Understanding blood development and leukemia using sequencing-based technologies and human cell systems.

Our current understanding of human hematopoiesis has undergone significant transformation throughout the years, challenging conventional views. The evolution of high-throughput technologies has enabled the accumulation of diverse data types, offering new avenues for investigating key regulatory processes in blood cell production and disease. In this review, we will explore the opportunities presented by these advancements for unraveling the molecular mechanisms underlying normal and abnormal hematopoiesis. Specifically, we will focus on the importance of enhancer-associated regulatory networks and highlight the crucial role of enhancer-derived transcription regulation. Additionally, we will discuss the unprecedented power of single-cell methods and the progression in using in vitro human blood differentiation system, in particular induced pluripotent stem cell models, in dissecting hematopoietic processes. Furthermore, we will explore the potential of ever more nuanced patient profiling to allow precision medicine approaches. Ultimately, we advocate for a multiparameter, regulatory network-based approach for providing a more holistic understanding of normal hematopoiesis and blood disorders.

The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis.

The role of zinc in hematopoiesis is currently unclear. Here, SLC39A10 (ZIP10) is identified as a key zinc transporter in hematopoiesis. The results show that in zebrafish, Slc39a10 is a key regulator of the response to zinc deficiency. Surprisingly, both slc39a10 mutant zebrafish and hematopoietic Slc39a10-deficient mice develop a more severe form of impaired hematopoiesis than animals lacking transferrin receptor 1, a well-characterized iron gatekeeper, indicating that zinc plays a larger role than iron in hematopoiesis, at least in early hematopoietic stem cells (HSCs). Furthermore, it is shown that loss of Slc39a10 causes zinc deficiency in fetal HSCs, which in turn leads to DNA damage, apoptosis, and G1 cell cycle arrest. Notably, zinc supplementation largely restores colony formation in HSCs derived from hematopoietic Slc39a10-deficient mice. In addition, inhibiting necroptosis partially restores hematopoiesis in mouse HSCs, providing mechanistic insights into the requirement for zinc in mediating hematopoiesis. Together, these findings indicate that SLC39A10 safeguards hematopoiesis by protecting against zinc deficiency-induced necroptosis, thus providing compelling evidence that SLC39A10 and zinc homeostasis promote the development of fetal HSCs. Moreover, these results suggest that SLC39A10 may serve as a novel therapeutic target for treating anemia and zinc deficiency-related disorders.

Selenium Improves Bone Microenvironment-Related Hematopoiesis and Immunity in T-2 Toxin-Exposed Mice.

The T-2 toxin is one of the most frequent contaminants in the environment and agricultural production globally. It exerts a wide range of toxic effects. Selenium (Se), as an antioxidant, has the potential to be widely used to antagonize mycotoxin toxicity. To investigate the protective effects of Se on bone microenvironment (BM)-related hematopoiesis and immunity after T-2 toxin exposure, 36 male mice were treated with the T-2 toxin (1 mg/kg) and/or Se (0.2 mg/kg) by intragastric administration for 28 days. The results showed that Se alleviated T-2 toxin-induced cytopenia and splenic extramedullary hematopoiesis. Se also significantly relieved T-2 toxin-induced immunosuppression, as assessed by immune factors and lymphocytes. Furthermore, Se also attenuated oxidative stress and apoptosis and improved the BM in T-2 toxin-exposed mice. Therefore, Se improves BM-related hematopoiesis and immunity after T-2 toxin exposure. This study provides references for identifying the toxic mechanism and screening potential therapeutic drugs of the T-2 toxin.

Clinical and molecular characteristics associated with Vitamin C deficiency in myeloid malignancies; real world data from a prospective cohort.

Vitamin C is an essential vitamin that acts as a co-factor for many enzymes involved in epigenetic regulation in humans. Low vitamin C levels in hematopoietic stem cells (HSC) promote self-renewal and vitamin C supplementation retards leukaemogenesis in vitamin C-deficient mouse models. Studies on vitamin C levels in patients with myeloid malignancies are limited. We thus conducted a retrospective analysis on a prospective cohort of patients with myeloid malignancies on whom plasma vitamin C levels were measured serially at diagnosis and during treatment. Baseline characteristics including hematological indices, cytogenetics, and molecular mutations are described in this cohort. Among 64 patients included in our study, 11 patients (17%) had low vitamin C levels. We noted a younger age at diagnosis for patients with myeloid malignancies who had low plasma vitamin C levels. Patients with low plasma vitamin C levels were more likely to have acute myeloid leukemia compared to other myeloid malignancies. Low vitamin C levels were associated with ASXL1 mutations. Our study calls for further multi-institutional studies to understand the relevance of low plasma vitamin C level in myeloid neoplasms, the role of vitamin C deficiency in leukemogenesis, and the potential benefit of vitamin C supplementation.

