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BMC Gastroenterology Jun 2024Inflammatory bowel disease (IBD), a chronic inflammatory condition, is caused by several factors involving aberrant immune responses. Genetic factors are crucial in IBD...
BACKGROUND
Inflammatory bowel disease (IBD), a chronic inflammatory condition, is caused by several factors involving aberrant immune responses. Genetic factors are crucial in IBD occurrence. Mendelian randomization (MR) can offer a new perspective in understanding IBD's genetic background.
METHODS
Single nucleotide polymorphisms (SNPs) were considered instrumental variables (IVs). We analyzed the relationship between 731 immunophenotypes, 1,400 metabolite phenotypes, and IBD. The total effect was decomposed into indirect and direct effects, and the ratio of the indirect effect to the total effect was calculated.
RESULTS
We identified the causal effects of HLA-DR-expressing CD14 + monocytes on IBD through MR analysis. The phenotype "HLA-DR expression on CD14 + monocytes" showed the strongest association among the selected 48 immune phenotypes. Chiro-inositol metabolites mediated the effect of CD14 + monocytes expressing HLA-DR on IBD. An increase in Chiro-inositol metabolites was associated with a reduced risk of IBD occurrence, accounting for 4.97%.
CONCLUSION
Our findings revealed a new pathway by which HLA-DR-expressing CD14 + monocytes indirectly reduced the risk of IBD occurrence by increasing the levels of Chiro-inositol metabolites. The results provided a new perspective on the immunoregulatory mechanisms underlying IBD, laying a theoretical foundation for developing new therapeutic targets in the future.
Topics: Humans; Monocytes; Lipopolysaccharide Receptors; Inflammatory Bowel Diseases; HLA-DR Antigens; Polymorphism, Single Nucleotide; Inositol; Mendelian Randomization Analysis; Phenotype; Immunophenotyping; Female; Male
PubMed: 38886630
DOI: 10.1186/s12876-024-03271-2 -
Scientific Reports Jun 2024Crocin is a carotenoid compound in saffron with anti-cancer properties. However, its therapeutic application is limited by its low absorption, bioavailability, and...
Crocin is a carotenoid compound in saffron with anti-cancer properties. However, its therapeutic application is limited by its low absorption, bioavailability, and stability, which can be overcome through nanocarrier delivery systems. This study used surface-modified Nano-crystalline cellulose (NCC) to deliver crocin to cancer cells. NCC modified with CTAB were loaded with crocin and then conjugated with folic acid (NCF-CR-NPs). The synthesized nanoparticles (NPs) were characterized using FTIR, XRD, DLS, and FESEM. The crystallinity index of NCC was 66.64%, higher than microcrystalline cellulose (61.4%). The crocin loading and encapsulation efficiency in NCF-CR-NPs were evaluated. Toxicity testing by MTT assay showed that NCF-CR-NPs had higher toxicity against various cancer cell lines, including colon cancer HT-29 cells (IC50 ~ 11.6 μg/ml), compared to free crocin. Fluorescent staining, flow cytometry, and molecular analysis confirmed that NCF-CR-NPs induced apoptosis in HT-29 cells by increasing p53 and caspase 8 expression. The antioxidant capacity of NCF-CR-NPs was also evaluated using ABTS and DPPH radical scavenging assays. NCF-CR-NPs exhibited high free radical scavenging ability, with an IC50 of ~ 46.5 μg/ml for ABTS. In conclusion, this study demonstrates the potential of NCF-CR-NPs to deliver crocin to cancer cells effectively. The NPs exhibited enhanced anti-cancer and antioxidant activities compared to free crocin, making them a promising nanocarrier system for crocin-based cancer therapy.
Topics: Carotenoids; Folic Acid; Humans; Cellulose; Nanoparticles; Apoptosis; Antineoplastic Agents; HT29 Cells; Drug Carriers; Antioxidants; Cell Line, Tumor; Drug Delivery Systems; Cell Survival
PubMed: 38886450
DOI: 10.1038/s41598-024-64758-2 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2024To study the clinical and neurophysiological features of children with low cognitive tempo (NCT), as well as the effectiveness of the drug Pantogam in the treatment of...
OBJECTIVE
To study the clinical and neurophysiological features of children with low cognitive tempo (NCT), as well as the effectiveness of the drug Pantogam in the treatment of this pathology.
