Promoting longevity in aged liver through NLRP3 inflammasome inhibition using tauroursodeoxycholic acid (TUDCA) and SCD probiotics.

This investigation explores the combined influence of SCD Probiotics and tauroursodeoxycholic acid (TUDCA) on liver health in elderly male Sprague-Dawley rats. Through the administration of intravenous TUDCA (300 mg/kg) and oral SCD Probiotics (3 mL at 1 × 10^8 CFU) daily for one week, this study evaluates the biomolecular composition, histopathological alterations, and inflammasome activity in the liver. Analytical methods encompassed ATR-FTIR spectroscopy integrated with machine learning for the assessment of biomolecular structures, RT-qPCR for quantifying inflammasome markers (NLRP3, ASC, Caspase-1, IL18, IL1ß), and histological examinations to assess liver pathology. The findings reveal that TUDCA prominently enhanced lipid metabolism by reducing cholesterol esters, while SCD Probiotics modulated both lipid and protein profiles, notably affecting fatty acid chain lengths and protein configurations. Histological analysis showed significant reductions in cellular degeneration, lymphatic infiltration, and hepatic fibrosis. Furthermore, the study noted a decrease in the immunoreactivity for NLRP3 and ASC, suggesting suppressed inflammasome activity. While SCD Probiotics reduced the expression of certain inflammasome-related genes, they also paradoxically increased AST and LDH levels. Conversely, an exclusive elevation in albumin levels was observed in the group treated with SCD Probiotics, implying a protective role against liver damage. These results underscore the therapeutic potential of TUDCA and SCD Probiotics for managing age-associated liver disorders, illustrating their individual and synergistic effects on liver health and pathology. This study provides insights into the complex interactions of these agents, advocating for customized therapeutic approaches to combat liver fibrosis, enhance liver functionality, and decrease inflammation in aging populations.

Supplementing probiotics during intermittent fasting proves more effective in restoring ileum and colon tissues in aged rats.

This study aimed to explore the impact of SCD Probiotics supplementation on biomolecule profiles and histopathology of ileum and colon tissues during a 30-day intermittent fasting (IF) program. Male Sprague-Dawley rats, aged 24 months, underwent 18-h daily fasting and received 3 mL (1 × 108 CFU) of SCD Probiotics. The differences in biomolecule profiles were determined using FTIR Spectroscopy and two machine learning techniques, Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM), which showed significant differences with high accuracy rates. Spectrochemical bands indicating alterations in lipid, protein and nucleic acid profiles in both tissues. The most notable changes were observed in the group subjected to both IF and SCD Probiotics, particularly in the colon. Both interventions, individually and in combination, decreased protein carbonylation levels. SCD Probiotics exerted a more substantial impact on membrane dynamics than IF alone. Additionally, both IF and SCD Probiotics were found to have protective effects on intestinal structure and stability by reducing mast cell density and levels of TNF-α and NF-κB expression in ileum and colon tissues, thus potentially mitigating age-related intestinal damage and inflammation. Furthermore, our results illustrated that while IF and SCD Probiotics individually instigate unique changes in ileum and colon tissues, their combined application yielded more substantial benefits. This study provides evidence for the synergistic potential of IF and SCD Probiotics in combating age-related intestinal alterations.

Reduced liver damage and fibrosis with combined SCD Probiotics and intermittent fasting in aged rat.

This study aimed to examine the impact of SCD Probiotics supplementation on liver biomolecule content and histological changes during a 30-day intermittent fasting (IF) program in 24-month-old male Sprague-Dawley rats. Rats underwent 18-h daily fasting and received 1 × 108 CFU of SCD Probiotics daily. Liver tissue biomolecules were analysed using FTIR Spectroscopy, LDA, and SVM techniques, while histopathological evaluations used Haematoxylin and eosin and Masson trichrome-stained tissues. Blood samples were collected for biochemical analysis. Gross alterations in the quantity of biomolecules were observed with individual or combined treatments. LDA and SVM analyses demonstrated a high accuracy in differentiating control and treated groups. The combination treatments led to the most significant reduction in cholesterol ester (1740 cm-1 ) and improved protein phosphorylation (A1239 /A2955 and A1080 /A1545 ) and carbonylation (A1740 /A1545 ). Individually, IF and SCD Probiotics were more effective in enhancing membrane dynamics (Bw2922 /Bw2955 ). In treated groups, histological evaluations showed decreased hepatocyte degeneration, lymphocyticinfiltration, steatosis and fibrosis. Serum ALP, LDH and albumin levels significantly increased in the SCD Probiotics and combined treatment groups. This study offers valuable insights into the potential mechanisms behind the beneficial effects of IF and SCD Probiotics on liver biomolecule content, contributing to the development of personalized nutrition and health strategies.