Astaxanthin Protects against Hyperglycemia-Induced Oxidative and Inflammatory Damage to Bone Marrow and to Bone Marrow-Retained Stem Cells and Restores Normal Hematopoiesis in Streptozotocin-Induced Diabetic Mice.

Hyperglycemia has various adverse health effects, some of which are due to chronic oxidative and inflammatory impairment of bone marrow (BM), hematopoietic stem cells (HSCs), and mesenchymal stem cells (MSCs). Astaxanthin (ASTX) has been shown to ameliorate hyperglycemia-associated systemic complications and acute mortality, and this effect is partially associated with restoration of normal hematopoiesis. Here, the effects of ASTX on diabetes-induced complications in BM and BM stem cells were investigated, and the underlying molecular mechanisms were elucidated. Ten-week-old C57BL/6 mice received a single intraperitoneal injection of streptozotocin (STZ; 150 mg/kg) in combination with oral gavage of ASTX (12.5 mg/kg) for 30 or 60 consecutive days. Supplemental ASTX ameliorated acute mortality and restored the STZ-impaired bone mass accrual and BM microenvironment in STZ-injected mice. Oral gavage of ASTX suppressed osteoclast formation in the BM of STZ-injected mice. Specifically, supplementation with ASTX inhibited oxidative stress and senescence induction of BM HSCs and MSCs and ameliorated hematopoietic disorders in STZ-injected mice. These effects of ASTX were associated with BM restoration of angiopoietin 1, stromal cell-derived factor 1, ß-catenin, and Nrf2. Long-term ASTX gavage also recovered the STZ-induced dysfunction in migration, colony formation, and mineralization of BM-derived stromal cells. Further, a direct addition of ASTX exhibited direct and dose-dependent inhibition of osteoclastic activation without cytotoxic effects. Collectively, these results indicate that ASTX protects against diabetes-induced damage in the BM microenvironment in BM, HSCs, and MSCs and restores normal hematopoiesis and bone accrual in STZ-injected mice.

Sex and Circadian Timing Modulate Oxaliplatin Hematological and Hematopoietic Toxicities.

Oxaliplatin was nearly twice as hematotoxic, with optimal circadian timing differing by 6 h, in women as compared to men with colorectal cancers. Hence, we investigated sex- and timing-related determinants of oxaliplatin hematopoietic toxicities in mice. Body-weight loss (BWL), blood cell counts, bone marrow cellularity (BMC) and seven flow-cytometry-monitored hematopoietic progenitor populations were evaluated 72 h after oxaliplatin chronotherapy administration (5 mg/kg). In control animals, circadian rhythms of circulating white blood cells showed a peak at ZT5 in both sexes, whereas BMC was maximum at ZT20 in males and ZT13h40 in females. All BM progenitor counts presented robust rhythms with phases around ZT3h30 in females, whereas only three of them rhythmically cycled in males with a ≈ -6 h phase shift. In treated females, chronotoxicity rhythms occurred in BWL, WBC, BMC and all BM progenitors with the best timing at ZT15, ZT21, ZT15h15 and ZT14h45, respectively. In males, almost no endpoints showed circadian rhythms, BWL and WBC toxicity being minimal, albeit with a substantial drop in BM progenitors. Increasing dose (10 mg/kg) in males induced circadian rhythms in BWL and WBC but not in BM endpoints. Our results suggest complex and sex-specific clock-controlled regulation of the hematopoietic system and its response to oxaliplatin.

Deciphering the Effects of 2D Black Phosphorus on Disrupted Hematopoiesis and Pulmonary Immune Homeostasis Using a Developed Flow Cytometry Method.

As an emerging two-dimensional nanomaterial with promising prospects, mono- or few-layer black phosphorus (BP) is potentially toxic to humans. We investigated the effects of two types of BPs on adult male mice through intratracheal instillation. Using the flow cytometry method, the generation, migration, and recruitment of immune cells in different organs have been characterized on days 1, 7, 14, and 21 post-exposure. Compared with small BP (S-BP, lateral size at ∼188 nm), large BP (L-BP, lateral size at ∼326 nm) induced a stronger stress lymphopoiesis and B cell infiltration into the alveolar sac. More importantly, L-BP dramatically increased peripheral neutrophil (NE) counts up to 1.9-fold on day 21 post-exposure. Decreased expression of the CXCR4 on NEs, an important regulator of NE retention in the bone marrow, explained the increased NE release into the circulation induced by L-BP. Therefore, BP triggers systemic inflammation via the disruption of both the generation and migration of inflammatory immune cells.

