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[Effects of kidney-tonifying Chinese herbs on thymus regene-ration after rapamycin-induced degeneration in mice].

OBJECTIVES: To investigate the effect of a variety of kidney-tonifying Chinese medicines on thymus regeneration after acute degeneration in … intraperitoneal injections of rapamycin (1 mg·kg－1·d－1) for 5 consecutive days followed by 14 h of starvation to induce acute thymus degeneration. After successful modeling, in treatment groups ethanol extract of the fructus of Cnidium monnieri (L.) Cuss. (0.78 g·kg－1·d－1), fructus of Psoralea corylifolia (L.) (0.39 g·kg－1·d－1), fructus of Rubus chingii Hu …

Role of autophagy in cholangiocarcinoma: Pathophysiology and implications for therapy.

Cholangiocarcinoma (CCA) is a malignant tumour of the biliary system that originates from the neoplastic transformation of cholangiocytes. CCA is characterized by late diagnosis and poor outcome, with surgery considered as the last option for management. Autophagy is a physiological lysosomal degradation process, essential for cellular homeostasis and ubiquitous in all eukaryotic cells. Several studies have reported a potential involvement of autophagy in cancer, but it remains unclear whether activation of this process represents a survival mechanism of cancer cells. In the present review, we

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… Among the methods to induce autophagy, starvation is the most potent physiological inducer, which exerts effects both in vivo and in vitro . … QBC939 cells subjected to serum starvation responded with acetylation of FOXO1 (AcFOXO1) and subsequent interaction with Atg7, leading to autophagy activation. …

[Integrative transcriptomics-metabolomics approach to identify metabolic pathways regulated by glutamine synthetase activity].

Glutamine synthetase (GS), the only enzyme responsible for de novo glutamine synthesis, plays a significant role in cancer progression. As a … nt cells, the increased expression of ATF4 was accompanied by pronounced stress caused by glutamine starvation. Thus, ARS upregulation may predominantly arise from increased ATF4 expression in GS-deficient cells. Additionally, transcriptomic analysis revealed the differential expression of specific genes, regardless of GS activity, suggesting that GS is invo …

Resistance to apoptosis and autophagy leads to enhanced survival in Sertoli cells.

STUDY QUESTION: What is the underlying mechanism of Sertoli cell (SC) resistance to cell death? SUMMARY ANSWER: High expression of prosurvi … ificantly higher in SC compared to PTC at both mRNA and protein levels. Furthermore, after nutrient starvation, autophagy signaling was initiated in SC as observed by decreased levels of phosphorylated UNC- 51-like kinase -1 (ULK1). However, levels of light chain 3 II (LC3 II) and sequestosome1 (SQSTM1) remained unchanged, indicating blockade of the autophag …

Amino acids metabolism: a potential target for cancer treatment.

Metabolic reprogramming of amino acids has been recognized as a significant characteristic in various types of cancers. Numerous studies have indicated that the metabolic reprogramming of amino acids in tumors significantly supports certain malignant behaviors, including tumor proliferation, survival, invasion, and even immune escape. Amino acids can provide biomolecules such as nucleotides and glutathione (GSH) for tumors, and the bioavailability of amino acids influences tumor progression. Meanwhile, as essential metabolites, amino acids are closely associated with immune cell activation and

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… Autophagy suppresses tumor growth In certain contexts, excessive or prolonged activation of autophagy triggered by severe amino acid starvation surpasses its protective capacity and induces cancer cell death. … Interestingly, glutamine starvation may have more direct consequences on tumor cell survival than T cells [ 136 ]. Studies have shown that glutamine deprivation can sensitize cancer cells to radiotherapy. …

The Impact of Ketogenic Nutrition on Obesity and Metabolic Health: Mechanisms and Clinical Implications.

The ketogenic diet (KD) has recently gained increasing popularity. This high-fat, adequate-protein, and carbohydrate-poor eating pattern leads to nutritional ketosis. The KD has long been known for its antidiabetic and antiepileptic effects and has been used therapeutically in these contexts. Recently, the KD, due to its effectiveness in inducing weight loss, has also been proposed as a possible approach to treat obesity. Likewise, a KD is currently explored as a supporting element in the treatment of obesity-associated metabolic disorders and certain forms of cancer. Here, we discuss the meta

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… The figure was created with BioRender.com Prolonged Fasting and Starvation Starvation is defined as a prolonged fasting (>7 days) and can theoretically be prolonged for weeks (or even months) in humans. 52 At the beginning of a starvation period, glucose is obtained from the breakdown of glycogen stores … Such reprogramming underlies myocardial energy starvation, contributing to the pathogenesis of heart failure. …

EXPERIMENTS ON THE EFFECTS OF INJECTION OF EGG-ALBUMEN AND SOME OTHER PROTEIDS.