SCD Probiotics mitigate cafeteria diet-induced liver damage in Wistar rats during development.

BACKGROUND AND AIM: The liver plays a critical role in metabolic homeostasis, and its health is often compromised by poor dietary habits. This study aimed to investigate the therapeutic potential of SCD Probiotics in mitigating adverse liver effects induced by a cafeteria diet in male Wistar rats during their developmental period. METHODS: Four groups of seven male Wistar rats each were subjected to different dietary regimens from day 21 (weaning) to day 56. The groups were as follows: a control group on normal feed; a probiotic-supplemented group on normal feed; a group on a cafeteria diet mixed with normal feed; and a group on a cafeteria diet mixed with normal feed, supplemented with SCD Probiotics. Liver health was assessed using Fourier transform infrared spectroscopy and histopathological evaluations. RESULTS: Rats on the cafeteria diet exhibited significant disruptions in lipid, protein, cholesterol, triglyceride levels, and glycogen/phosphate content. Histopathological abnormalities such as lymphocytic infiltration, steatosis, and necrosis were also observed. However, SCD Probiotics supplementation led to notable improvements in the liver's biomolecular composition and mitigated histopathological abnormalities. Serum liver enzyme levels (AST, ALT, ALP, and LDH) also showed beneficial effects, while serum albumin levels remained stable. CONCLUSIONS: SCD Probiotics demonstrated a promising potential to counteract the adverse liver effects induced by a cafeteria diet in male Wistar rats. The study revealed significant improvements in biomolecular composition, histopathology, and serum enzyme levels. However, these findings are preliminary and necessitate further in vivo studies and clinical trials for validation.

The rejuvenating influence of young plasma on aged intestine.

This study aims to investigate the effects of plasma exchange on the biomolecular profiles and histology of ileum and colon tissues in young and aged Sprague-Dawley male rats. Fourier transform infrared (FTIR) spectroscopy, linear discriminant analysis and support vector machine (SVM) techniques were employed to analyse the lipid, protein, and nucleic acid indices in young and aged rats. Following the application of young plasma, aged rats demonstrated biomolecular profiles similar to those of their younger counterparts. Histopathological and immunohistochemical assessments showed that young plasma had a protective effect on the intestinal tissues of aged rats, increasing cell density and reducing inflammation. Additionally, the expression levels of key inflammatory mediators tumour necrosis factor-alpha and cyclooxygenase-2 significantly decreased after young plasma administration. These findings underscore the therapeutic potential of young plasma for mitigating age-related changes and inflammation in the intestinal tract. They highlight the critical role of plasma composition in the ageing process and suggest the need for further research to explore how different regions of the intestines respond to plasma exchange. Such understanding could facilitate the development of innovative therapies targeting the gastrointestinal system, enhancing overall health during ageing.

Age-related differences in response to plasma exchange in male rat liver tissues: insights from histopathological and machine-learning assisted spectrochemical analyses.

This study aimed to examine the biological effects of blood plasma exchange in liver tissues of aged and young rats using machine learning methods and spectrochemical and histopathological approaches. Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM) were the machine learning algorithms employed. Young plasma was given to old male rats (24 months), while old plasma was given to young male rats (5 weeks) for thirty days. LDA (95.83-100%) and SVM (87.5-91.67%) detected significant qualitative changes in liver biomolecules. In old rats, young plasma infusion increased the length of fatty acids, triglyceride, lipid carbonyl, and glycogen levels. Nucleic acid concentration, phosphorylation, and carbonylation rates of proteins were also increased, whereas a decrease in protein concentration was measured. Aged plasma decreased protein carbonylation, triglyceride, and lipid carbonyl levels. Young plasma infusion improved hepatic fibrosis and cellular degeneration and reduced hepatic microvesicular steatosis in aged rats. Otherwise, old plasma infusion in young rats caused disrupted cellular organization, steatosis, and increased fibrosis. Young plasma administration increased liver glycogen accumulation and serum albumin levels. Aged plasma infusion raised serum ALT levels while diminished ALP concentrations in young rats, suggesting possible liver dysfunction. Young plasma increased serum albumin levels in old rats. The study concluded that young plasma infusion might be associated with declined liver damage and fibrosis in aged rats, while aged plasma infusion negatively impacted liver health in young rats. These results imply that young blood plasma holds potential as a rejuvenation therapy for liver health and function.