The Hematopoietic Effect of Ninjinyoeito (TJ-108), a Traditional Japanese Herbal Medicine, in Pregnant Women Preparing for Autologous Blood Storage.

Background and Objectives: There are no reports showing the hematopoietic effect of TJ-108 on pregnant women. The aim of this study was to investigate the effect of TJ-108 on the hemoglobin and hematocrit levels, and white blood cell and platelet counts of pregnant women complicated with placenta previa who were managed with autologous blood storage for cesarean section. Materials and Methods: We studied two groups of patients who were complicated with placenta previa and who underwent cesarean delivery. Group A consisted of women who were treated with oral iron medication (100 mg/day), and Group B consisted of women who were treated with TJ-108 at a dose of 9.0 g per day, in addition to oral iron medication, from the first day of blood storage until the day before cesarean delivery. To evaluate the effect of TJ-108, the patients' red blood cell (RBC); Hb; hematocrit (Ht); white blood cell (WBC); and platelet count (PLT) levels were measured 7 days after storage and at postoperative days (POD) 1 and 5. Results: The study included 65 individuals, 38 in group A and 27 in group B. At the initial storage, a 0.2 g/dL reduction in Hb levels was observed, as compared to the initial Hb levels, in the TJ-108 treated patients, whereas a 0.6 g/dL reduction in Hb levels was observed in the non-TJ-108 treated group. On the other hand, regarding the second and subsequent storages, no significant difference was found in the decrease in the Hb levels of both groups. Conclusions: This study is the first report showing the effect of TJ-108 on improving anemia in pregnant women, presumably by its boosting effect on myelohematopoiesis. Therefore, the combined administration of both iron and TJ-108 is effective as a strategy for pregnant women at a high risk of PPH due to complications such as placenta previa.

Calcium carbide-induced derangement of hematopoiesis and organ toxicity ameliorated by cyanocobalamin in a mouse model.

BACKGROUND: Calcium carbide (CaC2) is a chemical primarily used in the production of acetylene gas. The misuse of CaC2 to induce fruit ripening is a global challenge with a potential adverse effects to human health. Additionally, CaC2 is known to contain some reasonable amount of arsenic and phosphorous compounds that are toxic and pose a danger to human health when ingested. The current study sought to characterize CaC2 toxicity and elucidate any protective effects by cyanocobalamin (vitamin B12), a well-established antioxidant and anti-inflammatory bio-molecule. Female Swiss white mice were randomly assigned into three groups; the first group was the control, while the second group was administered with CaC2. The third group received CaC2 followed by administration of vitamin B12. The mice were sacrificed at 60 days post treatment, hematological, biochemical, glutathione assay, cytokine ELISA and standard histopathology was performed. RESULTS: CaC2 administration did not significantly alter the mice body weight. CaC2 administration resulted in a significant decrease in packed cell volume (PCV), hemoglobin (Hb), red blood cells (RBCs) and RBC indices; indicative of CaC2-driven normochromic microcytic anaemia. Further analysis showed CaC2-driven leukopenia. Evidently, vitamin B12 blocked CaC2-driven suppression of PCV, Hb, RBCs and WBCs. Monocytes and neutrophils were significantly up-regulated by CaC2. CaC2-induced elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin signaled significant liver damage. Notably, vitamin B12 stabilized AST, ALT and bilirubin in the presence of CaC2, an indication of a protective effect. Histopathological analysis depicted that vitamin B12 ameliorated CaC2-driven liver and kidney injury. CaC2 resulted in the depletion of glutathione (GSH) levels in the liver; while in the brain, kidney and lungs, the GSH levels were elevated. CaC2 administration resulted in elevation of pro-inflammatory cytokines TNF-α and IFN-γ. Vitamin B12 assuaged the CaC2-induced elevation of these pro-inflammatory cytokines. CONCLUSIONS: These findings demonstrate for the first time that oral supplementation with vitamin B12 can protect mice against CaC2-mediated toxicity, inflammation and oxidative stress. The findings provide vital tools for forensic and diagnostic indicators for harmful CaC2 exposure; while providing useful insights into how vitamin B12 can be explored further as an adjunct therapy for CaC2 toxicity.

