D3 Group Research Articles

Blood Cadmium Affects the Association between Serum 25-Hydroxyvitamin D3 and Diabetic Retinopathy Severity in the U.S. Population with Type 2 Diabetes.

Serum 25-hydroxyvitamin D3 [25(OH)D3] concentrations have been associated with diabetic retinopathy (DR) severity. Blood cadmium has also been reported to be associated with the presence of DR. Besides, cadmium can decrease the formation of calcitriol (active vitamin D) in blood. However, the effect of blood cadmium on the association between 25(OH)D3 and DR severity has not been studied comprehensively. Therefore, we designed this cross-sectional study to assess the effect modification of blood cadmium on the association between 25(OH)D3 and DR severity in the U.S. population with type 2 diabetes (T2D). This study was conducted using NHANES from 2005 to 2008. By having stratified participants based on blood cadmium category (low blood cadmium<2.76 nmol/L; high blood cadmium≥2.76 nmol/L), we evaluated the difference (interaction test) between the relationship of 25(OH)D3 with the severity of DR among low blood cadmium and high blood cadmium participants using multivariable logistic regression. In this cross-sectional study, a total of 283 participants were included. In the high blood cadmium group, the odds ratio for severe non-proliferative retinopathy (NPDR)/proliferative retinopathy (PDR) of high 25(OH)D3 (≥50 nmol/L) group was 0.26 (95% CIs: 0.09-0.69, p=0.01) compared with the reference group (low 25(OH)D3 group). Furthermore, there was evidence of interaction between 25(OH)D3 and blood cadmium on decreasing the incidence of severe NPDR/PDR. Our study indicated that blood cadmium might affect the association of 25(OH)D3 with DR severity in participants with T2D. More randomized controlled trials are needed to provide more evidence of such a finding.

The Effect Of Indigofera Tinctoria Extract On Cdk5 Expression And Signs Of Inflammation In A Chronic Pain Rat Model

Chronic pain is a challenging case that requires efforts to find effective drugs with minimal side effects. In last decade, Cdk5 become a potential target of chronic pain traetment. Indigofera tinctoria is a plant that grows a lot in Indonesia and has been used for various purposes. This plant is proven to contain indirubin which was proven as a Cdk5 (Cycline dependent kinases 5) inhibitor. The Objective of this research is analyze the effect of Indigofera tinctoria in a chronic pain model. This research was involving 35 rats divided into 5 groups. CFA (Complete Freud’s Adjuvant) solution was injected into the right plantar area to make a chronic pain model. Indigofera tinctoria extract was given orally in 200 mg/KgBW (D1 group), 300 mg/KgBW (D2 group), and 400 mg/KgBW (D3 group). Treatment was given for 7 days after the sign of chronic inflammation were detected (28 days after CFA induction). The analgesic effect was determined by pain latency on the hotplate, the anti-inflammatory effect was evaluated by measuring the hind paw volume. The Cdk5 expression was detected at the dorsal root ganglia by immunohistochemistry method. Results: The mean pain latency value of the D2 and D3 groups was greater than that of the other groups. The inflammatory sign in the treatment group was smaller and significantly different than in the positive control group. Cdk5 expression is not statistically different, however, the treatment group showed a lower Cdk5 expression. Conclusions: Indigofera extract has potential analgesic, anti-inflammatory, and Cdk5 inhibitory effects.

The Effect of Indigofera tinctoria Extract on Cdk5 Expression and Signs of Inflammation in A Chronic Pain Rat Model

Chronic pain is a challenging case that requires efforts to find effective drugs with minimal side effects. In the last decade, Cdk5 has become a potential target of chronic pain treatment. Indigofera tinctoria is a plant that grows abundantly in Indonesia and has been used for various purposes. This plant is proven to contain indirubin which was proven as a Cdk5 (Cyclin dependent kinases 5) inhibitor. The objective of this research is to analyze the effect of Indigofera tinctoria in a chronic pain model. This research was conducted on 35 rats divided into 5 groups. CFA (Complete Freud’s Adjuvant) solution was injected into the right plantar area to make a chronic pain model. Indigofera tinctoria extract was given orally in 200 mg/KgBW (D1 group), 300 mg/KgBW (D2 group), and 400 mg/KgBW (D3 group) doses. Treatment was given for 7 days after the sign of chronic inflammation were detected (28 days after CFA induction). The analgesic effect was determined by pain latency on the hotplate, while the anti-inflammatory effect was evaluated by measuring the hind paw volume. The Cdk5 expression was detected at the dorsal root ganglia by immunohistochemistry method. The mean pain latency value of the D2 and D3 groups was greater than that of the other groups. The inflammatory sign in the treatment group was smaller and differs significantly from the positive control group. Cdk5 expression was not statistically different, however, the treatment group showed a lower Cdk5 expression. Indigofera extract has potential analgesic, anti-inflammatory, and Cdk5 inhibitory effects.

