Gestational age, maternal smoking, neurological lesion and retinopathy predict strabismus at age 5.5 in preterm children.

AIM: Prematurity is a risk factor for strabismus, but the roles of intermediate factors like retinopathy of prematurity (ROP) and neurological lesions are less understood. We aimed to identify neonatal risk factors for strabismus at age 5.5 in preterm children. METHODS: Data were extracted from the étude épidémiologique sur les petits âges gestationnels 2 cohort, a French prospective population-based study of preterm children born in 2011 with gestational age of 34 weeks or less. Strabismus was recorded during a medical interview at 5.5 years. Using a directed acyclic graph, intermediate and confounding factors were identified. Total and direct effects of gestational age on strabismus risk were analysed using generalised estimating equation. RESULTS: Among 2419 children assessed, 274 (52.6% male) presented strabismus at 5.5 years. The direct effect of gestational age remained significant after adjustment (p < 0.001). In the complete imputed model: maternal smoking during pregnancy (odds ratio, OR 1.8; 95% confident interval, 95% CI 1.3-2.6), neonatal severe cerebral lesions (OR 2.9, 95% CI 1.8-4.6) and severe ROP (OR 4.2, 95% CI 1.9-9.0) were independent risk factors. CONCLUSION: Special attention is needed regarding strabismus screening at age 5.5 in preterm children, even without severe cerebral lesions and ROP. Smoking cessation during pregnancy should be encouraged.

Association between endothelial function and skin advanced glycation end-products (AGEs) accumulation in a sample of predominantly young and healthy adults.

BACKGROUND: In populations with chronic disease, skin autofluorescence (SAF), a measure of long-term fluorescent advanced glycation end-products (AGEs) accumulation in body tissues, has been associated with vascular endothelial function, measured using flow-mediated dilation (FMD). The primary aim of this study was to quantify the relationship between endothelial function and tissue accumulation of AGEs in adults from the general population to determine whether SAF could be used as a marker to predict early impairment of the endothelium. METHODS: A cross-sectional study was conducted with 125 participants (median age: 28.5 y, IQR: 24.4-36.0; 54% women). Endothelial function was measured by fasting FMD. Skin AGEs were measured as SAF using an AGE Reader. Participant anthropometry, blood pressure, and blood biomarkers were also measured. Associations were evaluated using multivariable regression analysis and were adjusted for significant covariates. RESULTS: FMD was inversely correlated with SAF (ρ = -0.50, P < 0.001) and chronological age (ρ = -0.51, P < 0.001). In the multivariable analysis, SAF, chronological age, and male sex were independently associated with reduced FMD (B [95% CI]; -2.60 [-4.40, -0.80]; -0.10 [-0.16, -0.03]; 1.40 [0.14, 2.67], respectively), with the multivariable model adjusted R2 = 0.31, P < 0.001. CONCLUSIONS: Higher skin AGE levels, as measured by SAF, were associated with lower FMD values, in a predominantly young, healthy population. Additionally, older age and male participants exhibited significantly lower FMD values, corresponding with compromised endothelial function. These results suggest that SAF, a simple and inexpensive marker, could be used to predict endothelial impairment before the emergence of any structural artery pathophysiology or classic cardiovascular disease risk markers. TRIAL REGISTRATION: The study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000821897) and concurrently entered into the WHO International Clinical Trials Registry Platform under the same ID number.

Recent advances in the potential of Phyllanthus emblica L. and its related foods for combating metabolic diseases through methylglyoxal trapping.

