Decreased Alkaline Phosphatase Research Articles

Oncostatin M promotes osteogenic differentiation of tendon-derived stem cells through the JAK2/STAT3 signalling pathway

PurposeOncostatin M (OSM) is involved in the regulation of osteogenic differentiation and has a major role in the development of heterotopic ossification. The role of OSM in osteogenic differentiation of tendon-derived stem cells (TDSCs) and its mechanism have not been reported. This study aim to investigate the role of OSM in osteogenic differentiation of TDSCs and study the mechanism.MethodsTDSCs were differentiated in osteogenic differentiation medium for 7 days. Recombinant OSM was added to the osteogenic differentiation medium for 7 and 14 days. The effect of Janus kinase 2 (JAK2) inhibitor AZD1480 and signal transducer and activator of transcription 3 (STAT3) inhibitor stattic in the presence of recombinant OSM on osteogenic differentiation of TDSCs was examined after differentiation for 7 and 14 days. Alkaline phosphatase and alizarin red staining were used to assess the effects on early and mid-stage osteogenic differentiation, respectively. Western blotting and qPCR were used to assess the expression of receptor and signalling pathway-related proteins and osteogenic marker genes, respectively.ResultsTDSCs were successfully induced to differentiate into osteoblasts. Recombinant OSM promoted osteogenic differentiation of TDSCs to early and mid-stages. After addition of AZD1480 or stattic, decreased alkaline phosphatase and alizarin red staining were observed in the early and mid-stages of osteogenic differentiation. Additionally, decreased expression of receptor and pathway-related proteins, and osteogenic genes was found by western blotting and qPCR, respectively.ConclusionOSM promotes osteogenic differentiation of TDSCs and the JAK2/STAT3 signalling pathway plays an important role.

Anti-Menopausal Effect of Heat-Killed Bifidobacterium breve HDB7040 via Estrogen Receptor (ER)-Selective Modulation in MCF-7 Cells and Ovariectomized Rats.

Menopause is induced by spontaneous ovarian failure and leads to life quality deterioration with various irritating symptoms. Hormonal treatment can alleviate these symptoms, but long-term treatment is closely associated with breast and uterine cancer, and stroke. Therefore, developing alternative therapies with novel anti-menopausal substances and improved safety is needed. In our study, heat-killed Bifidobacterium breve HDB7040 significantly promoted MCF-7 cell proliferation in a dose-dependent manner under estrogen-free conditions, similar to 17β-estradiol. This strain also triggered ESR2 expression, but not ESR1, in MCF-7 cells. Moreover, administrating HDB7040 to ovariectomized (OVX) Sprague-Dawley (SD) female rats reduced estrogen deficiency-induced weight gain, fat mass, blood triglyceride, and total cholesterol levels. It also recovered collapsed trabecular microstructure by improving trabecular morphometric parameters (bone mineral density, bone volume per tissue volume, trabecular number, and trabecular separation) and decreasing blood alkaline phosphatase levels with no significant changes in uterine size and blood estradiol. HDB7040 also significantly regulated the expression of Tff1, Pgr, and Esr2, but not Esr1 in uteri of OVX rats. Heat-killed B. breve HDB7040 exerts an anti-menopausal effect via the specific regulation of ERβ in vitro and in vivo, suggesting its potential as a novel substance for improving and treating menopausal syndrome.

Влияние внутрижелудочного введения гидрокарбоната натрия или соляной кислоты на кишечную эндотоксемию у крыс при миелоабляции циклофосфамидом

Toxic effects of the myeloablative cyclophosphamide (CP) doses include damage to the gastrointestinal tract. This is manifested by gastrointestinal stasis, cytostatic drug-induced damage to the small intestinal mucosa, and acute gut-derived endotoxemia. The study was aimed to identify causal relationships between gastrointestinal stasis, enterocytopenia, and acute gut-derived endotoxemia in the rat model of the CP myeloablative conditioning. We assessed the effects of the intragastrically administered 0.48 М sodium bicarbonate (NaHCO3) solution or the 0.1 М hydrochloric acid (HCl) solution on the indicators of gastrointestinal stasis, enterocytopenia, portal blood levels of endotoxin, ammonia, urea, and urinary indican excretion. The stomach overfilled with chyme, decreased alkaline phosphatase and cholinesterase activity in the small intestinal tissues, 4.4-fold increased endotoxin levels, 4.6-fold increased urea levels, twofold increased portal blood plasma creatinine levels, and twofold increased urinary indican excretion were observed three days after intravenous administration of CP in a dose of 390 mg/kg. Intragastric administration of NaHCO3 or HCl partially prevented gastric stasis, but not acute gut-derived endotoxemia. Administration of NaHCO3, not HCl, prevented enterocytopenia in the duodenum. Acute gut-derived endotoxemia resulted mainly from the more intense release of the cecal microflora waste products into blood. Testing the use of sodium bicarbonate intragastric administration combined with the enteral detoxification and/or options for suppression of colonic microflora vegetation for prevention of the myeloablative cytostatic therapy complications is promising.