THE CONCLUSIONS WHICH WE DERIVE FROM OUR OBSERVATIONS ARE AS FOLLOWS: 1. The excretion of injected, egg-albumen as such is in no case comple … The total nitrogen excretion is increased beyond the amount of nitrogen introduced as albumen. 13. Starvation appears to cause an increase in the ratio of the urea to the total nitrogen of the urine. 14. The effects of intravenous injection of egg-albumen on circulation and respiration do not differ from those of an equivalent injection of the solvent. Albu …

Malnutrition-related hyperammonemic encephalopathy presenting with burst suppression: a case report.

BACKGROUND: Hyperammonemia is a common cause of metabolic encephalopathy, mainly related to hepatic cirrhosis. Numerous nonhepatic etiologies exist but they are infrequent and not well known, thus, leading to misdiagnosis and inadequate care. Electroencephalography has a proven diagnostic and prognostic role in comatose patients. Burst suppression is a preterminal pattern found in deep coma states and is rarely associated with metabolic causes. CASE PRESENTATION: We report the case of an 81-year-old Caucasian man presenting with rapidly progressive somnolence and mutism. Soon after his arriva

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… Table 1 Mechanism leading to nonhepatic hyperammonemia: increased production and decreased metabolism Overproduction Undermetabolism Excessive protein supply (enteral or parenteral) Portosystemic shunting Muscles catabolism: cachexia, starvation, seizure Medications interfering with urea cycle: valproic … disorders Hematological malignancies: multiple myeloma, leukemia Table 1 Mechanism leading to nonhepatic hyperammonemia: increased production and decreased metabolism Overproduction | Undermetabolism Excessive protein supply (enteral or parenteral) | Portosystemic shunting Muscles catabolism: cachexia, starvation …

Fasting-Mimicking Diet Inhibits Autophagy and Synergizes with Chemotherapy to Promote T-Cell-Dependent Leukemia-Free Survival.

Fasting mimicking diets (FMDs) are effective in the treatment of many solid tumors in mouse models, but their effect on hematologic malignancies is poorly understood, particularly in combination with standard therapies. Here we show that cycles of a 3-day FMD given to high-fat-diet-fed mice once a week increased the efficacy of vincristine to improve survival from BCR-ABL B acute lymphoblastic leukemia (ALL). In mice fed a standard diet, FMD cycles in combination with vincristine promoted cancer-free survival. RNA seq and protein assays revealed a vincristine-dependent decrease in the expressi

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… In Vitro Short-Term Starvation Reduces Cell Proliferation of Mouse and Human Leukemia Cells and Inhibits Autophagy We investigated the in vitro effects of short-term starvation (STS) on mouse (8093, M-ALL) and human (BV173, H-ALL) ALL cell lines grown under normal culture media (CTRL) or fasting-mimicking … Starvation, Stress Resistance, and Cancer. Trends Endocrinol. Metab. 2018;29:271–280. doi: 10.1016/j.tem.2018.01.008. 24. Lee C., Safdie F.M., Raffaghello L., Wei M., Madia F., Parrella E., Hwang D., Cohen P., Bianchi G., Longo V.D. …

Myeloid Cell-Derived Arginase in Cancer Immune Response.

Amino acid metabolism is a critical regulator of the immune response, and its modulating becomes a promising approach in various forms of immunotherapy. Insufficient concentrations of essential amino acids restrict T-cells activation and proliferation. However, only arginases, that degrade L-arginine, as well as enzymes that hydrolyze L-tryptophan are substantially increased in cancer. Two arginase isoforms, ARG1 and ARG2, have been found to be present in tumors and their increased activity usually correlates with more advanced disease and worse clinical prognosis. Nearly all types of myeloid

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… How L-arg starvation selectively impairs CD3ζ expression still remains unclear. L-arg starvation of human T-cells did not affect the degradation of CD3ζ in proteasome or lysosomes ( 218 ). … Mechanisms of arginine-starvation sensing in immune cells are still unclear. …

Proteomic analysis of MSC-derived apoptotic vesicles identifies Fas inheritance to ameliorate haemophilia a via activating platelet functions.

Apoptotic vesicles (apoVs) are apoptotic cell-derived nanosized vesicles that play a crucial role in multiple pathophysiological settings. However, their detailed characteristics, specific surface markers, and biological properties are not fully elucidated. In this study, we compared mesenchymal stem cell (MSC)-derived apoVs and exosomes from three different types of MSCs including human bone marrow MSCs (hBMSCs), human adipose MSCs (hASCs), and mouse bone marrow MSCs (mBMSCs). We established a unique protein map of MSC-derived apoVs and identified the differences between apoVs and exosomes in

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… Besides, we also used two other models of stress‐induced apoptosis (H 2 O 2 and starvation) to further validate the main findings. … Particularly, we also used two other models of stress‐induced apoptosis (H 2 O 2 and starvation) to further validate the main findings. We showed that apoVs derived from starvation, H 2 O 2 , and STS induction exhibited similar size distribution and membrane potential. …

Насколько общим является гиперкортизолизм у пациентов с гипертензией? Факторы риска, эпидемиология и диагностика.