Methylglyoxal (MG) serves as the primary precursor for the nonenzymatic glycation of proteins and DNA, leading to advanced glycation end products (AGEs). Regular intake of dietary MG is strongly correlated with low-grade inflammation, potentially accelerating the pathogenesis of metabolic diseases, including obesity, diabetes, cancers, liver diseases, Alzheimer's disease, cardiovascular diseases, aging, and bone loss. Although pharmaceutical agents (pimagedine and candesartan) have been developed to inhibit MG formation, they often come with serious side effects (nausea, diarrhea, headache, gastrointestinal disturbance, symptomatic hypotension, abnormal renal and liver function tests, development of antinuclear antibody, pernicious-like anemia, and hyperkalemia), highlighting the need for an efficient and safe approach to scavenging MG. Phyllanthus emblica Linn fruit, a nutritious edible fruit, and medicinal plant contains over 300 bioactive compounds. Among twenty-three herbals, 100 µg/mL of the aqueous extract of Phyllanthus emblica fruit (APF) exhibits the highest potency in trapping MG, achieving an 87.3 % reduction under d-fructose induced BSA-AGEs formation. However, there are few reports detailing APF and its related foods' specific impact on disease prevention through MG trapping. This review summarizes the mechanisms through which MG is linked to the development of metabolic diseases and provides several strategies for reducing MG levels using APF and its bioactive compounds. The potential antiglycation properties of APF may offer new applications in the food industry and pharmacological research.

Huang-Lian-Jie-Du Decoction Alleviates Diabetic Encephalopathy by Regulating Inflammation and Pyroptosis via Suppression of AGEs/RAGE/NF-κB Pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Cognitive dysfunction associated with diabetes, known as diabetic encephalopathy (DE), is a grave neurodegenerative condition triggered by diabetes, and persistent inflammation plays a vital role in its development. The renowned traditional Chinese medicine Huang-Lian-Jie-Du Decoction (HLJDD) is clinically proven to manage diabetes mellitus and Alzheimer's disease and is famous for its heat-clearing and detoxifying effects. However, the underlying mechanisms through which HLJDD affects DE remain to be elucidated. AIM OF THE STUDY: To explore the beneficial effects of HLJDD on improving cognitive dysfunction in DE mice. STUDY DESIGN AND METHODS: A diabetic mouse was established through a high-fat diet and subsequent administration of streptozotocin over five consecutive days. After the animals were confirmed to have diabetes, they were treated with HLJDD. After oral administration of HLJDD or metformin for 14 weeks, behavioral tests were used to assess their cognitive capacity. Biochemical analyses were then performed to detect levels of glucose metabolism, followed by histological analyses to assess pathological damage. Furthermore, AGEs/RAGE/NF-κB axis related proteins were detected by Western blot or immunofluorescence techniques. An advanced UPLC-Q-Orbitrap HRMS/MS analytical technique utilizing a chemical derivatization strategy was employed for comprehensive metabolic profiling of carbonyl compounds in the plasma of DE mice. RESULTS: Pharmacological assessment revealed that HLJDD effectively mitigated cognitive dysfunction, normalized glucose metabolic imbalances, and repaired neuronal damage in DE mice. It reduced neuroinflammation by attenuating carbonyl stress, deactivating astrocytes and microglia, and preserving dopaminergic neurons. Additionally, metabolomics analysis revealed 18 carbonyl compounds with marked disparities between DE and control mice, with 12 metabolites approaching normal levels post-HLJDD intervention. Further investigations showed that HLJDD regulated inflammation and pyroptosis through suppressing AGEs/RAGE/NF-κB pathways. CONCLUSION: Our study indicated that HLJDD could ameliorate carbonyl stress via the regulation of carbonyl compound metabolism profiling, and inhibiting the AGEs/RAGE/NF-κB pathway, thereby alleviating inflammation and pyroptosis to exert beneficial effects on DE.

Diagnostic accuracy of Ages and Stages Questionnaire, Third Edition to identify abnormal or delayed gross motor development in high-risk infants.