Luteolin attenuates CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11.

Luteolin (3,4,5,7-tetrahydroxy flavone) is reported to strongly protect from acute carbon tetrachloride (CCl4) -induced liver injury or fibrosis. Ferroptosis can be induced by hepatic injury, and contributes to liver fibrosis development. The exact functional mechanism underlying luteolin inhibition of hepatic injury and whether ferroptosis is involved are unclear. Mice model and cell model of liver injury were constructed or induced to explore the effect and molecular mechanisms of Luteolin in the treatment of hepatic injury using CCl4. Cell Counting Kit-8 (CCK-8) and flow cytometry were used to evaluate HepG2 cell viability and apoptosis. The differential expressed genes involved in liver injury were scanned using RNA-seq and confirmed using functional study. Western blot was used to detect the indicators related to ferroptosis. Luteolin attenuated hepatic injury by alleviating cell morphology and decreasing serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels in vivo mice models, and increasing cell viability, downregulating arachidonate 12-lipoxygenase (ALOX12), cyclooxygenase-2 (COX-2) and P21 protein expression, suppressing apoptosis in vitro cell models. Luteolin also inhibited ferroptosis by stimulating glutathione peroxidase 4 (GPX4) and mitochondrial ferritin (FTMT) protein expression, increasing glutathione (GSH) content, and minimizing Fe2+ and malondialdehyde (MDA) levels. Solute carrier family 7a member 11 (SLC7A11) was identified to be a key regulatory gene that participated in luteolin attenuation of CCl4-induced hepatic injuries in HepG2 cells using Microarray assay. Functional study showed that SLC7A11 can alleviate hepatic injury and ferroptosis. Luteolin attenuated CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11. SLC7A11 may serve as a novel alternative therapeutic target for hepatic injury.

Negative Regulation of LINC01013 by METTL3 and YTHDF2 Enhances the Osteogenic Differentiation of Senescent Pre-Osteoblast Cells Induced by Hydrogen Peroxide.

Senescent pre-osteoblasts have a reduced ability to differentiate, which leads to a reduction in bone formation. It is critical to identify the keys that regulate the differentiation fate of senescent pre-osteoblasts. LINC01013 has an essential role in cell stemness, differentiation, and senescence regulation. This study aims to examine the role and mechanism of LINC01013 in regulating osteogenic differentiation in senescent human embryonic osteoblast cell line (hFOB1.19) cells induced by hydrogen peroxide (H2O2). The results show that LINC01013 decreased alkaline phosphatase activity, mineralization of hFOB1.19 cells in vitro, and the expression of collagen II, osteocalcin, and bone sialoprotein. LINC01013 knockdown enhances the osteogenesis of hFOB1.19 cells and rescues osteogenic differentiation impaired by H2O2. METTL3 negatively regulates LINC01013 expression, enhancing hFOB1.19 cells' osteogenesis in vitro and in vivo. METTL3 overexpression can enhance hFOB1.19 cells' osteogenic differentiation impaired by H2O2. YTHDF2 promotes LINC01013 decay, facilitating osteogenic differentiation. YTHDF2 overexpression rescues hFOB1.19 cells osteogenic differentiation impaired by H2O2. Taken together, METTL3 upregulates osteogenic differentiation by inhibiting LINC01013, and YTHDF2 accelerates LINC01013 degradation, reducing its inhibitory effect. This study highlights LINC01013 as a key regulator in the fate switching process of senescent hFOB1.19 cells, impacting osteogenic differentiation.