Role of age-related plasma in the diversity of gut bacteria.

Recent studies have demonstrated the efficacy of young blood plasma factors in reversing aging-related deformities. However, the impact of plasma exchange between young and old individuals on gut microbiota remains understudied. To investigate this, we evaluated the effects of plasma exchange between 5-week-old and 24-month-old rats on gut microbiota composition. In this study, old rats were administered 0.5 ml of young plasma, while young rats were administered 0.25 ml of old plasma daily for 30 days. Metagenome analysis was performed on the contents of the cecum after completing plasma transfer. Results showed that transferring young plasma to old rats significantly increased the alpha diversity indices (Shannon and Simpson values), while the Firmicutes to Bacteroidetes ratio decreased significantly. Conversely, transferring aged plasma to young rats led to a significant decrease in Shannon value and F/B ratio but no change in Simpson value. Plasma exchange also caused substantial changes in the top ten dominant genera and species found in the gut microbiota of young and old rats. After young blood plasma transfer, the dominant bacterial profile in the old gut microbiota shifted toward the bacterial profile found in the young control group. Notably, old plasma also altered the gut microbiota structure of young rats toward that of old rats. Our findings suggest that age-related changes in plasma play a crucial role in gut microbiota species diversity and their presence rates.

Intermittent fasting supports the balance of the gut microbiota composition / El ayuno intermitente favorece el equilibrio de la composición de la microbiota intestinal

There is a growing body of detailed research demonstrating that intermittent fasting is essentially a cleansing activity in terms of health. Especially since its applications that exceed 16 h trigger autophagy, it continues its effect on all tissue and organ systems after the regeneration movement that starts at the cellular level. Similarly, it continues to be better understood with each passing day that the gut microbiota (GM) has many positive effects on all tissue and organ systems. Although the GM is affected by many different parameters, dietary habits are reported to be the most effective factor. Therefore, it is important to investigate the effects of different preferred fasting practices on the GM, which has numerous health benefits. Pointing out this situation, this study aims to determine the effects of 18-h intermittent fasting for 5 weeks on the shaping of GM. A 12-month-old male Wistar rat was chosen as the model organism in the study. At the end of the application, the metagenome was applied to the cecum content of the intestinal tissue collected from the sacrificed animals. Intermittent fasting practice led to an increase in alpha diversity, which expresses a significant bacterial diversity, the stabilization of Firmicutes and Bacteroidetes ratios (F/B), and the reshaping of the values with the highest prevalence in all stages of the classification, especially in the family, genus, and species care. Analysis results showed that the preferred intermittent fasting program helps balance the GM composition. This study is an important example showing the strong positive link between intermittent fasting and GM.(AU)

Intermittent fasting supports the balance of the gut microbiota composition.

There is a growing body of detailed research demonstrating that intermittent fasting is essentially a cleansing activity in terms of health. Especially since its applications that exceed 16 h trigger autophagy, it continues its effect on all tissue and organ systems after the regeneration movement that starts at the cellular level. Similarly, it continues to be better understood with each passing day that the gut microbiota (GM) has many positive effects on all tissue and organ systems. Although the GM is affected by many different parameters, dietary habits are reported to be the most effective factor. Therefore, it is important to investigate the effects of different preferred fasting practices on the GM, which has numerous health benefits. Pointing out this situation, this study aims to determine the effects of 18-h intermittent fasting for 5 weeks on the shaping of GM. A 12-month-old male Wistar rat was chosen as the model organism in the study. At the end of the application, the metagenome was applied to the cecum content of the intestinal tissue collected from the sacrificed animals. Intermittent fasting practice led to an increase in alpha diversity, which expresses a significant bacterial diversity, the stabilization of Firmicutes and Bacteroidetes ratios (F/B), and the reshaping of the values with the highest prevalence in all stages of the classification, especially in the family, genus, and species care. Analysis results showed that the preferred intermittent fasting program helps balance the GM composition. This study is an important example showing the strong positive link between intermittent fasting and GM.