Effects of Dietary Fish Meal Replacement with Composite Mixture of Chicken Meal, Krill Meal, and Plant Proteins on Growth, Physiological Metabolism, and Intestinal Microbiota of Chinese Perch (Siniperca chuatsi)

This trial aimed to investigate the influence of graded replacing fish meal (D1: 0.00%, D2: 27.27%, and D3: 54.55%) with mixed protein ingredients (i.e., chicken meal, krill meal, fermented soybean meal, and soy protein concentrate) on the growth performance, muscle nutritional composition, blood biochemical indices, gut bacterial community, and transcriptome of Chinese perch. Two hundred seventy Chinese perch were divided into three groups (90 per group) and the diet lasted for 56 days. Results showed that the weight gain rate and specific growth rate were significantly lower, and the feed conversion ratio was significantly higher in the D3 group than in fish fed D1 (P&lt;0.05), with no significant differences between the D1 and D2 groups (P&gt;0.05). The muscle crude protein content was highest in the D2 group, and the crude fat content was significantly different in the order: D3 &gt; D1 &gt; D2 (P&lt;0.05). The levels of serum triglycerides (TG) and low-density lipoprotein cholesterol in the D2 group were significantly lower than those in the D1 group (P&lt;0.05), but there was no significant difference compared to the D3 group (P&gt;0.05). The microbial community structure changed significantly. Mycoplasma showed the highest abundance in the D1 and D2 groups (P&lt;0.05), and Cetobacterium peaked in D2 group, and significantly higher than that in D1 group (P&lt;0.05). Network analysis and cohesion index calculation showed that both network complexity and cohesion peaked in D2 group, and Cetobacterium was highly correlated with the cohesion index (P&lt;0.05). Further, muscle transcriptome analysis results showed that compared with the control group, differentially expressed genes were clustered (Q &lt; 0.05) in the arginine and proline metabolism pathways in D2 group. Fish in D3 group significantly (Q &lt; 0.05) affected genes involved in KEGG pathways of ribosome, circadian rhythm, thermogenesis, insulin signaling pathway, fatty acid degradation, oxidative phosphorylation, and apoptosis. In conclusion, under the experimental conditions, the replacement of 27.27% of fish meal by the compound protein did not have a negative impact on the growth performance of Chinese perch and could improve muscle quality, lipid metabolism, and the interaction of intestinal microbiota.

The short- and long-term outcomes of laparoscopic D2 lymphadenectomy plus complete mesogastrium excision for lymph node-negative gastric cancer.

Patients with T1-3N0M0 gastric cancer (GC) who undergo radical gastrectomy maintain a high recurrence rate. The free cancer cells in the mesogastric adipose connective tissue (Metastasis V) maybe the reason for recurrence in these individuals. We aimed to evaluate whether D2 lymphadenectomy plus complete mesogastrium excision (D2 + CME) was superior to D2 lymphadenectomy with regard to safety and oncological efficacy for T1-3N0M0 GC. Patients with T1-3N0M0 GC who underwent radical resection from January 2014 to July 2018 were retrospectively analyzed; there were 323 patients, of whom 185 were in the D2 + CME group and 138 in the D2 group. The primary endpoint was 5-year disease-free survival (DFS). Secondary endpoints include the 5-year overall survival (OS), recurrence pattern, morbidity, mortality, and surgical outcomes. D2 + CME was associated with less intraoperative bleeding loss, a greater number of lymph nodes harvested, and less time to first postoperative flatus, but the postoperative morbidity was similar. The 5-year DFS was 95.6% (95% CI 92.7-98.5%) and 90.4% (95% CI 85.5-95.3%) in the D2 + CME group and the D2 group, respectively, with a hazard ratio (HR) of 0.455 (95% CI 0.188-1.097; p = 0.071). In terms of recurrence patterns, local recurrence was more prone to occur in the D2 group (p = 0.031). Subgroup analysis indicated that for patients with T1b-3N0M0 GC, the 5-year DFS in the D2 + CME group was considerably greater than that in the D2 group (95.3% [95% CI 91.6-99.0%] vs. 87.6% [95% CI 80.7-94.5%], HR 0.369, 95% CI 0.138-0.983; log-rank p = 0.043). Laparoscopic D2 + CME for T1-3N0M0 GC is safe and feasible. Furthermore, it not only reduces the local recurrence rate but also improves the 5-year DFS in cases of T1b-3N0M0 GC.