Age-related changes in hematological and biochemical profiles of Wistar rats

BackgroundWistar rats are extensively used as the model for assessing toxicity and efficacy in preclinical research. Hematological and biochemical laboratory data are essential for evaluating specific variations in the physiological and functional profile of a laboratory animal. Establishing hematological and biochemical reference values for Wistar (han) rats at various age intervals was the goal of this work. Male and female Wistar rats (n = 660) of ages 6–8 weeks, 10–14 weeks and > 6 months were used in the experiment. Blood and serum were collected from these rats under fasting conditions.ResultsWe observed that the majority of hematological and biochemical parameters were significantly influenced by sex and age. Hematological changes were significantly correlated to aging were increased red blood cells, hemoglobin, hematocrit, neutrophils, monocytes and eosinophils in both sexes, as well as decreased platelet, mean corpuscular volume, mean corpuscular hemoglobin and lymphocytes in both sexes. White blood cells of male rats were considerably higher than those of female rats in all age ranges. For biochemistry, increase in glucose, total protein and creatinine were seen in both sexes, along with increases in urea in females and alanine aminotransferase in males. Age was significantly associated with decreased alkaline phosphatase in both sexes.ConclusionsWhen using Wistar rats as a model, these reference values may be useful in evaluating the results.

Protective and Ameliorative Effects of Hydroethanolic Extract of Piper nigrum (L.) Stem against Antiretroviral Therapy-Induced Hepatotoxicity and Dyslipidemia in Wistar Rats.

Antiretroviral therapy (ART) has revolutionized the lives of people living with HIV/AIDS by overall improving their quality of life and increasing life expectancy. However, ART-associated hepatotoxicity and metabolic disorders in HIV/AIDS patients are growing concerns to clinicians, especially due to the long-term use of the drugs. This study reported on the phytochemical and pharmacological profile of hydroethanolic extracts of Piper nigrum stem (PNS) and evaluated its protective effect against tenofovir/lamivudine/efavirenz (TLE)-induced hepatotoxicity and dyslipidemia in Wistar rats. Cytotoxic, antioxidant, and anti-inflammatory assays were performed on PNS. Thirty-six rats divided into 6 groups of 6 animals/group were administered: distilled water, 17 mg/kg TLE, 17 mg/kg TLE and 100 mg/kg silymarin, 17 mg/kg TLE, and Piper extract (200 mg/kg, 400 mg/kg, or 800 mg/kg) orally for 28 days. The body weight of animals was recorded every 7 days. On Day 29, the rats were sacrificed, and blood samples were collected for hematological and biochemical tests. Portions of the liver and kidneys were collected for histological evaluation, while liver homogenates were prepared from the rest to measure antioxidant enzymes. PNS possessed in vitro cytotoxic, antioxidant, and anti-inflammatory activities. A significant decrease (p < 0.05) in the body weight of rats treated with PNS was observed. A significant high platelet count (p < 0.05) was observed in the PNS800 mg/kg group. A considerable decrease in alkaline phosphatase and triglycerides was observed in the silymarin and PNS group compared to the TLE-only group. The findings also show a significant increase in catalase and glutathione in the TLE-only group compared to the normal group, while SOD decreased. Histological observations revealed normal hepatic and renal tissues in the silymarin, and PNS-treated groups compared to the normal control, while leucocyte infiltration was observed in the TLE-only group. These results suggest that PNS extract possessed antioxidant activity that alleviated TLE-induced toxicity. Further studies are necessary to understand the pharmacokinetic interactions between ART and PNS.

Linoleic acid blunts early osteoblast differentiation and impairs oxidative phosphorylation in vitro

BackgroundLinoleic acid (LNA), an essential polyunsaturated fatty acid (PUFA), plays a crucial role in cellular functions. However, excessive intake of LNA, characteristic of Western diets, can have detrimental effects on cells and organs. Human observational studies have shown an inverse relationship between plasma LNA concentrations and bone mineral density. The mechanism by which LNA impairs the skeleton is unclear, and there is a paucity of research on the effects of LNA on bone-forming osteoblasts. MethodsThe effect of LNA on osteoblast differentiation, cellular bioenergetics, and production of oxidized PUFA metabolites in vitro, was studied using primary mouse bone marrow stromal cells (BMSC) and MC3T3-E1 osteoblast precursors. ResultsLNA treatment decreased alkaline phosphatase activity, an early marker of osteoblast differentiation, but had no effect on committed osteoblasts or on mineralization by differentiated osteoblasts. LNA suppressed osteoblast commitment by blunting the expression of Runx2 and Osterix, key transcription factors involved in osteoblast differentiation, and other key osteoblast-related factors involved in bone formation. LNA treatment was associated with increased production of oxidized LNA- and arachidonic acid-derived metabolites and blunted oxidative phosphorylation, resulting in decreased ATP production. ConclusionOur results show that LNA inhibited early differentiation of osteoblasts and this inhibitory effect was associated with increased production of oxidized PUFA metabolites that likely impaired energy production via oxidative phosphorylation.