AIM: To investigate the diagnostic accuracy of parent-completed Ages and Stages Questionnaire, Third Edition (ASQ-3) to identify abnormal or delayed gross motor development in infants born less than 1000 g or less than 28 weeks gestation. METHODS: Prospective cohort study of high-risk infants comparing ASQ-3 as the index test with concurrent score on Alberta Infant Motor Scale (AIMS) as the reference standard, at 4-, 8- and 12-month corrected (post-term) age. Reference standard positivity cut-offs were 'Abnormal motor development' (AIMS Clinical Range) and 'Motor delay' (AIMS score >1 SD below mean, not captured in Clinical Range). RESULTS: Participating infants (n = 191) had mean gestational age (95% confidence interval (CI)) 26.8 weeks (26.6-27.1) and mean birthweight (95% CI) 870 g (844-896). AIMS rated 51%, 31% and 23% of infants as having 'Abnormal motor development' and 12%, 28% and 13% with 'Motor delay', at 4, 8 and 12 months, respectively. Diagnostic accuracy of ASQ-3 to identify abnormal motor development was acceptable for older infants only if 'Monitor' cut-off was used: sensitivity (95% CI) 33% (23-44), 86% (73-95) and 80% (63-92) and specificity (95% CI) 84% (74-92), 76% (66-84), and 76% (67-83) at 4, 8 and 12 months, respectively. ASQ-3 sensitivity to identify motor delay was low. CONCLUSIONS: ASQ-3 has poor sensitivity to identify abnormal or delayed motor development at 4 months. Using the 'Monitor' cut-off improves the diagnostic accuracy of ASQ-3 for identification of older infants with abnormal motor development who are at high risk of motor disability. However, ASQ-3 has poor sensitivity to identify motor delay. Clinical motor assessment of high-risk infants is recommended, particularly in early infancy.

Evaluating potential of H'mong chicken bone marrow-derived mesenchymal stem cells at different ages for primordial germ cells' feeder layer.

Primordial germ cells (PGCs) have potential applications in genetic conservation, vaccination, tissue repair therapies, and genetic research. Chicken bone marrow-derived mesenchymal stem cells (cbMSCs) is a good candidate for co-culture with PGCs. However, there is no consensus on the optimal age of donors. In this study, we aimed to compare specific parameters of H'Mong cbMSCs obtained from day 14th and 19th embryos, and day 3rd newborns. Isolated cbMSCs showed characteristics of MSCs. Cells had fibroblast-like morphology, plastic-adherent, expressed specific markers of MSCs and multilineage differentiation potential. The growth rate of cells from day 19th embryos was higher than from other ages. Moreover, cells expressed markers of pluripotency such as Nanog, PouV, Sox2, CVH, DAZL, and KIT, known for their role in maintaining stem cell self-renewal and pluripotency. As feeder cells, cbMSCs from three different ages promoted proliferation of H'Mong PGCs during co-culture. These results suggested that cbMSCs from different ages can be used for co-culture H'Mong PGCs which were further used for genetic preservation of H'Mong chicken or gene editing research.

Comprehensive research on the properties of advanced glycation end products in food and biological samples and their harmful role in inducing metabolic diseases.

Advanced glycation end products (AGEs) are formed by the Maillard reaction, a nonenzymatic process that occurs widely in cooking, food processing, and within the human body. Primarily, AGEs are formed by the glycation of reducing sugars with amino groups, and this process is heat-dependent. With changes in lifestyle, there has been an increase in the diversity of dietary habits, including those patterns associated with Western diets, which include the consumption of processed foods that are rich in AGEs. Excessive intake and exposure to AGEs are known to cause abnormalities in body function such as obesity, diabetes, and fatty liver, and the beneficial effects of AGEs in food processing in improving food flavor and quality. To obtain meaningful data regarding AGEs in a variety of food and human samples, it is necessary to more precisely characterize and analyze the AGEs extracted from samples to obtain accurate results. This review explores the recent analytical research and characterization of AGEs in foods, including casein, ß-lactoglobulin, soy protein, and meat protein, and in human samples, such as glycated-albumin, hemoglobin, and plasma. Additionally, it explores the metabolic fate of AGEs in the body and the mechanisms of disease associated with metabolic abnormalities that may be caused by the consumption of foods containing AGEs. This review aims to provide an overview of the perspectives of relevant recent and future research on metabolic abnormalities caused by foods containing AGEs or by AGEs produced in the body.

Abu Bakr Muhammad Ibn Zakariya Al-Razi (Rhazes) (865-925): The Founder of the First Psychiatric Ward.

Abu Bakr Muhammad Ibn Zakariya Al-Razi, also known as Rhazes, was a 10th-century Persian polymath who made significant contributions to medicine, philosophy, chemistry, and psychiatry. He is credited with founding the first psychiatric ward in Baghdad, highlighting the medical treatment of mental illnesses. His empirical and innovative approaches to clinical observation and experimentation laid the basis for modern evidence-based medicine. Al-Razi's comprehensive works, such as "The Comprehensive Book," profoundly influenced both Islamic and European medical practices, securing his legacy as a pivotal figure in medical history. Therefore, the primary objective of this narrative review is to revisit the remarkable contributions of Al-Razi in the field of psychiatry, specifically highlighting his role as the founder of the first psychiatric ward.