The Effects of High Calcium and Vitamin D on the Fructose- Induced Lipogenesis Pathway in Rats

In this study the protective effects of high amounts of dietary calcium and vitamin D on fructose-induced lipogenesis were investigated at molecular and biochemical levels. Control group (Con, n=8), High fructose diet group (F, n=8), High fructose diet+75 mg CaCO3 and 26.4 IU vitamin D3 group (FCaD1, n=8), High fructose diet+150 mg CaCO3 and 52.8 IU vitamin D3 group (FCaD2, n=8) including experimental groups were fed for 28 days. The significant difference between the living weights was determined firstly as 278.64±5.61a; 268.94±2.80ab; 257.93±4.86b and 257.38±3.42b g in the Con, F, FCaD1, FCaD2 groups, respectively, at the end of the first week (P

The effect of B groups vitamins (B1, B2, B5, B6, B10, B12) on the activity of antioxidants protection system enzymes and the content of lipids peroxide oxidation products in the blood of feeding cattle

The article highlights the specifics of the effect of various doses of a complex of B vitamins (B1, B2, B5, B6, B10, B12) on the activity of critical enzymes of the body's antioxidant defense system (superoxide dismutase, catalase, glutathione peroxidase) and the content of peroxide oxidation products (diene conjugates and Malan dialdehyde) in the blood of cattle at the final stage of fattening. The research was conducted during the winter-spring stall on 12-month-old Ukrainian black-spotted dairy cows. According to the principle of analogs, five groups of experimental animals (control and four experimental) were formed, each with six heads. The experiment lasted six months. The rations for the research groups of Bugai cattle are prepared by the recommended norms, taking into account the chemical composition of the fodder of the given area, the age of the animals, live weight, and the planned average daily growth. The silage type of fattening was used for feeding the Bugai cattle. The basis of our dosage of various vitamins of group B for fattening steers of experimental groups is the appropriate percentage of the recommended doses of individual vitamins of group B for fattening pigs (10 % – D1, 20 % – D2, 40 % – D3, 60 % – D4 group). The conducted studies established that the addition of a complex of B vitamins (B1, B2, B5, B6, B10, B12) balanced in terms of nutrients and minerals and fat-soluble vitamins A, D, E to the diet of fattening bulls in appropriate doses causes an increase in activity of critical enzymes of the antioxidant defense system in the blood of fattening bulls (the activity of superoxide dismutase increases the most (by 8.9–28.4 %)) and a decrease in the content of both primary (diene conjugates) and secondary (malanic dialdehyde) products of lipid peroxidation in the blood of fattening bulls, which depends on the dose of B vitamins added to the diet (B1, B2, B5, B6, B10, B12). The most significant change in terms of morphological composition in animals third (B1 – 0.040; B2 – 0.06; B5 – 1.2; B6 – 0.25; B10 – 0.0030; B12 – 0.0006 mg/kg body weight) and fourth (B1 – 0.070; B2 – 0.10; B5 – 2.0; B6 – 0.40; B10 – 0.0050; B12 – 0.0010 mg/kg body weight) research groups, and smallest – in bull Ist (B1 – 0.015; B2 – 0.03; B5 – 0.5; B6 – 0.10; B10 – 0.0012; B12 – 0.0002 mg/kg body weight) and research group, which is associated with dose introduced to the diet of calves during the final fattening phase of B vitamins (B1, B2, B5, B6, B10, B12).

Complete mesocolic excision for right colon cancer: Is D3 lymphadenectomy necessary?

Although complete mesocolic excision (CME) for colon cancer is oncologically sound, to date, there has been no consensus on the extent of lymphadenectomy in radical right colectomy. This study essentially compared the perioperative and survival outcomes of CME with two templates of lymphadenectomy for right colon cancer. This was a propensity matched, retrospective analysis of a single centre, prospectively maintained database of all patients undergoing elective right colectomy for nonmetastatic, biopsy-proven adenocarcinoma from November 2013 to October 2018. CME + D3 was adopted selectively, documented prospectively, and compared with patients undergoing CME + central vascular ligation (CVL). The only technical difference between the groups was the excision of the surgical trunk of Gillot in the CME + D3 group. Postoperative, long-term outcomes and patterns of recurrence were compared between the groups. Of the 244 eligible patients, 88 (36.1%) and 156 (63.9%) underwent CME + D3 and CME + CVL, respectively. Matched groups (72 [CME + D3] vs. 108 [CME + CVL]) showed no difference in histology, tumour grade, postoperative complications, mortality, and hospital stay. CME + D3 was preferentially performed laparoscopically (35.2% vs. 9%), was associated with lower blood loss (215 mL vs. 297 mL, p = 0.001), higher nodal yield (31 vs. 25 nodes, p = 0.003) and a higher incidence of chyle leak (4 vs. 0, p = 0.013). At a median follow-up of more than 57 months, there was no significant difference in local recurrence, disease-free or overall survival. In this retrospective study, lymphadenectomy along the superior mesenteric vein, as a component of CME for right colon cancer, offered a higher nodal yield with no improvement in oncological outcome. Dissection of the SMV, over and above a D2 dissection, could therefore be restricted to specialized colorectal units until further studies establish the incremental oncological benefit of this extended lymphadenectomy or define a patient group in whom it is beneficial.