Systemic effects of hypophosphatasia characterization of two novel variants in the ALPL gene.

Hypophosphatasia (HPP) is an inborn metabolic error caused by mutations in the ALPL gene encoding tissue non-specific alkaline phosphatase (TNSALP) and leading to decreased alkaline phosphatase (ALP) activity. Although the main characteristic of this disease is bone involvement, it presents a great genetic and clinical variability, which makes it a systemic disease. Patients were recruited based on biochemical assessments. Diagnosis was made by measuring serum ALP and pyridoxal 5-phosphate levels and finally by Sanger sequencing of the ALPL gene from peripheral blood mononuclear cells. Characterization of the new variants was performed by transfection of the variants into HEK293T cells, where ALP activity and cellular localization were measured by flow cytometry. The dominant negative effect was analyzed by co-transfection of each variant with the wild-type gene, measuring ALP activity and analyzing cellular localization by flow cytometry. Two previously undescribed variants were found in the ALPL gene: leucine 6 to serine missense mutation (c.17T>C, L6S) affecting the signal peptide and threonine 167 deletion (c.498_500delCAC, T167del) affecting the vicinity of the active site. These mutations lead mainly to non-pathognomonic symptoms of HPP. Structural prediction and modeling tools indicated the affected residues as critical residues with important roles in protein structure and function. In vitro results demonstrated low TNSALP activity and a dominant negative effect in both mutations. The results of the characterization of these variants suggest that the pleiotropic role of TNSALP could be involved in the systemic effects observed in these patients highlighting digestive and autoimmune disorders associated with TNSALP dysfunction. The two new mutations have been classified as pathogenic. At the clinical level, this study suggests that both mutations not only lead to pathognomonic symptoms of the disease, but may also play a role at the systemic level.

Symbiotic can replace zinc bacitracin in diets for layer-type chicks

Context Antibiotics are being prohibited as additives in poultry diets. Therefore, poultry farmers have been searching for other alternatives, such as symbiotics, to include in broilers and laying hens diets. In contrast, symbiotics have not been tested in laying-type chicks, especially symbiotics composed of three groups of bacteria, yeast and two prebiotics. Aim This study examined the effects of replacing zinc bacitracin with symbiotic supplementation on the performance variables, haematology and blood biochemistry variables, and the weight of the immune and digestive systems in layer-type chicks. Methods A total of 1040 female layer-type chicks from 1 to 5 weeks of age were evaluated in a completely randomised design, four treatments and 10 replicates of 26 birds. The treatments consisted of two basal diets (one composed of corn and soybean meal [control diet] and another similar to the first diet, except with the addition of meat and bone meal [MBM]), and two diets based on MBM: one with 0.05% zinc bacitracin (ZnBc) and another with 0.1% symbiotic. Data were subjected to analysis of variance and means were compared by orthogonal contrasts. Key results MBM provided higher mean bodyweight, weight gain and creatinine levels, but lower liver weight, caecum length and gamma-glutamyl transferase levels than in the birds fed the control diet. From 1 to 14 days, ZnBc provided greater bodyweight and weight gain than MBM. From 1 to 28 and 1 to 35 days, ZnBc resulted in higher bodyweight and weight gain, but lower feed intake and feed conversion ratio than birds fed the MBM diet. ZnBc decreased alkaline phosphatase, and increased creatinine levels and gamma-glutamyl transferase. From 1 to 14 and 1 to 21 days, 0.1% symbiotic provided a better feed conversion ratio than in the birds fed the ZnBc diet. The 0.1% symbiotic supplementation resulted in lower liver and fabricius bursa weights, higher mean alkaline phosphatase, and lower globulin, gamma-glutamyl transferase and aspartate transferase levels than ZnBc. Conclusion The symbiotic is effective for female layer type-chicks, fulfilling the purpose of replacing ZnBc. Implications Symbiotics used in chicks’ diets from the first day of life can replace antibiotics to maintain physiological homeostasis and protect them from possible stress situations.