[Life expectancy for the regions of the Northwestern Federal District. Part 2: Dynamics of old age threshold.]

The paper continues the study of the population ageing in the regions of the Northwestern Federal District. It characterized population ageing based on prospective ageing indicators that take into account remaining life expectancy. The dynamics of life expectancy (LE) at birth was analyzed. A computation and comparative analysis of the old age threshold for the regions that are part of the Northwestern Federal District have been carried out. A comparative analysis of ageing indicators - traditional and prospective (the proportion of the elderly and the share of the population above the old age threshold) was carried out. It has been found that there are no fundamental differences in the dynamics of life expectancy in older ages, as well as in the of old age threshold, between the regions considered. It is shown that for the male population in almost all regions in 2021, the value of the old age threshold is below 60 years, while for the female population the opposite inequality is observed. Thus, in 2021, the share of men over the old age threshold exceeds the proportion of the elderly in almost all regions considered, and for the female population, the share of the elderly is expected to be higher than the values of the prospective indicator.

Evaluation of the potential of Yushina alpina bamboo fibers from Cameroon for the manufacture of biocomposites.

The Cameroon has two bamboo species indigenous to Africa (the alpine bamboo, Yushina alpina and the savannah bamboo, Oxytenanthera abyssinica), and one largely exotic species, Bambusa vulgaris. However, little on their physical characteristics and strength for the composites materials applications is known for these two indigenous bamboos species in Cameroon. Therefore, in this study, emphasis was laid on the alpine bamboo Y. alpina, to evaluate its potential for biocomposites applications. Y. alpina with ages ranging from 1 to 3 years, 4-5 years, and 7 years were characterized. The mechanical and physical properties of these three age ranges were compared. In the first place, the surface texture of the fibers was examined by scanning electron microscopy. Afterwards, chemical treatment was performed on the fibers with 1 % NaOH. In addition, the chemical bonds of the molecules (functional groups) were identified by Fourier transform infrared spectra (FTIR) and the thermal properties of the fibers were examined with a thermogravimetric analyzer. Furthermore, the fibers density was assessed using the Rilem protocol and a tensile testing machine was used to determine the mechanical properties of the treated fibers with 1 % of NaOH. Finally, a dynamic mechanical analysis of 7-year-old Y. alpina fibers was carry out. The results indicate that the Young's modulus of treated fibers with ages ranging from 1 to 3 years, 4-5 years, and 7 years were around 18 GPa, 10 GPa, and 14 GPa, respectively. In summary, this study underlines two primary points: (1) providing a platform for researchers to better understand the influence of age on the physical and mechanical properties of indigenous bamboo Y. alpina; and (2) providing a platform to validate suitable designs of biocomposites materials with Y. alpina.

Rhizosphere effects and microbial N limitations drive the root N limitations in the rhizosphere during secondary succession in a Pinus tabuliformis forest in North China.

Introduction: Rhizosphere effects (REs) have recently been identified as important regulators of root and microbial nutrient acquisition and are positively involved in nutrient cycling of belowground carbon (C), nitrogen (N), and phosphorus (P). Nutrient conditions of the fine roots and soil N are likely to influence REs. Still, it is unclear how REs of soil nutrients themselves variably impact the supply of nutrients to plants in terms of the responses to soil N due to succession. Methods: In this study, we applied both fine roots and extracellular enzymes for vector analysis and stoichiometry of N:P to explore the metabolic limitations of roots and rhizospheric soil microbes and their relationships with REs across five levels of soil N (0, 5, 10, 15, and 20 kg N m-2 year-1) along successional age classes of 42, 55, and 65 years in a Pinus tabuliformis forest. Results: Overall, the metabolism of root and rhizospheric soil microbes was mediated by soil N. N limitation of roots initially decreased before increasing, whereas that of microbes demonstrated opposite trends to the N levels owing to competition for inorganic N between them by REs of NO3 --N. However, N limitations of both roots and microbes were alleviated in young stands and increased with succession after the application of N. In addition, root N limitations were manipulated by REs of three different soil N-related indicators, i.e., total N, NH4 +-N, and NO3 --N. Rhizospheric soil microbial N limitation was almost unaffected by REs due to their strong homeostasis but was an important driver in the regulation of root N limitation. Discussion: Our results indicated that successional age was the most critical driver that directly and indirectly affected root N metabolism. However, the level of N application had a slight effect on root N limitation. Microbial N limitation and variations in the REs of N indicators regulated root N limitation in the rhizosphere. As a result, roots utilized REs to sequester N to alleviate N limitations. These findings contribute to novel mechanistic perspectives on the sustainability of N nutrition by regulating N cycling in a system of plant-soil-microbes in the rhizosphere to adapt to global N deposition or the heterogeneous distribution of bioavailable soil N with succession.