MATERIAL AND METHODS
A total of 90 children aged 8 to 10 years were examined. Of these, the main study group consisted of 30 children with NCT, the comparison group consisted of 30 children with a combined type of attention deficit hyperactivity disorder ADHD (ADHD-K), the control group consisted of 30 children without neuropsychiatric disorders. The study used clinical, neurophysiological (electroencephalography (EEG)) and parametric methods. The CMAS scale of apparent anxiety (The Children's Form of Manifest Anxiety Scale), the SNAP-IY scale (assessment of the degree of inattention, hyperactivity and impulsivity), the TOVA computer test (the Test of Variables of Attention), the scale «SCT» (Sluggish Cognitive Tempo) for assessing manifestations of low cognitive tempo, the «RAM» technique for quantifying working memory. Pantogam was used to treat patients at a dose of 750 mg per day for 8 weeks.
RESULTS
Patients with NCT are characterized by more pronounced attention disorders compared with healthy peers and with children with ADHD-K, and they have a decrease in mainly not selective attention, but the overall level of functional activity. Also, the group of children with NCT has an increased level of anxiety compared to the group of children with ADHD. A comparative analysis of the level of impulsivity showed that children with NCT are less characterized by a deficit in inhibition processes. According to the quantitative analysis of the EEG, specific changes in functional activity in the frontal and central regions of the cerebral cortex were revealed (a statistically significant increase in the ratio of absolute theta rhythm to beta1 rhythm, compared with other groups), reflecting insufficient cortical arousal and less focused neural states. When re-evaluating the condition of children with NCT after a course of therapy with Pantogam, an improvement in the form of a decrease in the degree of inattention, the severity of memory impairment and a decrease in reaction time was recorded in 60% of cases. According to quantitative EEG analysis, there was a significant decrease in the ratio of absolute theta rhythm to beta1 rhythm in the central leads of both hemispheres and in the parietal-temporal leads of the left hemisphere, indicating an increase in the level of overall activation of the cerebral cortex after a course of treatment.
CONCLUSION
Clinical and neurophysiological differences were revealed in patients with NCT and with combined ADHD. It has been shown that the use of Pantogam for the treatment of children with NCT leads not only to a decrease in the main manifestations of this disorder, but also to an improvement in the functional state of the brain.
Topics: Humans; Child; Attention Deficit Disorder with Hyperactivity; Male; Female; Electroencephalography; Pantothenic Acid; Cognition; Attention; Memory, Short-Term; gamma-Aminobutyric Acid
PubMed: 38884438
DOI: 10.17116/jnevro2024124051120 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2024Various diseases of the peripheral nervous system are associated with metabolic disorders of B vitamins. A lack of neurotropic vitamins, which began in the early stages... (Review)
Review
Various diseases of the peripheral nervous system are associated with metabolic disorders of B vitamins. A lack of neurotropic vitamins, which began in the early stages of the development of a bacterial disease, led to its more rapid development. The article analyzes data on B vitamin deficiency in the pathogenesis of the most dangerous diseases of the peripheral nervous system. Information is provided about the dangers of the clinical use of the drug Combilipen for the treatment of such patients.
Topics: Humans; Vitamin B Complex; Peripheral Nervous System Diseases; Vitamin B Deficiency
PubMed: 38884433
DOI: 10.17116/jnevro202412405175 -
Frontiers in Immunology 2024SLE is a complex autoimmune disease with deleterious effects on various organs. Accumulating evidence has shown abnormal vitamin B12 and one-carbon flux contribute to...
BACKGROUND
SLE is a complex autoimmune disease with deleterious effects on various organs. Accumulating evidence has shown abnormal vitamin B12 and one-carbon flux contribute to immune dysfunction. Transcobalamin II (TCN2) belongs to the vitamin B12-binding protein family responsible for the cellular uptake of vitamin B12. The role of TCN2 in SLE is still unclear.
METHODS
We collected clinical information and blood from 51 patients with SLE and 28 healthy controls. RNA sequencing analysis, qPCR, and western blot confirmed the alteration of TCN2 in disease monocytes. The correlation between TCN2 expression and clinical features and serological abnormalities was analyzed. TCN2 heterozygous knockout THP1 cells were used to explore the effects of TCN2 dysfunction on monocytes. CCK-8 assay and EdU staining were used to detect cell proliferation. ELISA was conducted to assess vitamin B12, glutathione, and cytokines changes. UHPLC-MRM-MS/MS was used to detect changes in the intermediates of the one-carbon cycle. Flow cytometry is used to detect cell cycle, ROS, mitoROS, and CD14 changes.
