Effect of applying selenium fertilizer to improve soil and increase selenium level in food for prevention and treatment of Kaschin-Beck disease

For prevention and treatment of Kaschin-Beck disease by applying Se fertilizer to soil to increase Se up to normal level for the wheat grains is introduced in this paper. After use this measure the intake of Se by the residents in the exemplary area increased from 10.4μg to 33.6 μg per day in average. After supplementing Se to human body one year, there is no new patient found among 300 healthy children in the exemplary area but 4 patients found among 264 healthy children in the control area. It is shown that by applying Se fertilizer to KBD area is a effective way for preventing and cure this disease.

Study on correlation between humic acid and selenium in Kaschin-Beck disease areas

The relationship between humic acid and selenium content was studied in this research. The results of calculation showed that there is more humic acid and less selenium in Kaschin-Beck disease areas in China. Fulvic acid in soil could increase selenium level in plants. The chemical bonding between humic acid and selenium was observed with an I.R. spectroscope. It was remarkable for the changes of absorption peak and frequency in 1100-1000 cm-1, 900-700 cm-1.

The roles of organic degradation products andselenium in the pathogenesis ofKaschin-Beck disease

An investigation on the organic degradation products and selenium in the pathogenesis of Kaschin-Beck disease was carried out. The results demonstrated that the organic degradation products existed in food and drinking water were the pathogens of the KBD; their leading pathological process of cells would be 'membrane injury' due to peroxide. As GSH-Px is a selenium contained enzyme, therefore insufficient selenium would be one of the most important conditions to cause KBD.

Study on the action and mechanism of humic acids in Kaschin-Beck disease

Humic acids, especially FA in fractions, contain more oxygen functional groups. In this experiment, on the basis of confirming the action of humic acids on KBD, what was studied is the biological effects of one of main oxygen functional groups, hydroxy group (-OH). The results indicate that inducing pathologic process of KBD, obviously decrease the GSH-Px activity and induce peroxidation membrane injury of tissue. The SOD activity increase in the tissues caused by oxygen functional groups showed that enhancing of free radical reaction should not be neglected.

Redox potential E_H [Se(VI)/Se(IV)] of aqueous extractof soils from Yongshou Kaschin-Beck diseaseregion and the influence by humic acid

The relation between EH [Se(VI)/Se(IV)] and pH of soil aqueous extract in Kaschin-Beck disease region and the effects of natural redox agents, namely humic substances, MnO2 and Fe2+, on the redox property of the system were studied. The results indicated that both humic acid and Fe2+ could enhance the reducibility of Se(VI) and MnO2, a limited oxidizability for Se(IV). Fe2+ showed a weak reducibility only at low pH value. The reducibilities of three sulfur-containing compounds for Se(VI) were in following order:thioglycollic acid > L-cysteine > sulfide

Research on organic matters in the drinking water of Kaschin-Beck disease area

Organic matters in drinking water of Kaschin-Beck disease areas were extracted. Then analyses and characterization were performed by means of multiply chemical and physical methods. The results did not show the obvious difference in the frame structure of humic substances and the structure of rmcromolecular compounds in the drinking water of disease and non-disease areas, but the difference in the contents of some micromolecular compounds and radicals. The investigation also includes the preliminary research on the photoreaction of drinking water from disease and non-disease areas and the accumulation of natural organic matter in the bone of tested animals.

The epidemic characteristics of Kaschin-Beck disease (KBD) in different eco-environments

Epidemiological survey of 573 families, clinical examination of 2593 persons, and X-ray examination of 1136 persons (in 16 typical endemic villages) were conducted, based on the classification of endemiology for KBD disease areas, i.e, mountain type, loess plateau type, plateau type, and flatlands type. It was revealed that the KBD disease areas exhibited the regular pattern of corming-into-being, development and passing-away and the characteristics of growth and decline. Further, it was found clinically that the disease areas may be divided into 4 types, i.e., recent onset, developing, stable, and historical. This division is simple and easy, practical, scientific, and reliable and can be applied by medical personnel at different levels.

Role of interaction between selenium and organic matters on causes of Kaschin-Beck disease

Influences of organic matters of soil and water on speciation and biological utilization of selenium are discussed. Humic acid is found to be the main pool of selenium in soil and affects the bio-availability of the element in soil-plant system. Fulvic acid from drinking water inhibits the absorption of selenium taken from diet. The relationship between high content of organic matters of water and selenium deficiency on the causes of KBD could be reflected in the limited synthesis of glutathione peroxidase, which is generally stimulated by fulvic acid from drinking water.

A retrospective survey on the effect of Kaschin-Beck disease prophylaxis by a change of water sources

In order to provide further references for studing on the causes of Kaschin-Beck discase (KBD) and measuring for its prevention and treatment from a macroscopic view, we analyzed the natural growth and declineof KBD and the effects of selenium and humic acid on its occurrence from an epidemiologic angle. In this article through a retrospective survey on the spots of disease areas by comparison between a change in water sources and that without. It was proved that a change in water sources was an effective measure for the prevention of KBD occurrence, and the pathogenic factor of KBD was one (or several kinds) of organic compounds or active radicals related to water.

Humic acid and free radical in environment of Kaschin-Beck disease areas

The humic acid contents in drinking water and soil in Kaschin-Beck disease areas were found more than that of non-disease areas in this research. Changes of free radical concentration in drinking water were agreed with that of humic acid contents in drinking water of Kaschin-Beck disease areas. A positive correlation of free radical concentration and humic acid content in drinking water has been shown (r=0.913) . The structure of I. R. spectra of humic acid under ultraviolet light has been changed. Thus it indicated that free radical was resulted from benzoqiunonyl groups of humic acid in environment.