Advanced glycation end products mediate biomineralization disorder in diabetic bone disease.

Patients with diabetes often experience fragile fractures despite normal or higher bone mineral density (BMD), a phenomenon termed the diabetic bone paradox (DBP). The pathogenesis and therapeutics opinions for diabetic bone disease (DBD) are not fully explored. In this study, we utilize two preclinical diabetic models, the leptin receptor-deficient db/db mice (DB) mouse model and the streptozotocin-induced diabetes (STZ) mouse model. These models demonstrate higher BMD and lower mechanical strength, mirroring clinical observations in diabetic patients. Advanced glycation end products (AGEs) accumulate in diabetic bones, causing higher non-enzymatic crosslinking within collagen fibrils. This inhibits intrafibrillar mineralization and leads to disordered mineral deposition on collagen fibrils, ultimately reducing bone strength. Guanidines, inhibiting AGE formation, significantly improve the microstructure and biomechanical strength of diabetic bone and enhance bone fracture healing. Therefore, targeting AGEs may offer a strategy to regulate bone mineralization and microstructure, potentially preventing the onset of DBD.

Advanced Glycation End-Products Acting as Immunomodulators for Chronic Inflammation, Inflammaging and Carcinogenesis in Patients with Diabetes and Immune-Related Diseases.

Increased production of advanced glycation end products (AGEs) among reducing sugars (glucose, fructose, galactose, or ribose) and amino acids/proteins via non-enzymatic Maillard reaction can be found in lifestyle-related disease (LSRD), metabolic syndrome (MetS), and obesity and immune-related diseases. Increased serum levels of AGEs may induce aging, diabetic complications, cardiovascular diseases (CVD), neurodegenerative diseases (NDD), cancer, and inflamm-aging (inflammation with immunosenescence). The Maillard reaction can also occur among reducing sugars and lipoproteins or DNAs to alter their structure and induce immunogenicity/genotoxicity for carcinogenesis. AGEs, as danger-associated molecular pattern molecules (DAMPs), operate via binding to receptor for AGE (RAGE) or other scavenger receptors on cell surface to activate PI3K-Akt-, P38-MAPK-, ERK1/2-JNK-, and MyD88-induced NF-κB signaling pathways to mediate various pathological effects. Recently, the concept of "inflamm-aging" became more defined, and we have unveiled some interesting findings in relation to it. The purpose of the present review is to dissect the potential molecular basis of inflamm-aging in patients with diabetes and immune-mediated diseases caused by different AGEs.

Exploring Cognitive Impairments Associated with Primary Open-Angle Glaucoma and Exfoliation Glaucoma.

This study explored the link between different types of glaucoma and cognitive function in a cohort of 620 Japanese patients. Participants were categorized into primary open-angle glaucoma (PG), exfoliation glaucoma (EG), and non-glaucomatous control groups. The findings revealed a significant decline in cognitive function as indicated by the Mini-Cog test in the EG group (mean ± SD: 4.0 ± 1, 95% CI: 3.9 to 4.2) compared to the PG group (4.4 ± 0.1, 4.3 to 4.5, p < 0.0001). Levels of fingertip measured advanced glycation end-products (AGEs) were significantly higher in the EG group (mean ± SD: 0.45 ± 0.006, 95% CI: 0.44 to 0.46) compared to the PG group (0.43 ± 0.004, 0.42 to 0.44, p = 0.0014). Although the multivariate analysis initially showed no direct association between glaucoma types and Mini-Cog scores, the EG group exhibited higher age and intraocular pressure (IOP) compared to the PG group. Further analysis revealed that high levels of AGEs were associated with cognitive decline and decreased mean visual fields in the EG group. Age was identified as a cofounding factor in these associations. An inverse correlation was observed between the accumulation of AGEs and skin carotenoid levels. Early detection of cognitive decline in glaucoma patients could enable timely intervention to preserve visual fields. Fingertip measurements of skin carotenoids and AGEs offer promising potential as non-invasive, straightforward diagnostic tools that could be widely adopted for monitoring ophthalmic and cognitive health in glaucoma patients.

