or AA (ascorbic acid) basal diet + 0.02% ascorbic acid. The other three groups (RI11, RS5 and UL4) were basal diet + 0.3% different postbiotics (produced from different Lactobacillus plantarum strains, and defined as RI11, RS5 and UL4, respectively). The results demonstrated that birds fed RI11 diets had significantly higher final body weight, total weight gain and average daily gain than the birds that received the NC, PC and AA treatments. The feed conversion ratio was significantly higher in the RI11 group compared with the other groups. Carcass parameters were not affected by the postbiotic-supplemented diet. Postbiotic supplementation improved villi height significantly in the duodenum, jejunum and ileum compared to the NC, PC and AA treatments. The crypt depth of the duodenum and ileum was significantly higher in NC group compared to other treatment groups except RI11 in duodenum, and UL4 in ileum was not different with NC groups. The villus height to crypt depth ratio of duodenum and ileum was significantly higher for the postbiotic treatment groups and AA than the PC and NC treatment groups. The postbiotic RI11 group recorded significantly higher caecum total bacteria and Lactobacillus count and lower Salmonella count compared to the NC and PC treatment groups. The Bifidobacterium population in the NC group was significantly lower compared to the other treatment groups. The postbiotic (RI11, RS5 and UL4) and AA treatment groups showed lower Enterobacteriaceae and E. coli counts and caecal pH than the NC and PC treatment groups. The plasma immunoglobulin M (IgM) level was significantly higher in the birds receiving postbiotic RI11 than those receiving other treatments. The plasma immunoglobulin G (IgG) level was higher in the RI11 treatment group than in the NC, AA and RS5 groups. The plasma immunoglobulin A (IgA) level was not affected by postbiotic supplements. The hepatic GHR mRNA expression level was significantly increased in birds fed postbiotics RI11, RS5 and UL4, AA and PC compared to the NC-fed birds. Postbiotic RI11 led to significantly higher hepatic IGF-1 mRNA expression level compared to the NC, PC, and AA treatments. Mortality was numerically lesser in the postbiotic treatment groups, but not significantly different among all the treatments. In conclusion, among the postbiotics applied in the current study as compared with NC, PC and AA, RI11 could be used as a potential alternative antibiotic growth promoter and anti-stress treatment in the poultry industry.

Spray Dried Smectite Clay Particles as a Novel Treatment against Obesity.

To explore the feasibility of spray dried smectite clay particles fabricated from montmorillonite or laponite materials for adsorbing dietary lipids and reducing rodent weight gain in vivo. Spray dried montmorillonite (SD-MMT) and spray dried laponite (SD-LAP) particles were prepared via spray drying. Particle morphology, surface area and redispersion/aggregation properties in aqueous media were characterized. The ability of SD-MMT and SD-LAP particles to inhibit lipid digestion kinetics and adsorb lipid species from solution was assessed during in vitro lipolysis using proton nuclear magnetic resonance analysis. SD-MMT and SD-LAP particles were dosed to rodents fed a high-fat diet and their effect on body weight gain was evaluated. Both SD-MMT and SD-LAP particles adsorbed significant quantities of medium chain triglycerides and lipolytic products from solution during in vitro lipolysis. At a concentration of 50% w/w relative to lipid content, SD-MMT and SD-LAP particles adsorbed 42% and 94% of all lipid species, respectively. SD-MMT and SD-LAP particles also reduced the extent of rodent weight gain relative to the negative control treatment group and performed similarly to orlistat via an alternate mechanism of action. Spray dried smectite clay particles (SD-MMT and SD-LAP) with significant adsorptive capacities for dietary lipids and digestion products were successfully fabricated. These particles may be developed as novel anti-obesity treatments with fewer adverse effects than currently marketed treatment options.

MicroRNA‑195 is associated with regulating the pathophysiologic process of human laryngeal squamous cell carcinoma.