Young plasma transfer recovers decreased sperm counts and restores epigenetics in aged testis.

BACKGROUND AND AIM: Aging is one of the causes of male infertility, and abnormal global DNA methylation and imprinting defects have been characterized in testis during biological aging. One of the important emerging approaches aims to take advantage of the healing properties of young blood plasma to limit the progression of aging in various organs in the body. We aimed to show whether blood plasma transfer has an effect on DNA methylation and spermatogenetic cell development. In addition, we aimed to show whether the young plasma transfer to old mice has an effect on the rejuvenation of the old and whether the impaired DNA methylation and PCNA expression in old age can be restored. METHODS: Groups were (i) young control, (ii) young plasma transfer to aged, (iii) aged control, (iv) aged plasma transfer to young. We utilized IHC and WB in protein level of Dnmts. For the global DNA methylation level, we used 5-methylcytosine staining. We also analyzed PCNA protein expressions in all groups by IHC. RESULTS: We found that transfusion of young plasma into the old animal restored DNA methylation and PCNA expression as it did in the young animal. Most importantly, we observed an increase in spermatogonia and spermatid counts in older animals after young blood plasma transfer. CONCLUSIONS: Our findings show that young plasma transfer can restore epigenetic disorders that occur with aging and solve infertility problems by increasing the sperm count that decreases. It needs to be supported by different studies, especially human studies.

The effect of young blood plasma administration on gut microbiota in middle-aged rats.

Numerous in-depth studies continue to reveal the many benefits of gut microbiota and young blood plasma administration. Dysbiosis, which occurs in the intestinal microbiota, especially in the aging process, is associated with many metabolic and cognitive disorders. Therefore, many studies aim to reverse the dysbiosis that occurs. There are also studies showing that young blood plasma application reverses the effects of aging at the level of many tissues and organs. Today, while research continues to reveal all the benefits of young blood plasma application in terms of health, blood plasma centers are also being established. In this study, we aimed to reveal the impact of young blood plasma, administered for 1 month, on the intestinal microbiota of middle-aged rats. After detailed metagenome analysis, alpha diversity indices demonstrated greater bacterial richness in the microbiota of plasma-administered rats compared with control rats. In addition, the Firmicutes/Bacteroidetes ratio was significantly diminished in plasma group microbiota, confirming possible rejuvenation properties of young plasma. Furthermore, increased counts of Bifidobacterium longum, Coprococcus catus, and Romboutsia ilealis species were measured in plasma-administered rats. The study revealed many fluctuations in different bacterial taxonomic units of the microbiota that could be valuable in future research on blood-based anti-aging treatments.

Intermittent fasting-induced biomolecular modifications in rat tissues detected by ATR-FTIR spectroscopy and machine learning algorithms.

This study aimed to reveal the intermittent fasting-induced alterations in biomolecules of the liver, ileum, and colon tissues of rats using Support Vector Machine (SVM) and Linear Discriminant Analysis (LDA) algorithms developed on infrared spectrochemical data. LDA prediction accuracies were generally calculated in the range of 95-100%, while training and validation accuracies of SVM were in the range of 91-100% and 83-91%, respectively. The quantitative measurements of spectral bands at the CH (lipids), Amide (proteins), and PO2 antisymmetric (nucleic acids) stretching regions were performed to monitor modulated metabolic processes. The concentration of biomolecules and phosphorylation rate of proteins were found higher in studied tissues. The altered conformations and low rates of carbonylation (oxidation) were also common in proteins. No significant change was recorded for the length of fatty acid acyl chains (A2922/A2955 band area ratio) in the liver, whereas the shortening of acyl chains was calculated as 23% and 27% in ileum and colon tissues, respectively. Enhanced membrane dynamics (Bw2922/Bw2955 bandwidth ratio) were depicted in the liver (35% increase), while a decline in dynamics was apparent in the ileum (36% decrease) and colon (31% decrease). The study revealed important alterations in major biomolecules of studied tissues.