Advancing the Diagnosis of Diabetic Neuropathies: Electrodiagnostic and Skin Autofluorescence Methods.

INTRODUCTION: Diabetic neuropathy (DN) is a generic term for various neuropathies coexisting in a single patient. Clinical diagnosis alone can be misleading, yet routine electrodiagnostic studies in diabetes care are rare. Skin autofluorescence (SAF) is a recognized DN risk factor with potential screening value. This article highlights the diagnostic challenges and raises awareness of the often underdiagnosed neuropathic conditions in diabetes patients. MATERIAL AND METHODS: We present common entrapment neuropathy cases from our diabetes clinic's electrodiagnosis laboratory in Iași, Romania. We selected seven type 2 diabetes patients with sensory or sensory-motor distal polyneuropathy and atypical DN presentations investigated through electroneurography (ENG) and electromyography (EMG) with the Neurosoft® EMG instrument and SAF measured by standard procedures. Subsequently, a narrative literature review was conducted. RESULTS: Entrapment neuropathies were diagnosed in all the patients: three carpal tunnel syndromes, two ulnar neuropathies (one proximal, one distal), one peroneal neuropathy, and one case of meralgia paresthetica. The lower-limb cases showed radiculoplexopathy, and there was one case of superficial radial nerve neuropathy. The SAF values ranged from 2.5 AU to 3.4 AU. CONCLUSIONS: Electrodiagnosis is essential for detecting focal neuropathies in patients with sensory-motor distal polyneuropathy. Elevated SAF levels may correlate with symptom severity, although further research, including large cohorts, is needed.

A One-Month Advanced Glycation End Products-Restricted Diet Improves CML, RAGE, Metabolic and Inflammatory Profile in Patients with End-Stage Renal Disease Undergoing Haemodialysis.

Exogenous and endogenous advanced glycation end products (AGEs) contribute to the pathogenesis and progression of renal disease. This is a one-month controlled dietary counseling trial that restricts nutritional AGEs in patients with end-stage renal disease (ESRD) undergoing haemodialysis (n = 22 participants in the intervention and n = 20 participants in the control group). Haematological, biochemical markers, the soluble form of the receptor for AGEs (sRAGE), and carboxymethyl lysine (CML) were measured at baseline and at follow-up. Mononuclear cells were isolated and the protein expression of RAGE and the inflammatory marker COX-2 was measured using Western immunoblotting. The intervention group presented a lower increase in CML compared to the control group (12.39% median change in the intervention vs. 69.34% in the control group, p = 0.013), while RAGE (% mean change -56.54 in the intervention vs. 46.51 in the control group, p < 0.001) and COX-2 (% mean change -37.76 in the intervention vs. 0.27 in the control group, p < 0.001) were reduced compared to the control group. sRAGE was reduced in both groups. In addition, HbA1c (at two months), total cholesterol, and triglycerides were reduced in the intervention versus the control group. The adoption of healthy cooking methods deserves further research as a possible way of modulating inflammatory markers in patients with CKD.

Candidatus Midichloria mitochondrii can be vertically transmitted in Hyalomma anatolicum.