MicroRNAs (miRNAs) have been reported to be associated with the modulation of tumor development, including alterations associated with the development of human laryngeal squamous cell carcinoma (LSCC). The present study was designed to investigate whether miRNA‑195 was associated with the pathophysiologic process of human LSCC and to identify its potential roles and underlying molecular mechanisms. To determine whether miRNA‑195 serves a role in LSCC, reverse transcription‑quantitative polymerase chain reaction was used to detect miRNA‑195 expression in LSCC tissues. The tumor‑suppressive effect of miRNA‑195 was determined by invitro assays. Gain‑of‑function studies using miRNA‑195 mimics were performed to investigate cell viability, migration and invasion, and apoptosis in the AMC‑HN‑8 cell line. Western blotting was performed to reveal the molecular mechanisms of miRNA‑195 and its downstream signaling pathways in the LSCC AMC‑HN‑8 cell line. The present study demonstrated that miRNA‑195 is downregulated in primary LSCC tumors. Upregulating miRNA‑195 invitro suppressed cell viability, migration and invasion in AMC‑HN‑8 cells. Overexpression of miRNA‑195 alone in AMC‑HN‑8 cells was sufficient to induce cell apoptosis, as identified by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Compared with the high expression of miRNA‑195 in AMC‑HN‑8 cells, the expression levels of vascular endothelial growth factor receptor‑II protein and downstream signaling pathway proteins, which were associated with cell viability, migration, invasion and apoptosis, were markedly decreased compared with control or miRNA‑195 negative control treatment group. Together, these data suggest the therapeutic potential of miRNA‑195 in modulating cell growth, migration and apoptosis during the pathophysiological progression of LSCC and that miRNA‑195 may serve as a potential therapeutic target in human LSCC.

Transcriptome-wide Investigation of mRNA/circRNA in miR-184 and Its r.57c > u Mutant Type Treatment of Human Lens Epithelial Cells.

m-miR-184 (mutant miR-184, r.57c > u) appears in familial hereditary ocular diseases, including keratoconus, cataracts, EDICT (endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning) syndrome, severe keratoconus, and non-ectatic corneal thinning. The biological function of m-miR-184 in these ocular diseases remains unclear. With the emergence of high-throughput sequencing, it is now possible to discover many different biological components simultaneously. Using two different RNA libraries, we sequenced the complete transcriptome of HLE cells treated with miR-184, m-miR-184, and a negative control. Data were integrated in an effort to identify any novel gene affected by m-miR-184. Notably, we concluded that ALDH5A1 and GABRA3 were disordered by m-miR-184, which might lead to ocular disease. Moreover, circRNA (circular RNA) expression was highy random across miR-184, m-miR-184, and negative control treatment groups. The sequences of the circRNAs did reveal a particularly high level of ALU sequences. In summary, we provide a new avenue for understanding the role of m-miR-184 in ocular diseases.

Circulating microRNAs as biomarkers of retinal toxicity

Despite of the attrition due to retinal toxicity during drug development there are no early reliable predictive biomarkers of retinal toxicity and this is increasingly becoming a concern. Thus far, in pharmacology and toxicology the technologies for assessing retinal side effects are limited to inconvenient visual behavioral tests, invasive electroretinograms or terminal histopathology. To address the lack of convenient early predictive retinal toxicity biomarkers, we explored a set of potential novel retinal enriched miRNAs in rats ex vivo and in vivo with known retinal toxicant pan-CDK inhibitors to assess circulating plasma miRNAs in rats and non-retinal toxicants as controls. Rats were administered a single intravitreal (IVT) injection and blood samples were collected pre-dose, various time points post-dose and then analyzed for five retinal enriched miRNAs (miR-96, miR-124a, miR181a, miR-182 and miR-183) by qRT-PCR. Ophthalmic exam, electroretinogram and histopathology were performed as confirmatory tests. All five miRNAs tested in retinal explants culture were highly expressed after pan-CDK inhibitor treatment. In vivo the pan-CDK inhibitors caused elevations of miR-96, miR-124a and miR-183 in blood. These results highly correlated with ocular exam, electroretinograms and microscopic findings. Comparatively, there were no changes in miRNA levels, electroretinograms, or histopathology in the negative control treatment groups. Although these miRNAs need additional confirmatory evaluation whether they truly predict retinal toxicity prior to clinical observations and histopathology, these results provide promise for further testing using additional retinal toxicants.