The influence of uremic toxins on low bone turnover disease in chronic kidney disease.

Uremic toxins play a crucial role in the development of low bone turnover disease in chronic kidney disease (CKD) through the induction of oxidative stress. This oxidative stress disrupts the delicate balance between bone formation and resorption, resulting in a decline in both bone quantity and quality. Reactive oxygen species (ROS) activate nuclear factor kappa-B and mitogen-activated protein kinase signaling pathways, promoting osteoclastogenesis. Conversely, ROS hinder osteoblast differentiation by facilitating the binding of Forkhead box O proteins (FoxOs) to β-catenin, triggering apoptosis through FoxOs-activating kinase phosphorylation. This results in increased osteoblastic receptor activator of nuclear factor kappa-B ligand (RANKL) expression and decreased nuclear factor erythroid 2-related factor 2 levels, compromising antioxidant defenses against oxidative damage. As CKD progresses, the accumulation of protein-bound uremic toxins such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS) intensifies oxidative stress, primarily affecting osteoblasts. IS and PCS directly inhibit osteoblast viability, induce apoptosis, decrease alkaline phosphatase activity, and impair collagen 1 and osteonectin, impeding bone formation. They also reduce cyclic adenosine 3',5'-monophosphate (cAMP) production and lower parathyroid hormone (PTH) receptor expression in osteoblasts, resulting in PTH hyporesponsiveness. In summary, excessive production of ROS by uremic toxins not only reduces the number and function of osteoblasts but also induces PTH hyporesponsiveness, contributing to the initiation and progression of low bone turnover disease in CKD.

Justification of The Need to Determine the Level Of 25(OH) D 3 In the Blood Serum of Children to Assess the Quality of Rickitis Prevention

It has been established that the formation of rickets is promoted by a low level of the main metabolite of vitamin D, calcium and phosphorus in the blood serum. This was evidenced by the study of the biochemical parameters of the main indicators of calcium-phosphorus metabolism and the content of 25(OH) D 3 in the examined children before vitamin D prophylaxis when compared with the data of healthy children. Treatment with vitamin D 3 , along with restorative therapy, has significantly increased the effectiveness of preventing rickets. At the same time, there was a decrease in alkaline phosphatase, an increase in the content of 25(OH) D 3 in the blood serum, as well as in the level of calcium and phosphorus.

Effect of the Substrate and Inoculation of Phosphate-Dissolving Bacterial and Fungal with Humic Acids in the Activity of the Alkaline Phosphatase Enzyme in Cadmium-Contaminated Soil

A laboratory experiment was carried out in the laboratories of the Department of Soil Sciences and Water Resources, College of Agriculture, University of Basrah, to identify the role of the bacteria Bacillus subtilis and the fungus Aspergillus niger, with humic acids extracted from fermented cow dung, the effectiveness of the alkaline phosphatase enzyme in soil contaminated with cadmium and compare it with uncontaminated soil. The soil was treated with a cadmium sulfate solution up to the critical limit (3 mg Cd L-1) and humic and fulvic acid were added at a level of 50 L ha-1 separately, leaving the treatment without addition for control. Then the soil was inoculated with bacterial B. subtilis and fungal A. niger isolates individually and with a mixture of isolates, leaving a treatment without inoculation for control, the treatments were incubated at a temperature of 28±2 °C. Different levels of substrate concentration were used (0.010, 0.025, 0.050, 0.075, and 0.100 M). The results showed that cadmium contamination decreased alkaline phosphatase enzyme activity by 12.28%. There was also an increase in the activity of the alkaline phosphatase enzyme at all inoculation treatments compared to the control treatment, with the bio-mixture treatment being superior to the rest of the treatments, reaching 436.944 µg P. nitrophenol gm-1 soil 1 hour-1 in uncontaminated soil and 402.558 µg P. nitrophenol gm-1 soil 1 hour-1 in cadmium contaminated soil. The humic acid treatment showed a similar increase in the activity of the alkaline phosphatase enzyme compared to the control treatment the highest increase was in the fulvic acid treatment. As for the effect of the substrate, the concentration of 0.075 M recorded the highest increase in alkaline phosphatase enzyme activity in unpolluted and cadmium-polluted soil for all treatments.

Yeast polysaccharide supplementation: impact on lactation, growth, immunity, and gut microbiota in Dezhou donkeys.