In this study, a tick intracellular symbiont, Candidatus Midichloria mitochondrii, was detected in Hyalomma anatolicum from Xinjiang, China. Morphological identification and cytochrome oxidase subunit I sequence alignment were used for molecular identification of the tick species. PCR detection further revealed the presence of endosymbiont C. M. mitochondrii in the tick. Specific primers were designed for Groel and 16S rRNA genes of C. M. mitochondrii for PCR amplification and phylogenetic analysis. To further investigate the vertical transmission characteristics of C. M. mitochondrii, specific primers were designed based on the FabⅠ gene fragment to detect C. M. mitochondrii in different developmental stages and organs of the tick using qPCR. Of the 336 tick specimens collected from the field, 266 samples were identified as H. anatolicum on the basis of morphological characteristics. The gene fragment alignment results of COI confirmed that these ticks were H. anatolicum. The phylogenetic analysis showed that Groel gene of C. M. mitochondrii clustered with Midichloria strains detected in Ixodes ricinus ticks from Italy and Ixodes holocyclus ticks from Australia, with 100% sequence similarity. Furthermore, the 16S rRNA gene of C. M. mitochondrii clusters with the strains isolated from Hyalomma rufipes ticks in Italy, exhibiting the highest degree of homology. qPCR results showed that C. M. mitochondrii was present at all developmental stages of H. anatolicum, with the highest relative abundance in eggs, and lower relative abundance in nymphs and unfed males. With female tick blood feeding, the relative abundance of C. M. mitochondrii increased, and a particularly high relative abundance was detected in the ovaries of engorged female ticks. This study provides information for studying the survival adaptability of H. anatolicum, and provides data for further investigation of the mechanisms regulating tick endosymbionts in ticks, enriching the reference materials for comprehensive prevention and control of tick-borne diseases.

Impact of sex, age at onset, and anti-cN1A antibodies on sporadic inclusion body myositis.

BACKGROUND: Inclusion body myositis (IBM) is a progressive myopathy occurring in patients over 45 years of age, with heterogeneous and variable clinical features. This study aimed to determine the influence of autoantibodies, gender, and age of onset on the clinical features of IBM. METHODS: Medical records and muscle histology findings of 570 participants with suspected IBM were reviewed. Various characteristics of patients who met the 2011 ENMC IBM diagnostic criteria were compared based on the presence of anti-cytosolic 5'-nucleotidase 1 A (cN1A) autoantibodies, gender, age of onset, and disease duration. RESULTS: Of the 353 patients who met the criteria, 41.6% were female. The mean age at onset was 64.6 ± 9.3 years, and the mean duration from onset to diagnosis was 5.7 ± 4.7 years. 196 of the 353 patients (55.5%) were positive for anti-cN1A autoantibodies and 157 were negative. Logistic regression showed that patients with anti-cN1A autoantibodies had a higher frequency of finger flexion weakness. Multiple regression showed that patients with later age of onset had shorter disease duration, lower BMI, and lower serum CK levels. Male patients had a higher frequency of onset with finger weakness and female patients had a lower BMI. CONCLUSION: Autoantibodies, gender, age of onset, and disease duration may influence the clinical presentation of IBM, highlighting the need for a precision medicine approach that considers these factors along with the underlying mechanisms of the disease.

Advanced glycation end products promote the progression of endometrial cancer via activating the RAGE/CHKA/PI3K/AKT signaling pathway.

Endometrial cancer (EC) is a common malignant tumor that is closely associated with metabolic disorders such as diabetes and obesity. Advanced glycation end products (AGEs) are complex polymers formed by the reaction of reducing sugars with the amino groups of biomacromolecules, mediating the occurrence and development of many chronic metabolic diseases. Recent research has demonstrated that the accumulation of AGEs can affect the tumor microenvironment, metabolism, and signaling pathways, thereby affecting the malignant progression of tumors. However, the mechanism by which AGEs affect EC is unclear. Our research aimed to investigate how AGEs promote the development of EC through metabolic pathways and to explore their potential underlying mechanisms. Our experimental results demonstrated that AGEs upregulated the choline metabolism mediated by choline kinase alpha (CHKA) through the receptor for advanced glycation end products (RAGE), activating the PI3K/AKT pathway and enhancing the malignant biological behavior of EC cells. Virtual screening and molecular dynamics simulation revealed that timosaponin A3 (timo A3) could target CHKA to inhibit AGE-induced progression of EC and that a newly discovered CHKA inhibitor could be a novel targeted inhibitor for the treatment of EC. This study provides new therapeutic strategies and contributes to the treatment of EC.