Effects of dietary supplementation with organic acids mixture on growth, feed efficiency, hematobiochemical parameters, immunity, and intestinal microbiota of Gilthead seabream (Sparus aurata) juveniles

This trial assessed for 90 days the influences of dietary organic acids mixture (Aquagest ® OM) on the performance of Gilthead sea bream (Sparus aurata; n = 360; initial weight= 9.15 ± 0.10 g). A diet without organic acids supplement was specified as control (D0), whereas another five diets were supplemented by 0.1%, 0.2%, 0.3%, 0.4%, and 0.5% for diets D1, D2, D3, D4, and D5, respectively. The fish fed on the control diet [D0] and 0.5% organic acids mixture-based diet [D5] exhibited the lowest final weight [Wt.90], weight gain [Wt.G.], average daily gain [A.D.G.], specific growth rate [S.G.R.], and feed intake [F.I.], as well as the highest feed conversion ratio [F.C.R.]. In comparison, the best results were with 0.2% and 0.3% organic acids mixture-based diets [D2 and D3]. The condition factor (K) rises when the amount of organic acid mixture in the diet is increased ≥ 0.2% [D2 – D5]. At the same time, the highest hepatosomatic indices [H.S.I.] were in the D5 and D1 groups. Furthermore, the lowest values for hemoglobin, hematocrit, and red blood cells [RBCs] were observed in fish fed a basal diet, and the highest records were in fish-fed D2 and D3 diets. The best lysozyme and phagocytic activities were in D2 and D3 groups. Regarding total bacterial count, Vibrio, and Escherichia coli, fish given a basal diet (D0) showed the highest microbiota records, while fish fed on diets fortified with organic acids exhibited lower counts. No alterations between the experimental groups in body proximate composition, white blood cells [WBCs], total proteins, alanine transaminase [ALT], aspartate transaminase [AST], albumin, urea, creatinine, and acid-fermentative bacteria counts. In conclusion, based on the polynomial regression analysis of S.G.R., F.C.R., lysozyme activity, and phagocytic activity on organic acids levels, the optimal levels of the organic acids mixture ranged from 0.18% to 0.28%.

Pediatric intensive care unit treatment alters the diversity and composition of the gut microbiota and antimicrobial resistance gene expression in critically ill children.

Common critical illnesses are a growing economic burden on healthcare worldwide. However, therapies targeting the gut microbiota for critical illnesses have not been developed on a large scale. This study aimed to investigate the changes in the characteristics of the gut microbiota in critically ill children after short-term pediatric intensive care unit (PICU) treatments. Anal swab samples were prospectively collected from March 2021 to March 2022 from children admitted to the PICU of Xinhua Hospital who received broad-spectrum antibiotics on days 1 (the D1 group) and 7 (the D7 group) of the PICU treatment. The structural and functional characteristics of the gut microbiota of critically ill children were explored using metagenomic next-generation sequencing (mNGS) technology, and a comparative analysis of samples from D1 and D7 was conducted. After 7 days of PICU admission, a significant decrease was noted in the richness of the gut microbiota in critically ill children, while the bacterial diversity and the community structure between groups remained stable to some extent. The relative abundance of Bacilli and Lactobacillales was significantly higher, and that of Campylobacter hominis was significantly lower in the D7 group than in the D1 group. The random forest model revealed that Prevotella coporis and Enterobacter cloacae were bacterial biomarkers between groups. LEfSe revealed that two Gene Ontology entries, GO:0071555 (cell wall organization) and GO:005508 (transmembrane transport), changed significantly after the short-term treatment in the PICU. In addition, 30 KEGG pathways were mainly related to the activity of enzymes and proteins during the processes of metabolism, DNA catabolism and repair, and substance transport. Finally, 31 antimicrobial resistance genes had significantly different levels between the D7 and D1 groups. The top 10 up-regulated genes were Erm(A), ErmX, LptD, eptB, SAT-4, tetO, adeJ, adeF, APH(3')-IIIa, and tetM. The composition, gene function, and resistance genes of gut microbiota of critically ill children can change significantly after short PICU treatments. Our findings provide a substantial basis for a better understanding of the structure and function of gut microbiota and their role in critical illnesses.