The Dezhou donkey, a prominent Chinese breed, is known for its remarkable size, rapid growth, and resilience to tough feeding conditions, and disease resistance. These traits are crucial in meeting the growing demand for Ejiao and donkey meat. Yeast polysaccharide (YPS), a functional polysaccharide complex known for its immune-enhancing and growth-promoting properties in livestock and poultry, remains relatively understudied in donkeys. This study aimed to investigate the impact of YPS supplementation on lactating and growing Dezhou donkey jennies and foals. Twelve 45-day-old Dezhou donkey foals and their jennies, matched for body weight and age, were randomly allocated to two dietary groups: a control group receiving a basal diet and an experimental group receiving the basal diet supplemented with 10 g/pen of YPS. The experiment was conducted over a 23-day period, during which donkey foals and lactating jennies were co-housed. The findings revealed that YPS supplementation had no adverse effects on milk production or composition in Dezhou donkey jennies but significantly increased feed intake. Additionally, YPS was associated with increased plasma glucose and creatinine concentrations in foals, while tending to decrease alkaline phosphatase, white blood cell count, red blood cell count, and hemoglobin levels (p < 0.10). Immune indices demonstrated that YPS supplementation elevated the levels of immunoglobulin A (IgA) and immunoglobulin G (IgG) in jennies (p < 0.05) and increased complement component C4 concentrations in foals (p < 0.05). Moreover, YPS positively influenced the fecal microbiome, promoting the abundance of beneficial microorganisms such as Lactobacillus and Prevotella in donkey foals and Terriporobacter and Cellulosilyticum in jennies, all of which contribute to enhanced feed digestion. Additionally, YPS induced alterations in the plasma metabolome for both jennies and foals, with a predominant presence of lipids and lipid-like molecules. Notably, YPS increased the concentrations of specific lipid metabolites, including 13,14-Dihydro PGF2a, 2-Isopropylmalic acid, 2,3-Dinor-TXB2, Triterpenoids, Taurocholic acid, and 3b-Allotetrahydrocortisol, all of which are associated with improved animal growth. In conclusion, this study suggests that dietary supplementation of YPS enhances feed intake, boosts immunity by increasing immunoglobulin levels, stimulates the growth-promoting gut microbiota (Lactobacillus and Prevotella), and exerts no adverse effects on the metabolism of both Dezhou donkey jennies and foals.

Single and combined effects of CuSO4 and polyethylene microplastics on biochemical endpoints and physiological impacts on the narrow-clawed crayfish Pontastacusleptodactylus

This study investigated the toxicity of polyethylene microplastics (MPs; <0.02 mm) and CuSO4, alone and in combination, on the freshwater crayfish Pontastacus leptodactylus. In this study, the crayfish were exposed to PE-MPs (0.0, 0.5, and 1 mg L−1) and CuSO4·5H2O (0.0, 0.5, and 1 mg L−1) for a period of 28 days. Next, multi-biomarkers, including biochemical, immunological, and oxidative stress indicators were analyzed. Results showed that co-exposure to PE-MPs and CuSO4 resulted in increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and decreased alkaline phosphatase (ALP), butyrylcholinesterase (BChE), and gamma-glutamyl-transferase (GGT). Triglycerides, cholesterol, glucose, and albumin content also increased. Although no significant change was observed in lysozyme and phenoloxidase activities in crayfish co-exposed to 0.5 mg L−1 MPs and 0.5 mg L−1 CuSO4, their activities were significantly decreased in other experimental groups. Oxidative stress parameters in hepatopancreas indicated increased superoxide dismutase (SOD), glutathione peroxidase (GPx), and in malondialdehyde (MDA) levels, but decreased catalase (CAT), glucose 6-phosphate dehydrogenase (G6PDH), and cellular total antioxidant (TAC). Results showed that the sub-chronic toxicity of CuSO4 was confirmed. The study confirmed the toxicity of CuSO4 and found that higher concentrations led to more severe effects. Co-exposure to PE-MPs and CuSO4 primarily compromised the endpoints, showing increased toxicity when both pollutants were present in higher concentrations. The activities of POX, LYZ, ALP, GGT, LDH, and CAT were suppressed by both CuSO4 and MPs. However, a synergistic increase was observed in other measured biomarkers in crayfish co-exposed to CuSO4 and MPs.