Infrared spectrochemical findings on intermittent fasting-associated gross molecular modifications in rat myocardium.

Cardiovascular diseases are among the primary life-threatening conditions affecting human society. Intermittent fasting is shown to be functional in the prevention of cardiovascular diseases, however, the information on fasting-associated modifications in myocardial biomolecules is limited. This study aimed to determine the impact of 18-h intermittent fasting administered for five weeks on 12 months-old rats using supervised linear discriminant analysis and support vector machine algorithms constructed on spectrochemical data obtained from myocardial tissues. These algorithms revealed gross biomolecular modifications, while quantitative analyses demonstrated higher amounts of saturated lipids (19%), triglycerides (11%), and lipids (56%), in addition to enhancement in membrane dynamics (18%). The concentrations of nucleic acids and glucose are increased by 52%, while the glycogen content is diminished by 61%. The protein carbonylation/oxidation is reduced by 38%, whereas a 35% increase in protein content was measured. Phosphorylated proteins have been calculated to be at higher concentrations in the 13-62% range. The study findings demonstrated significant molecular changes in the myocardium of rats subjected to intermittent fasting.

The effects of repeated antibiotic administration to juvenile BALB/c mice on the microbiota status and animal behavior at the adult age.

Recent studies carried on germ -free (GF) animal models suggest that the gut microbiota (GM) may play a role in the regulation of anxiety, mood, and cognitive abilities such as memory and learning processes. Consistently, any treatment disturbing the gut microbiota, including the overuse of antibiotics, may influence the brain functions and impact behavior. In the present study, to address this issue, two wide-spectrum antibiotics (ampicillin and cefoperazone, 1 g/l) were repeatedly applied throughout a 6-week period to initially 21-day-old male BALB/c mice. Antibiotics were administered separately or in a mixed fashion. On the completion of the antibiotic treatment, all mice were subjected to the behavioral tests. The serum levels of corticosterone and brain-derived neurotropic factor (BDNF) were assessed. Gut microbiota profiles were obtained by using denaturing gradient gel electrophoresis system, DGGE, from fecal samples. Ampicillin had a greater impact on both, gut microbiota composition and mice behavior compared to cefoperazone. All antibiotic-treated groups manifested a decrease in the locomotor activity and reduced recognition memory. However, the ampicillin-treated groups showed a higher anxiety level as assessed by the open field and the elevated plus maze tests and an increased immobility (behavioral despair) in the forced swim test. Obtained results evidently show that in mice, a repeated antibiotic treatment applied during adolescence, parallel to the changes in GM, affects locomotor activity, affective behavior and cognitive skills in young adults with ampicillin specifically enhancing anxiety- and depressive-like responses. Lower levels of serum BDNF were not associated with cognitive impairment but with changes in affective-like behaviors. Repeated administration of neither ampicillin nor cefoperazone affected basal serum corticosterone levels. This is one of the few studies demonstrating changes in a behavioral phenotype of young-adult subjects who were previously exposed to a repeated antibiotic treatment.

Bone marrow mesenchymal stem cell donors with a high body mass index display elevated endoplasmic reticulum stress and are functionally impaired.

Bone marrow mesenchymal stem cells (BM-MSCs) are promising candidates for regenerative medicine purposes. The effect of obesity on the function of BM-MSCs is currently unknown. Here, we assessed how obesity affects the function of BM-MSCs and the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) therein. BM-MSCs were obtained from healthy donors with a normal (<25) or high (>30) body mass index (BMI). High-BMI BM-MSCs displayed severely impaired osteogenic and diminished adipogenic differentiation, decreased proliferation rates, increased senescence, and elevated expression of ER stress-related genes ATF4 and CHOP. Suppression of ER stress using tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyrate (4-PBA) resulted in partial recovery of osteogenic differentiation capacity, with a significant increase in the expression of ALPL and improvement in the UPR. These data indicate that BMI is important during the selection of BM-MSC donors for regenerative medicine purposes and that application of high-BMI BM-MSCs with TUDCA or 4-PBA may improve stem cell function. However, whether this improvement can be translated into an in vivo clinical advantage remains to be assessed.