Perturbations in Amino Acid Metabolism in Children with Kaschin-Beck Disease: A Study of Urinary Target Metabolomics

Kaschin-Beck disease (KBD) is an endemic and chronic osteoarthropathy characterized by pathological aspects including chondrocyte degeneration, necrosis, progressive loss of articular cartilage, and secondary degenerative osteoarthrosis of epiphyseal cartilage, epiphyseal plate cartilage, and articular cartilage, during puberty[1]. The main clinical symptoms are limb joint pain, thickening, deformation, limited movement, muscle atrophy, and in case of more severely affected patients, short fingers (toes), short limbs, and even short stature[1].

A new hypothesis for the etiology of Kaschin-Beck disease

Kaschin-Beck disease (KBD) could be exogeneous free radical induced endemic osteoarthropathy under conditions of lacking necessary antioxidant defences.especially selenium-cored defence in Chinese eco-en-vironment. Experimental evidences have been provided for the internal relations among previously suggested pathologic factors, i.e., selenium deficiency, organic matters of drinking waterand mycotoxins from contaminated grains, based on the facts that the former is a preventory factor while the others are exogenous freeradical carriers. ESR spectrum shows that these exogenous free radical carriers have a property of semi-quinone compounds and are toxic in in-vitro cartilage cell culture and animal tests in inducing lipid peroxidation process.

Immunology of Kaschin-Beck Disease:Studies on lymphocyte subsets, humoral immunity and their relationship with selenium

Objective To study the humoral immunity status and distribution pattern of lymphocyte subgroups of peripheral blood mononuclear cell (PBMC) in patients with Kaschin-Beck Disease (KBD), and their relationship with erythrocyte selenium.Methods 23 X-ray diagnosed patients, 22 age- and sex- matched healthy children in KBD affected area (KAA), And 25 in KBD non-affected area (KNAA) were randomly selected. Immunohistochemistry with monoclonal antibodies anti-CD4, anti-CD8, anti-CD20 was conducted to analyze the lymphocyte subsets. Serum IgM, IgA, IgG, Complement C3 and C4 were assayed using rate nephelometry (Array 360 System, USA). The contents of erythrocyte selenium was determined by 2,3-diaminonaphthalene fluorescence assay. Results CD4+ and CD8+ cells percentage in PBMCs and serum IgA were significantly lower in KAA than those in KNAA(P<0.05). CD20+ percentage in KAA displayed a decreasing trend compared to KNAA, although not statistically significantly. No statistical differences were found in CD4/CD8 ratio, serum IgG, IgM, C3 and C4 levels. Erythrocyte selenium level in KAA still showed a pronounced decrease compared to that in KNAA. Correlation analysis showed that erythrocyte selenium contents had a strong association with the CD4 cell percentage (r=0.625,P<0.05), and also a close relationship with serum IgA (r=0.462,P<0.05). In addition, we detected a moderate correlation between the serum IgA and CD4+ percentage (r=0.130, P>0.05).Conclusion Taken together, our results suggested that children in KAA had a comparably low cellular immunity level manifested by the marked depression of CD4 and CD8 cells percentage, and their humoral immunity status was also in a state of moderate immune suppression. Of this immune disorder in KBD patients, selenium deficiency probably played a critical role via affecting the distribution pattern of peripheral blood lymphocyte. Selenium-deficiency and immune impairment maybe both have something to do with the cause-effect chain of KBD.

Microglial response to aging and neuroinflammation in the development of neurodegenerative diseases

Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging;they have a great impact on the aging process and are the main risk factors for neurodegeneration.Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases.This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases,including Alzheimer's disease,Huntington's chorea,and Parkinson's disease.This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states.Therefore,inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.

The role of exosomes in adult neurogenesis:implications for neurodegenerative diseases

Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.

Lactate metabolism in neurodegenerative diseases

Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.

Amyloid-beta and tau protein beyond Alzheimer's disease

The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer's disease pathogenesis and are considered the main pathological hallmarks of this devastating disease.Physiologically,these two proteins are produced and expressed within the normal human body.However,under pathological conditions,abnormal expression,posttranslational modifications,conformational changes,and truncation can make these proteins prone to aggregation,triggering specific disease-related cascades.Recent studies have indicated associations between aberrant behavior of amyloid-beta and tau proteins and various neurological diseases,such as Alzheimer's disease,Parkinson's disease,and amyotrophic lateral sclerosis,as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration.Additionally,these proteins have been linked to cardiovascular disease,cancer,traumatic brain injury,and diabetes,which are all leading causes of morbidity and mortality.In this comprehensive review,we provide an overview of the connections between amyloid-beta and tau proteins and a spectrum of disorders.

Unraveling the gut-brain axis:the impact of steroid hormones and nutrition on Parkinson's disease

This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.

Perianal disease in inflammatory bowel disease:Broadening treatment and surveillance strategies for anal cancer

The perianal disease affects up to one-third of individuals with Crohn's disease(CD),causing disabling symptoms and significant impairment in quality of life,particularly for those with perianal fistulising CD(PFCD).The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing.Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents,endoscopic procedures and surgical techniques that show promising results.Among these,mesenchymal stem cells injection is a particularly hopeful therapy.In addition to the burden of fistulas,individuals with perianal CD may face an increased risk of developing anal cancer.This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes.Currently,there is no established formal anal screening programme.In this review,we provide an overview of the current state of the art in managing PFCD,including novel medical,endoscopic and surgical approaches.The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD,intending to propose a risk-based surveillance algorithm.The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.

Muscle strength and non-alcoholic fatty liver disease/metabolicassociated fatty liver disease

This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical applications.NAFLD,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle strength.Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin D.Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD.However,studies investigating the relationship between muscle strength and MAFLD are limited.Owing to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is essential.Furthermore,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.