Therapeutic effect of a new immunotropic composition tested in the model of periodontitis in experimental animals

The article deals with usage of a novel immunotropic drug composition in experimental model of periodontitis. The composition contains silicoorganic glycerogel, exhibits broad spectrum of action upon the etiological pathogen. A good therapeutic effect was revealed by clinical, laboratory and histological criteria. Histology showed absence of osteoclasts, reduced lacunas, higher density and normalization of tissue structures, recovery of microcirculation, angiogenesis and formation of granulation tissues. However, the phosphorus-to-calcium ratio in the group supplied with peroral vitamin D treatment, was characterized by significant decrease in alkaline phosphatase and inorganic phosphorus thus confirming efficiency of complex topical effect of the given composition and vitamin D.

Phytochemical composition, toxicological profiling and effect on pup birth weight of Corchorus olitorius leaf extract in rats: Implications for fetal macrosomia control

Ethnopharmacological relevanceCorchorus olitorius is used in ethnomedicine to arrest threatened miscarriage, ease labour, and promote smooth childbirth. Aim of the studyTo evaluate the phytochemical composition, toxicity profile, and effect of Corchorus olitorius L. leaf extract (COLE) on fetal macrosomia control in rats. Materials and methodsThe chemical constituents of COLE were determined using gas chromatography-mass spectrometry (GC-MS). A single dose of up to 5000 mg/kg was administered in the acute toxicity test, and the rats were monitored for 14 days. In the sub-acute toxicity study, rats were treated with the extract for 28 days, and liver function, renal function, lipid profile, and serum antioxidant parameters, coupled with liver and kidney histology, were used to assess the toxicity potential of the extract. In the pup birth weight study, treatment of pregnant rats lasted until the birth of pups and continued for an extra 4 weeks. Rats in group 1 served as a control, whereas rats in groups 2, 3, and 4 received daily doses of 200, 400, and 800 mg/kg body weight of COLE, respectively, via oral gavage. ResultsBioactive compounds such as D-limonene, phytol, hexadecanoic acid, 9-octadecenoic acid (Z), dodecanoic acid, and ethyl 9,12,15-octadecatrienoate with well-known pharmacological activities were detected. LD50 of COLE was >5000 mg/kg. COLE decreased body weight and increased red blood cell, packed cell volume, and haemoglobin values when compared with the control (p < 0.05). COLE significantly decreased alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase but did not cause any significant (p > 0.05) changes in other biochemical (liver and kidney) parameters when compared to control. COLE decreased total cholesterol, triglycerides, low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol when compared with the control (p < 0.05). Birth weights of pups were significantly decreased in the COLE-treated groups when compared with the control (p < 0.05), but the observed difference terminated by the fourth week of weaning. ConclusionThe results showed that COLE is not toxic but has several bioactive compounds with known pharmacological activities and therefore may be a safe oral agent for fetal macrosomia control.

Вплив різних доз цитратів наночастинок йоду, селену, сірки на активність гіпофіз-тиреоїдної системи і обмін речовин у щурів

The use of organic compounds of iodine, selenium, and sulfur is limited due to the complexity of their chemical synthesis. The latest nanotechnological methods of obtaining organic compounds I, Se, S provide the opportunity to replace their mineral and organic salts with citrate mixtures synthesized on the basis of nanotechnology. This provides a perspective for the use of nanocomposition citrates I, Se, S in biology, medicine and animal husbandry. The research aimed to determine the effect of different doses of I, Se, S nanoparticles citrates on the activity of the pituitary-thyroid system and metabolism in the blood of male rats. The animals of the experimental groups received daily with water a mixture of I, Se, S in experimentally determined ratios (3:1:5) by mass of elements and doses, according to the concentration of iodine in μg/kg of body weight: 1–2.4 (low); 2–24 (average); 3–240 (high); 4–2400 (toxic). Blood for laboratory studies was taken on the 40th day of drinking I, Se, S after the decapitation of animals. The content of thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), thyroglobulin (Tg), antibodies to thyroglobulin (Anti-Tg) and thyroperoxidase (Anti-TPO), as well as hematological and biochemical indicators characterizing the activity of physiological systems of the body, were determined in the blood. Activation of the body’s immune system was established with an increase in the number of monocytes in the blood of rats of the experimental groups under the influence of all applied doses of I, Se, S, and platelets – only in doses of 2.4, 24, and 240 μg of iodine. The effect of the toxic dose led to an increase in the number of leukocytes in the blood of animals of the 4 group, with a decrease in platelets. A probable decrease in the relative level of lymphocytes and an increase in monocytes in the blood of rats in the experimental groups characterized changes in the leukogram of blood. The applied doses of I, Se, S stimulated the synthesis of cholesterol and the influx of calcium into the peripheral blood of rats of the experimental groups. Still, they inhibited the activity of alkaline phosphatase and the creatinine content. The toxic effect of I, Se, S nanoparticles citrates in a dose of 2400 μg of I led to a significant increase in the activity of aminotransferases and a decrease in alkaline phosphatase, phosphorus level, and body weight in rats. The effect of high and toxic doses of I, Se, S nanoparticles citrates on the functioning of the pituitary-thyroid system led to a decrease in the concentration of TSH, T3, T4, and Tg against the background of an increase in Anti-TPO and Anti-Tg in the blood serum of rats of experimental groups.