RESULTS
Elevated TCN2 in monocytes was correlated positively with disease progression and specific tissue injuries. Using CD14+ monocytes and TCN2 genetically modified THP1 cell lines, we found that the TCN2 was induced by LPS in serum from SLE patients. TCN2 heterozygous knockout inhibited cellular vitamin B12 uptake and one-carbon metabolism, leading to cell proliferation arrest and decreased Toll-like receptor 4 (TLR4)-mediated CCL2 release. Methionine cycle metabolites, s-adenosylmethionine and homocysteine, rescued these effects, whereas folate treatment proved to be ineffective. Folate deficiency also failed to replicate the impact of TCN2 downregulation on THP1 inflammatory response.
CONCLUSION
Our study elucidated the unique involvement of TCN2-driven one-carbon flux on SLE-associated monocyte behavior. Increased TCN2 may promote disease progression and tissue damage by enhancing one-carbon flux, fostering monocyte proliferation, and exacerbating TLR4 mediated inflammatory responses. The inhibition of TCN2 may be a promising therapeutic approach to ameliorate SLE.
Topics: Humans; Toll-Like Receptor 4; Lupus Erythematosus, Systemic; Monocytes; Transcobalamins; Cell Proliferation; Female; Folic Acid; Male; Adult; Inflammation; Middle Aged; THP-1 Cells; Carbon; Vitamin B 12; Case-Control Studies
PubMed: 38881906
DOI: 10.3389/fimmu.2024.1339680 -
Journal of the European Academy of... Jul 2024Skin aging has long been considered a purely cosmetic problem. However, as life expectancy increases, skin aging is taking on a functional dimension that goes beyond... (Review)
Review
Skin aging has long been considered a purely cosmetic problem. However, as life expectancy increases, skin aging is taking on a functional dimension that goes beyond cosmetics and appearance. Preventive or therapeutic strategies are needed to target cellular senescence, a key process underlying the alterations in skin function and appearance that occur with aging, as well as to address the age-related skin changes associated with 'dermatoporosis' and chronic skin insufficiency/fragility syndrome. Thus, given the need for effective anti-aging products that improve both the appearance and function of the skin, it is essential to distinguish active ingredients that have been proven to be effective, among the large number of available over-the-counter cosmeceuticals. This brief review focuses on a core group of topical actives, describing their clinical effects on senescence and aging, and their molecular mechanisms of action. These actives include hyaluronic acid, which has hydrating and viscoelastic properties and has been shown to reduce skin atrophy; retinaldehyde, which activates retinoid receptors and increases cutaneous elasticity; vitamins C and E, which provide stable oxidative protection; and niacinamide, which reduces inflammation and mitigates the effects of senescence.
Topics: Skin Aging; Humans; Cellular Senescence; Hyaluronic Acid; Ascorbic Acid; Niacinamide; Vitamin E; Cosmeceuticals; Skin
PubMed: 38881445
DOI: 10.1111/jdv.19648 -
The Journal of the Association of... May 2024Diabetes mellitus (DM) is a common metabolic disorder that has been defined by hyperglycemia. Diabetic patients usually have high levels of oxidative stress....
INTRODUCTION
Diabetes mellitus (DM) is a common metabolic disorder that has been defined by hyperglycemia. Diabetic patients usually have high levels of oxidative stress. Mitochondrial dysfunction and inflammation of blood vessels are associated with a greater need for micronutrients in diabetic patients. These micronutrients may have an association with the complications in diabetics. The purpose of this study was to show the association of diabetic peripheral neuropathy (DPN) with levels of micronutrients such as copper (Cu), zinc (Zn), magnesium (Mg), and vitamin B (Vit B).
MATERIALS AND METHODS
This cross-sectional study was conducted in the Department of Medicine, Lala Lajpat Rai Memorial Medical College, Meerut. A total of 130 randomly selected cases of confirmed type-2 diabetic patients were included in this study. DPN cases were identified using the Michigan neuropathy screening instrument. Out of 130 diabetic patients, 28 patients were found to have diabetic neuropathy. The level of various micronutrients was assessed and correlated with the development of DPN.
RESULTS
The association of DPN with Zn (p-value of 0.02) and Vit B12 (p-value of 0.008) was found to be significant, whereas Cu (p-value of 0.57) and Mg (p-value of 0.24) were found to be insignificant.
Topics: Humans; Diabetic Neuropathies; Cross-Sectional Studies; Micronutrients; Middle Aged; Male; Female; Zinc; Copper; Diabetes Mellitus, Type 2; Magnesium; Vitamin B 12; Aged; Adult
PubMed: 38881112
DOI: 10.59556/japi.72.0493 -
Gan To Kagaku Ryoho. Cancer &... May 2024A 74-year-old man underwent laparoscopic-assisted high anterior resection with D3 lymph node dissection for rectal cancer, which was simultaneously accompanied by...