Эндогенный гиперкортизолизм (ЭГК) является недооцененным и клинически значительным фактором гипертонии, особенно резистентной гипертонии. После того, как EHC считается редким субъектом, он теперь воспринимается как спектр избытка кортизола, связанного с неблагоприятными кардиометаболическими результатами и ущербом, причиненным мишени. Недавно проведенные широкомасштабные исследования свидетельствуют о значительном увеличении распространенности ЭГК среди пациентов с устойчивой гипертонией и трудноконтролируемым диабетом, зачастую в отсутствие классических особенностей кушингоида. В настоящем об

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… Requires 2 step testing (pill intake at 11 PM, testing at 8 AM next day) Inconsistent use in clinical practise Excessive alcohol consumption Pregnancy and oral contraceptives Advanced renal failure Severe neuropsychiatric disease Starvation/malnutrition Night shift work Severe untreated sleep … Severe neuropsychiatric disorders, particularly major depressive disorder with psychotic features, as well as starvation, malnutrition and anorexia nervosa may also produce false positives. …

Pharmacological interventions for non-alcohol related fatty liver disease (NAFLD): an attempted network meta-analysis.

BACKGROUND: Non-alcohol related fatty liver disease (commonly called non-alcoholic fatty liver disease (NAFLD)) is liver steatosis in the absence of significant alcohol consumption, use of hepatotoxic medication, or other disorders affecting the liver such as hepatitis C virus infection, Wilson's disease, and starvation. NAFLD embraces the full spectrum of disease from pure steatosis (i.e. uncomplicated fatty liver) to non-alcoholic steatohepatitis (NASH), via NASH-cirrhosis to cirrhosis. The optimal pharmacological treatment for people with NAFLD remains uncertain. OBJECTIVES: To assess the …

Cellular and molecular mechanisms of muscle atrophy.

Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of co

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… TRAF6 knockout mice are resistant to muscle loss induced by denervation, cancer or starvation ( Kumar et al., 2012 ; Paul et al., 2012 ; Paul et al., 2010 ). The mechanism of this protection involves both direct and indirect effects of TRAF6 on protein breakdown. … Indeed, JunB can block myofiber atrophy of denervated tibialis anterior muscles and cultured myotubes induced by FoxO3 overexpression, dexamethasone treatment or starvation. …

Radiotherapy-induced oxidative stress and fibrosis in breast cancer are suppressed by vactosertib, a novel, orally bioavailable TGF-β/ALK5 inhibitor.

Radio-resistance resulting from radiotherapy-induced fibrosis is a major clinical obstacle in breast cancer treatment because it typically leads to cancer recurrence, treatment failure, and patient death. Transforming growth factor-β (TGF-β) is a key signal messenger in fibrosis, which plays an important role in radiation-induced fibrosis and cancer stem cell (CSC) development, may be mediated through the generation of oxidative stress. This study was conducted to confirm the efficacy of vactosertib, a TGF-β/ALK5 inhibitor, as a potent inhibitor in radiation-induced oxidative stress generation

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… The cells were incubated with serum-reduced (0.2% FBS) medium for 16 h for starvation and irradiated with 10 Gy with or without 30-min pretreatment with 100 nM vactosertib. … The cells were incubated with serum-reduced (0.2% FBS) medium for 16 h for starvation. …

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma.

Autophagy is a multistep catabolic process through which misfolded, aggregated or mutated proteins and damaged organelles are internalized in membrane vesicles called autophagosomes and ultimately fused to lysosomes for degradation of sequestered components. The multistep nature of the process offers multiple regulation points prone to be deregulated and cause different human diseases but also offers multiple targetable points for designing therapeutic strategies. Cancer cells have evolved to use autophagy as an adaptive mechanism to survive under extremely stressful conditions within the tumo

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… FOXO1 expression and transcriptional activity are involved in promoting cellular autophagy, and the interaction of acetylated FOXO1 with ATG7 regulates basal and starvation-induced autophagy in CCA cells [ 30 ]. … In CCA models, CQ attenuates invasive activity of CCA cells under starvation, reducing TGF-β1-induced CCA cell invasion [ 134 ] and sensitizing resistant CCA cells to cisplatin [ 135 ]. …

Снимок новаторского подхода к комплексному преподаванию медицинской биохимии в рамках учебной программы для оценки результатов.