Effect of recombinant bovine somatotropin on the reproductive efficiency of beef cows subjected to differently timed-artificial insemination protocols.

This study aimed to verify the reproductive efficiency of beef cows treated with recombinant bovine somatotropin (rbST). Study 1, Bos indicus cows were distributed (three groups). The control group (CG) was subjected: on day zero (d0), the animals received a CIDR and oestradiol benzoate (EB); on (d8, CIDR was removed, and PGF2α and oestradiol cypionate (EC) were administered; on d10, timed Artificial Insemination (TAI) was performed; on d45, pregnancy diagnosis was made. The rbST on d0 group (bST0G) was subjected to an identical protocol as CG, except for the addition of 250 mg rbST on d0. The rbST on d8 group (bST8G) was subjected to the same protocol as bST0G, except that the rbST was administered on d8 rather. In study 2, the animals followed the same design which was used in Bos taurus cows. The follicular growth rate (FGR) was calculated between d8 and d10. In study 1, pregnancy/artificial insemination (P/AI) did not differ among the treatments. FGR in bST8G was higher than in other groups. In study 2, bST0G showed higher Pregnancy/Artificial Insemination (P/AI) (p < .05) when compared with other groups. bST0G showed a different FGR (p < .0001) than the other groups. In conclusion, rbST (Bos indicus cows) did not increase P/AI, but it did promote follicular growth when administered on d8; the rbST administered on d0 improved P/AI (p < .05) and the FGR in Bos taurus cows.

Hippocampal mitochondrial Ca++ in experimentally induced Alzheimer's disease, link to calpains and impact of vitamin D3 supplementation

ObjectiveVitamin D impact on hippocampal mitochondrial Ca++ and calpains was not previously investigated in Alzheimer's disease (AD). The current work aimed to assess the alteration in hippocampal mitochondrial Ca++, ATP & ADP and hippocampal calpains' level in (AlCl3)-induced AD model, and the effect of 2 regimens of vitamin D supplementation on these alterations. Methods: Forty male Wistar rats were randomized into 4 groups; control, AD (AlCl3100 mg/kg, p.o. daily for 42 days), AD and vitamin D co-treated group (AlCl3 as in AD group with vitamin D3 400 IU/kg/day, p.o. for 42 days) and AD, followed by vitamin D3 group (AlCl3 was given as in AD group for 42 days, then vitamin D3 for two weeks). AD was assessed by hippocampal levels of Aβ42, p-tau and spatial memory assessment in Morris water maze. Hippocampal mitochondrial Ca++, ATP and ADP levels besides to calpain-1 & 2 and cytochrome C were assessed in addition to CA1 histological examination. Results: AD animals showed impaired mitochondrial function as denoted by high Ca++ and decreased ATP and ADP and elevated calpain-1 & 2 and cytochrome C. Hippocampal CA1 region showed increased degenerated neurons and reduced thickness of its pyramidal layer. Vitamin D administration minimized the hippocampal mitochondrial impairement induced by AD and mitigated histological alterations even when supplemented post AD establishment. Conclusion: Vitamin D administration to AD rats breaks the deleterious loop in the hippocampus that involves increased Ca++, calpain activation, mitochondrial failure, neuronal degeneration and AD disease progression.

Combined probiotics with vitamin D3 supplementation improved aerobic performance and gut microbiome composition in mixed martial arts athletes.