Bioefficacy of Lysine from L-lysine Sulfate and L-lysine??HCl for 10 to 20 kg Pigs

The objective of this study was to compare the bioefficacy of L-lysine sulfate relative to L-lysine·HCl for 10 to 20 kg pigs. Two experiments were conducted to determine the bioefficacy of the two sources of lysine using daily gain, feed conversion, plasma urea nitrogen and nitrogen retention as the response criteria. In experiment 1, 168 crossbred barrows (Landrace×Large White), weaned at 28±3 d (9.07±0.78 kg body weight), were allotted to one of seven dietary treatments in a 2x3 (two lysine sourcesxthree lysine levels) factorial arrangement of treatments with an added negative control treatment group. The basal diet was based on corn, peanut meal and soybean meal and provided 0.67% lysine. The basal diet was supplemented with 0.1, 0.2 or 0.3% lysine equivalents supplied from either L-lysine sulfate or L-lysine·HCl. Each treatment was fed to six pens of pigs with four pigs per pen. The trial lasted 21 days. The relative bioefficacy value of lysine in L-lysine sulfate using daily gain, feed conversion and plasma urea nitrogen as response criteria was 1.01, 1.05 and 1.04 of the lysine in L-lysine·HCl, respectively. In experiment 2, 42 crossbred (Landrace×Large White) pigs (16.03±1.58 kg body weight) were housed in stainless steel metabolism cages for 10 d and fed the seven diets used in the nitrogen-balance trial. The relative bioefficacy value of L-lysine sulfate was estimated to be 0.95 as effective as L-lysine·HCl for nitrogen retention on an equimolar basis. The t-test analysis revealed that bioefficacy of lysine in L-lysine sulfate was not significantly different from lysine in L-lysine·HCl, which was set at 1.00. In conclusion, L-lysine sulfate can be used instead of L-lysine -HCl to fortify lysine-deficient diets fed to 10 to 20 kg pigs.

The Genotoxicity of Priority Polycyclic Aromatic Hydrocarbons (PAHs) Containing Sludge Samples

ABSTRACTIn this research work we developed in vitro tests utilizing mammalian cell cultures, which can rapidly assess effect of exposure of oily sludge-derived chemicals on human and ecological health. Many of these are hazardous to health and environment due to their toxicity and/or accumulation potential in sediments as well as in organisms. Petroleum refinery and petrochemical industry-derived oily sludges contain toxic polycyclic aromatic hydrocarbons (PAHs), some of which are lipophilic in nature. Risk assessment of environmental samples suffers from inadequate availability of toxicity data, lack of knowledge about behavior of genotoxic substances in complex matrices, paucity of information on synergistic and antagonistic interactions of mixture of components, etc.; the literature describing the behavior of genotoxic substances in complex mixtures is sparse and sometimes contradictory. The present study aims at assessing the genotoxic potential of oily sludges collected from an integrated petroleum refinery and petrochemical industry located in the southwestern part of India and a petrochemical industry located in the western part of India using a battery of genotoxicity assays such as DNA damage/strand break, chromosomal aberration, p53 protein induction, and apoptosis in CHO-K1 cell culture system.Exposure with different dose levels of sludge extracts (25, 50, 100 μL) in CHO-K1 cells could cause statistically significant level of (P < 0.001) DNA damage, chromosomal aberration, p53 protein induction, and apoptosis in comparison to negative control treatment groups, and the genotoxicity was attributed to PAHs present in the sludge as identified by GC-MS. This implies that the sludges are genotoxic in nature in mammalian cells tested, and the exposure to these may pose a potential genotoxic risk to human beings.