A 74-year-old man underwent laparoscopic-assisted high anterior resection with D3 lymph node dissection for rectal cancer, which was simultaneously accompanied by multiple liver metastases. The patient received mFOLFOX6 therapy for liver metastases 1 month after the surgery. Anorexia, nausea, and vomiting appeared on the second day of treatment. On the third day of treatment, impaired consciousness(JCS Ⅱ-20)and flapping tremors appeared. Blood tests revealed hyperammonemia, and the patient was diagnosed with impaired consciousness due to hyperammonemia, which was inferred to be caused by 5-fluorouracil(5-FU). Intravenous infusion and branched-chain amino acids were administered, and the patient recovered. The underlying disease of renal dysfunction, constipation, and dehydration due to chemotherapy might have induced the hyperammonemia. It is important to note that hyperammonemia can lead to a disturbance of consciousness during chemotherapy including 5-FU.
Topics: Humans; Hyperammonemia; Male; Fluorouracil; Aged; Rectal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Leucovorin; Organoplatinum Compounds; Liver Neoplasms; Consciousness Disorders
PubMed: 38881070
DOI: No ID Found -
Gan To Kagaku Ryoho. Cancer &... May 2024A 73-year-old woman underwent a descending colectomy for descending colon cancer. The tumor was graded as pStage Ⅲb(pT3[SS], pN1b, pM0, Cur A), according to the 9th...
A 73-year-old woman underwent a descending colectomy for descending colon cancer. The tumor was graded as pStage Ⅲb(pT3[SS], pN1b, pM0, Cur A), according to the 9th edition of the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma. Postoperative treatment of adjuvant chemotherapy comprised oral tegafur/uracil and Leucovorin for 6 months with no evident recurrence. However, contrast-enhanced CT and FDG-PET/CT examination 8 years and 7 months after surgery revealed a 30 mm irregular recurrent tumor in the left iliac fossa. Since the tumor was adjacent to the left psoas muscle, it was considered that RM0(no tumor identified at the radial margin)could not be achieved in that region. Owing to the patient's good general condition, systemic chemotherapy with CAPOX+bevacizumab was administered. Although adverse events prompted discontinuation of the treatment during the first course, the recurrent tumor had significantly regressed. Systemic chemotherapy with mFOLFOX6+bevacizumab as selected subsequent treatment achieved a significant tumor shrinkage to date. Although a recurrence more than 5 years after curative resection of colorectal cancer is extremely rare, the possibility of late recurrence must be considered in patients with well-differentiated tumors who received adjuvant chemotherapy and had negative vascular invasion.
Topics: Humans; Aged; Female; Colonic Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Recurrence; Colectomy; Time Factors; Colon, Descending; Bevacizumab; Treatment Outcome; Leucovorin
PubMed: 38881069
DOI: No ID Found -
Gan To Kagaku Ryoho. Cancer &... May 2024Metastatic colorectal cancer with KRAS wild type is treated using a range of drug regimens, including fluorouracil, irinotecan, and Leucovorin(FOLFIRI)plus...
OBJECTIVE
Metastatic colorectal cancer with KRAS wild type is treated using a range of drug regimens, including fluorouracil, irinotecan, and Leucovorin(FOLFIRI)plus bevacizumab(Bmab), cetuximab(Cmab), or panitumumab(Pmab). The present study aimed to identify the optimal regimen using a decision analysis method, in combination with clinical and economic evidence.
METHOD
A simple Markov model with a monthly cycle time was constructed. Probabilistic variables for input into the model were derived from randomized controlled trials. Direct costs for the drugs, laboratory analyses, and medical staff were calculated and used in the model.
RESULTS
The expected survival times and costs of FOLFIRI alone and combination therapies were 20.9 months and 2,299,198 yen for FOLFIRI, 29.9 months and 8,929,888 yen for Bmab, 27.8 months and 11,811,849 yen for Cmab, and 22.6 months and 8,795,622 yen for Pmab. The incremental cost-effectiveness ratios to FOLFIRI were 736,743 yen/month for Bmab, 1,378,645 yen/month for Cmab, and 3,821,426 yen/month for Pmab.
CONCLUSIONS
These findings suggested that these regimens were not sufficiently cost-effective, although they have excellent therapeutic efficacy. From the economic point of view, these combination regimens were inferior to FOLFIRI alone.
Topics: Leucovorin; Humans; Antineoplastic Combined Chemotherapy Protocols; Cost-Benefit Analysis; Colorectal Neoplasms; Fluorouracil; Camptothecin; Neoplasm Metastasis; Clinical Decision-Making; Cost-Effectiveness Analysis
PubMed: 38881065
DOI: No ID Found