Mixed Martial Arts (MMA) is characterized as an interval sport in which the training program focuses on enhancing both aerobic and anaerobic capacities. Therefore, strategies targeting the intestinal microbiome may be beneficial for MMA athletes. Moreover, vitamin D supplementation may amplify the positive effects of certain bacterial strains. We previously demonstrated that the combined of probiotics and vitamin D3 supplementation improved the lactate utilization ratio, total work, and average power achieved during anaerobic tests in MMA. Therefore, this study aimed to investigate whether combined probiotic and vitamin D3 ingestion can modify the composition of the gut microbiome and epithelial cell permeability, influence the inflammatory response, and ultimately enhance aerobic capacity. A 4-week clinical trial was conducted with 23 male MMA athletes randomly assigned to either the probiotic + vitamin D3 (PRO + VIT D) group or the vitamin D3 group (VIT D). The trial employed a double-blind, placebo-controlled design and involved measurements of serum inflammatory markers, gut microbiome composition, epithelial cell permeability, and aerobic performance. After 4-week of supplementation, we found a significantly lower concentration of calprotectin in the PRO + VIT D group (34.79 ± 24.38 mmol/L) compared to the value before (69.50 ± 46.91) supplementation (p = 0.030), augmentation of beta diversity after the intervention in the PRO + VIT D group (p = 0.0005) and an extended time to exhaustion to 559.00 ± 68.99; compared to the value before (496.30 ± 89.98; p = 0.023) after combined probiotic and vitamin D3 supplementation in MMA athletes. No effect was observed in the VIT D group. Our results indicate that combined treatment of probiotics and vitamin D3 may cause alterations in alpha and beta diversity and the composition of the gut microbiota in MMA athletes. We observed an improvement in epithelial cell permeability and an extended time to exhaustion during exercise in MMA athletes following a 4-week combined probiotic and vitamin D3 treatment.

On the Jahn-Teller Effect in Silver Complexes of Dimethyl Amino Phenyl Substituted Phthalocyanine.

The structures of Ag complexes with dimethyl amino phenyl substituted phthalocyanine m[dmaphPcAg]q of various charges q and in the two lowest spin states m were optimized using the B3LYP method within the D4h symmetry group and its subgroups. The most stable reaction intermediate in the supposed photoinitiation reaction is 3[dmaphPcAg]-. Group-theoretical analysis of the optimized structures and of their electron states reveals two symmetry-descent mechanisms. The stable structures of maximal symmetry of complexes 1[dmaphPcAg]+, 3[dmaphPcAg]+, 2[dmaphPcAg]0, and 4[dmaphPcAg]2- correspond to the D4 group as a consequence of the pseudo-Jahn-Teller effect within unstable D4h structure. Complexes 4[dmaphPcAg]0, 1[dmaphPcAg]-, 3[dmaphPcAg]-, and 2[dmaphPcAg]2- with double degenerate electron ground states in D4h symmetry structures undergo a symmetry descent to stable structures corresponding to maximal D2 symmetry, not because of a simple Jahn-Teller effect but due to a hidden pseudo-Jahn-Teller effect (strong vibronic interaction between excited electron states). The reduction of the neutral photoinitiator causes symmetry descent to its anionic intermediate because of vibronic interactions that must significantly affect the polymerization reactions.

Clinical significance of extrahepatic bile duct resection for T2 gallbladder cancer using data from the Japanese Biliary Tract Cancer Registry between 2014 and 2018.

The present study aimed to determine whether concomitant extrahepatic bile duct resection (EHBDR) improves the prognosis of patients with T2 gallbladder cancer (GBC). Between 2014 and 2018, 4947 patients with GBC were registered in the National Biliary Tract Cancer Registry in Japan. This included 3804 patients (76.9%) who underwent curative-intent surgical resection; 1609 of these patients had pT2 GBC with no distant metastasis. Of the 1609 patients with GBC, 520 underwent EHBDR and 1089 did not. We compared the patients' backgrounds and disease-specific survival rates between the groups. The frequency of lymph node metastasis was significantly higher in the EHBDR group than in the non-EHBDR group (38.2% vs. 20.7%, p < .001). In the entire cohort, however, there was no significant difference in disease-specific survival between the two groups (76% vs. 79%, p = .410). The EHBDR group had a significantly higher incidence of postoperative complications (Clavien-Dindo classification grade = 3) (32.4% vs. 11.7%, p < .001). When we focused on the survival of only T2N1 patients who underwent gallbladder bed resection, the prognosis was significantly improved for the EHBDR group (5-year survival rate: 64% vs. 54%, p = .017). The non-EHBDR group was subcategorized into two groups: D2 dissection and D1 dissection or sampling, and survival curves were compared between these subgroups. Although the EHBDR group tended to have a favorable prognosis compared to the D2 group, this difference was not significant (p = .167). However, the EHBDR group had a significantly greater prognosis than the D1 dissection or sampling group (5 year-survival rate: 64 vs. 49%, p = .027). The EHBDR may improve the prognosis of patients with T2 gall bladder cancer with lymph node metastases; however, its indication should be carefully determined because of the increased risk of postoperative complications.