GATA4 inhibits odontoblastic differentiation of dental pulp stem cells through targeting IGFBP3

ObjectiveThe odontogenic differentiation of human dental pulp stem cells (HDPSCs) is associated with reparative dentinogenesis. Transcription factor GATA binding protein 4 (GATA4) is proved to be essential for osteoblast differentiation and bone remodeling. This study clarified the function of GATA4 in HDPSCs odontoblast differentiation. MethodsThe change in GATA4 expression during reparative dentin formation was detected by immunohistochemistry staining. The expression of GATA4 during HDPSCs odontoblastic differentiation was detected by western blot and quantitative polymerase chain reaction. The effect of GATA4 on odontoblast differentiation was investigated following overexpression lentivirus transfection. RNA sequencing, dual luciferase assay and chromatin immunoprecipitation (CHIP) were conducted to verify downstream targets of GATA4. GATA4 overexpression lentivirus and small interference RNA targeting IGFBP3 were co-transfected to investigate the regulatory mechanism of GATA4. ResultsUpregulated GATA4 was observed during reparative dentin formation in vivo and the odontoblastic differentiation of HDPSCs in vitro. GATA4 overexpression suppressed the odontoblastic potential of HDPSCs, demonstrated by decreased alkaline phosphatase activity (p < 0.0001), mineralized nodules formation (p < 0.01), and odonto/osteogenic differentiation markers levels (p < 0.05). RNA sequencing revealed IGFBP3 was a potential target of GATA4. CHIP and dual luciferase assays identified GATA4 could activate IGFBP3 transcription. Additionally, IGFBP3 knockdown recovered the odontoblastic differentiation defect caused by GATA4 overexpression (p < 0.05). ConclusionsGATA4 inhibited odontoblastic differentiation of HDPSCs via activating the transcriptional activity of IGFBP3, identifying its promising role in regulating HDPSCs odontoblast differentiation and reparative dentinogenesis.

Impact of vitamin D supplementation on markers of bone turnover: Systematic review and meta-analysis of randomised controlled trials.

The effects of vitamin D administration on bone turnover markers (BTMs) in adults are controversial. Thus, we carried out a meta-analysis of available randomised controlled trials (RCTs) to examine the impact of vitamin D supplementation on BTMs. To identify relevant RCTs, we searched the PubMed/MEDLINE, Web of Science, Scopus, Cochrane Library and Embase databases for manuscripts published up to July 2022. The present study was conducted in agreement with the PRISMA guidelines. Weighed mean difference (WMD) and 95% confidence intervals (CI) were used to calculate the magnitude of the effect of the intervention. A total of 42 RCTs were included in the meta-analysis. The age of the participants enrolled in the RCTs ranged from 19.4 to 84 years. The pooled results depicted a decrease in deoxypyridinoline (DPD) concentrations (WMD: -1.58 nmol/mmol, 95% CI: -2.55, -.61, p = .001) following vitamin D supplementation. In addition, subgroup analyses demonstrated that vitamin D administration notably reduced procollagen type I N-terminal propeptide (PINP) levels in individuals aged >50 years and led to a pronounced decrease in alkaline phosphatase (ALP) values when the intervention lasted >12 weeks. No significant effect was observed on other BTMs, for example, collagen type 1 cross-linked C-telopeptide (CTX) and osteocalcin (OC) levels. Vitamin D administration decreases DPD, PINP and ALP levels, indicating a reduced bone turnover following the intervention. Other BTMs, for example, CTX or OC values, were not affected by vitamin D prescription. Vitamin D supplementation may exert a positive effect on some important BTMs.