Медицинская биохимия (МБ) обычно преподается в начале медицинской программы, в которой практически отсутствует клинический контекст. Время родов и устаревшие методы обучения изображают БМ в негативном свете, ограничивая понимание его важности в медицинской практике. Для решения этой проблемы авторы разработали спирально интегрированный подход к преподаванию этой темы, в рамках которого основные темы, связанные с БМ, намеренно переплетаются по всей учебной программе, предшествующей стыковке, что позволяет учащимся пересматривать и углублять свое понимание материалов в все более клинических и ме

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… Teaching “glucose and lipid metabolism” with an integrated approach Teaching “glucose and lipid metabolism” with an integrated approach Initial introduction of glucose and lipid metabolism in the context of “Important Metabolic States” of the body Fasting, fed, and starvation states are central metabolic … Emphasizing the roles of glycogenolysis and gluconeogenesis in maintaining blood glucose homeostasis during fasting and early starvation, along with the hormonal regulation of these pathways by glucagon and epinephrine, supports high-yield, clinically grounded integration across biochemistry, cell biology …

Prevalence of low alkaline phosphatase activity in laboratory assessment: Is hypophosphatasia an underdiagnosed disease?

BackgroundTissue-nonspecific alkaline phosphatase (TNSALP) encoded by the ALPL gene is of particular importance for bone mineralization. Mutation in the ALPL gene can lead to persistent low ALP activity resulting in the rare disease Hypophosphatasia (HPP) that is characterized by disturbed bone and dental mineralization. While severe forms are extremely rare with an estimated prevalence of 1/100.000, recent studies suggest that moderate form caused by heterozygous mutations are much more frequent with an estimated prevalence of 1/508. The purpose of this study was to estimate the prevalence of

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… from (13) Causes of low ALP activity Hypophosphatasia (HPP) Osteogenesis imperfecta Cleidocranial dysplasia Mseleni joint disease Vitamin D intoxication Multiple myeloma Wilson's disease Vitamin C deficiency hypothyroidism Zn++ or Mg++ deficiency Cushing's syndrome Milk-alkali syndrome Celiac disease Starvation … from (13) Causes of low ALP activity Hypophosphatasia (HPP) Osteogenesis imperfecta Cleidocranial dysplasia Mseleni joint disease Vitamin D intoxication Multiple myeloma Wilson's disease Vitamin C deficiency hypothyroidism Zn++ or Mg++ deficiency Cushing's syndrome Milk-alkali syndrome Celiac disease Starvation …

CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers.

CHAC1, an essential regulator of oxidative stress and ferroptosis, is increasingly recognized for its significant roles in these cellular processes and its impact on various human diseases and cancers. This review aims to provide a comprehensive overview of CHAC1's molecular functions, regulatory mechanisms, and effects in different pathological contexts. Specifically, the study objectives are to elucidate the biochemical pathways involving CHAC1, explore its regulatory network, and discuss its implications in disease progression and potential therapeutic strategies. As a γ-glutamyl cyclotrans

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… However, this maintenance of mitochondrial activity under cysteine starvation is paradoxically detrimental to NSCLC cell survival, as it promotes ferroptosis. … CHAC1 enhances cystine-starvation-induced necroptosis and ferroptosis in human triple-negative breast cancer (TNBC) cells by degrading GSH. Under cystine starvation, the GCN2-eIF2α-ATF4 pathway is activated, leading to an upregulation of CHAC1 expression. …

Reducing diagnostic delay in hypophosphatasia: a case series of 14 patients presenting to general rheumatology.

OBJECTIVES: Hypophosphatasia (HPP) is a rare genetic metabolic bone disease that can cause chronic pain and fractures. Its hallmark is a persistently low serum ALP. HPP is now recognised by many osteoporosis specialists, but other specialists, such as rheumatologists and primary care physicians, may be less aware of this condition, causing diagnostic delay and possible harm to these patients. Our objective was to highlight features that can reduce this delay. METHODS: We retrospectively analysed 14 patients that presented with musculoskeletal pain to general rheumatology clinic at St. George'

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… Cardiac bypass surgery Cushing syndrome Clofibrate therapy Hypothyroidism Improperly collected blood (oxalate, ethylenediaminetetraacetic acid) Inappropriate reference range Massive transfusion Multiple myeloma Milk-alkali syndrome Osteogenesis imperfecta, type 2 Profound anaemia Pernicious anaemia Starvation … bypass surgery Cushing syndrome | Clofibrate therapy Hypothyroidism | Improperly collected blood (oxalate, ethylenediaminetetraacetic acid) Inappropriate reference range | Massive transfusion Multiple myeloma | Milk-alkali syndrome Osteogenesis imperfecta, type 2 | Profound anaemia Pernicious anaemia | Starvation …