Vitamin D3 supplementation improves spatial memory, muscle function, pain score, and modulates different functional physiological biomarkers in vitamin D3 deficiency diet (VDD)-induced rats model

BackgroundVitamin D Deficiency is recognized as a pandemic, which is associated with high mortality. An inadequate level of vitamin D is associated with autoimmune diseases, hypertension, and cancer. The study was aimed to assess the pharmacological effects of chronic vitamin D3 supplementation on the manipulation diet regiment of deprived cholecalciferol (vitamin D3 deficient diet, VDD) rats.MethodsMemory performance (Y-maze task), muscular function (muscle grip strength), and pain score (pressure application measurement meter) were measured. Functional biomarkers were measured using ELISA method in different matrix viz. in serum (parathyroid hormone; PTH, calcitonin, thyroxine, and C-reactive protein; CRP, 25-OH Vit D3), and in CSF (klotho and β-endorphin). 25-OH Vit D3 was also estimated in liver and kidney homogenate using ELISA. Vitamin D receptor (VDR) was measured spectrophotometrically in liver and adipose tissue.ResultsVDD-induced rats showed a decrease in number of entries and time spent in the novel arm and spontaneous alternations in the Y-maze task. Significant improvements of neuromuscular function and pain score after addition of vitamin D3. In comparison to the VDD group, VDR expression (liver) and active metabolites of vitamin D3 (25-OH vit.D3) in serum were significantly higher by 48.23% and 280%, respectively. The PTH and CRP levels were significantly reduced by 32.5% and 35.27%, respectively, whereas calcitonin was increased by 36.67% compared with the VDD group. Klotho and β-endorphin expressions in cerebrospinal fluid were significantly elevated by 19.67% and 133.59%, respectively, compared to VDD group.ConclusionsOverall, the results indicate that supplementation of cholecalciferol significantly improved spatial memory impairment, VDR expression, and may provide an opportunity to manage vitamin D deficiencies.

Ultrastructural Changes and Inflammatory Processes of Day-Dependent Cisplatin Administration on Rat Cardiac Tissue

Aim: Cisplatin (CP) is used to treat a variety of cancers as a chemotherapeutic agent. This drug has also severe side effects and its use exhibits serious toxicity in a number of organs, including kidney and heart. The aim of the present study was to evaluate the ultrastructural and inflammatory changes induced by CP treatment in rat cardiac tissue in a time-dependent manner.&#x0D; Material and Methods: Rats were randomly divided into three experimental groups; control (only saline), CP D2 (treated with CP 2.5 mg/kg/day for 2 days), and CP D7 (treated with CP 2.5 mg/kg/day for 7 days). Cardiac tissues were examined under an electron microscope. Inflammation markers including tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) were analyzed by immunohistochemistry. In addition, electrocardiography was performed to measure the electrical activity.&#x0D; Results: The ultrastructural analysis of the CP D7 group revealed that myofibrils were disrupted and disorganized, mitochondria degenerated, and interstitial edema developed. When compared to the control and CP D2 groups, there was a noticeable increase in the level of TNF-α and IL-1β expression in the CP D7 group according to immunohistochemistry results. Electrocardiography showed that RR interval was longer in CP D7 than CP D2 and control groups.&#x0D; Conclusion: CP for 7 days damaged the ultrastructural morphology in cardiac tissue. Therefore, these findings suggest that the potential therapeutic approaches to reduce mitochondrial damage and inflammation against toxicity caused by CP may provide for clinically significant prevention when using the drug for an extended period of time.

Analysis of the Pathogenesis of Gram-Negative Bacterial Sepsis in Rats Under Nano-Body

This work aimed to evaluate the effectiveness of several anti-TLR4 nanobody administration techniques in a gram-negative bacterial sepsis (GNBS) rat model. The targeting proteins for TI-Nb2 and TC-Nb6 anti-TLR4 nanobodies were TLR4203-348 and TLR4349-582, respectively. The survival times (STs) of 44 Sprague-Dawley (SD) rats were tracked in the TI-Nb2, TC-Nb6, TI-Nb2+TC-Nb6, and D0 groups (saline control). Besides, the ELISA was utilized to measure the levels of TNF-, IL-1, IL-8, and IL-10 in different groups. An automatic biochemical analyzer was employed to determine the levels of AST, ALT, AMS, CRE, and Urea. Furthermore, the rat liver and kidney tissue samples were stained with hematoxylin-eosin (HE). Cleaved-caspase-3 (CC3) protein expression (PE) in rat tissues was discovered using immunohistochemistry, and the positive unit (PU) value was computed. The TI-Nb2+TC-Nb6 group exhibited a longder ST, lower TNF-α, IL-1β, IL-8, ALT, AST, AMS, CRE, and Urea levels, and a smaller CC3 protein PU value in nucleus and cytoplasm than the TI-Nb2, TC-Nb6, and D0 groups (all P &lt;0.05). The above findings indicated that the combined usage of TI-Nb2 and TC-Nb6 can successfully reduce the expression levels of CC3 protein, biochemical markers, and inflammatory factors. This could protect the liver, kidneys, and other organs and prolong the ST of sepsis rats.

824 Complete Mesocolic Excision Is Safe and Results in Increased Lymph Node Harvest: Further Justification for Randomised Trials

Abstract Aim Complete mesocolic excision (CME) for right hemicolectomy encompasses embryonic dissection planes, radical lymphadenectomy and vascular pedicle ligation at the origin. Compared to conventional D2 dissection, CME is associated with increased disease-free survival in population studies. Critics argue that morbidity from CME may be higher. We sought to examine complication rates and specimen oncologic characteristics in a cohort from a single NHS trust. Method We conducted a retrospective cohort study of all right hemicolectomies performed for adenocarcinoma between 3/1/2019 and 15/11/2022. The choice of CME or D2 lymphadenectomy was at the discretion of the operating surgeon. Data were collected from paper notes and electronic records. Statistical analyses used non-parametric testing. Results CME was performed in 30 patients and D2 resection in 99. The CME group were younger (70 vs. 72 years, p = 0.04) and preoperative nodal staging was higher. There were no differences in duration of surgery, estimated blood loss, postoperative haemoglobin or transfusion requirement. Only 20% patients in the CME group had a significant complication compared to 40% of the D2 group (p = 0.05) and length of stay was reduced (5 vs. 7 days, p = 0.02). Nodal harvest was increased in the CME group (24 vs. 19, p = 0.01) with no difference in R0 resection rate. Conclusions CME appears to be safe and does not result in increased complication rates in this single institution cohort. Nodal harvest is increased with comparable margin clearance. Whether this translates to increased disease-free survival is unclear. There is equipoise and randomised studies examining long-term outcomes are justified.

A comparative absorption study of sucrosomial® orodispersible vitamin D3 supplementation vs. a reference chewable tablet and soft gel capsule vitamin D3 in improving circulatory 25(OH)D levels in healthy adults with vitamin D deficiency-Results from a prospective randomized clinical trial.

Vitamin D (Vit D) deficiency (VDD), associated with diverse health conditions, is commonly treated with Vit D3 supplements. However, the gastrointestinal (GI) absorption of Vit D3 in different formulations has not been well studied. We aimed to compare the absorption of an innovative phospholipids-sucrester matrix biodelivery vehicle-based (sucrosomial®) orodispersible Vit D3 preparation against a reference chewable tablet and soft gel capsule (SGC) Vit D3 formulations in Vit D-deficient healthy adults. In study 1, 25 subjects were randomized to receive a weekly single dose of 200,000 IU of sucrosomial® Vit D3 (n = 12) or chewable tablet Vit D3 (n = 13) for 3 weeks. In study 2, 20 subjects were randomized to receive a single dose of 200,000 IU every other week of sucrosomial® Vit D3 (n = 10) or SGC Vit D3 (n = 10) for 6 weeks. Circulatory 25-hydroxyvitamin D3 [25(OH)D] levels were reassessed after 2, 3, and 6 weeks in study 1 and after 4 and 6 weeks in study 2. In study 1, after 2 weeks, circulatory 25(OH)D levels increased significantly in both Vit D3 treatment groups (p < 0.0001) but improved markedly in the sucrosomial® Vit D3 group, with no further considerable change after 3 and 6 weeks in both groups. Overall, at all three follow-ups, sucrosomial® Vit D3 treatment achieved significantly higher and sustained 25(OH)D levels (p < 0.001). In study 2, after 4 weeks, both Vit D3 treatment groups showed significant improvement in circulatory 25(OH)D levels (p < 0.0001) but substantially higher in the sucrosomial® group with statistically significant differences between the two treatment groups (p = 0.02). At the 6-week follow-up, only subjects in the sucrosomial® Vit D3 group showed a further increase in circulatory 25(OH)D levels (p = 0.049), but no further significant changes in the levels of the SGC Vit D3 group (p = 0.062), showing a statistically significant difference between the two treatment groups (p = 0.002). The Vit D3 treatment was well tolerated by all participants, and no treatment-emergent effects or serious adverse events were reported. Our results suggest that the sucrosomial® Vit D3 preparation absorbs efficiently in the GI system, achieving adequately higher and sustained circulatory Vit D levels in VDD, and thus can effectively contribute to the body protection against VDD-associated health conditions. clinicaltrials.gov, identifier: NCT05706259.