Effects of Soy-Whey Protein Nutritional Supplementation on Hematopoiesis and Immune Reconstitution in an Allogeneic Transplanted Mice.

Profound malnutrition and immunodeficiency are serious negative effects of radiotherapy and bone marrow transplantation for hematologic malignancy patients. This study aimed to evaluate the effects of nutritional supplementation with a soy-whey protein mixture on hematopoietic and immune reconstitution in an allogeneic transplant mouse model. Male BALB/c (H-2Kd) mice, 6-8 weeks-old, were divided randomly into five groups and then provided with different protein nutrition support. After 28 days, blood samples, bone marrow, spleen, and thymus were harvested to measure the effects. The results showed that soy-whey blended protein supplements promoted hematopoietic stem cell engraftment, body weight recovery, and the recovery of white blood cells, lymphocytes, and neutrophils; triggered the expansion of hematopoietic stem cells and progenitor cell pools by increasing the numbers of the c-kit+ progenitor, Lin-Sca1+c-kit+, short-term hematopoietic stem cells, and multipotent progenitors; enhanced thymus re-establishment and splenic subset recovery in both organ index and absolute number; improved overall nutritional status by increasing total serum protein, albumin, and globulin; protected the liver from radiation-induced injury, and increased antioxidant capacity as indicated by lower concentrations of alanine aminotransferase, aspartate aminotransferase, malondialdehyde, and 4-hydroxynonenal. This study indicated that soy-whey blended protein as important nutrients, from both plant and animal sources, had a greater positive effect on patients with hematological malignancies to accelerate hematopoiesis and immune reconstitution after bone marrow transplantation.

Mechanisms of Danggui Buxue Tang on Hematopoiesis via Multiple Targets and Multiple Components: Metabonomics Combined with Database Mining Technology.

This study aimed to explore the mechanism of action of Danggui Buxue Tang (DBT) with its multiple components and targets in the synergistic regulation of hematopoiesis. Mouse models of hematopoiesis were established using antibiotics. Metabolomics was used to detect body metabolites and enriched pathways. The active ingredients, targets, and pathways of DBT were analyzed using system pharmacology. The results of metabolomics and system pharmacology were integrated to identify the key pathways and targets. A total of 515 metabolites were identified using metabolomics. After the action of antibiotics, 49 metabolites were markedly changed: 23 were increased, 26 were decreased, and 11 were significantly reversed after DBT administration. Pathway enrichment analysis showed that these 11 metabolites were related to bile secretion, cofactor biosynthesis, and fatty acid biosynthesis. The results of the pharmacological analysis showed that 616 targets were related to DBT-induced anemia, which were mainly enriched in biological processes, such as bile secretion, biosynthesis of cofactors, and cholesterol metabolism. Combined with the results of metabolomics and system pharmacology, we found that bile acid metabolism and biotin synthesis were the key pathways for DBT. Forty-two targets of DBT were related to these two metabolic pathways. PPI analysis revealed that the top 10 targets were CYP3A4, ABCG2, and UGT1A8. Twenty-one components interacted with these 10 targets. In one case, a target corresponds to multiple components, and a component corresponds to multiple targets. DBT acts on multiple targets of ABCG2, UGT1A8, and CYP3A4 through multiple components, affecting the biosynthesis of cofactors and bile secretion pathways to regulate hematopoiesis.

A glyphosate-based herbicide disrupted hematopoiesis and induced organ toxicities, ameliorated by vitamin B12 in a mouse model.

Glyphosate-based herbicides (GBH) are widely used worldwide. Their negative impact on human health is a matter of debate by regulatory bodies and the public. The present study sought to determine the impact of a GBH on the vital organs; and the potential protective effects of vitamin B12 (cyanocobalamin) supplementation. Sixty white Swiss mice were randomly assigned to five treatment groups, each containing twelve mice. Group one represented the normal control; Group two mice were treated with 375 mg/kg of GBH for 56 days; Group three mice received 10 mg/kg of cyanocobalamin for 56 days; Group four mice were administered with 375 mg/kg of GBH and 10 mg/kg cyanocobalamin for 56 days and Group five received 10 mg/kg cyanocobalamin first for 7 days, then continued thereafter co-administered together with 375 mg/kg of GBH for 56 days). Oral administration of GBH induced severe anemia in mice, which was attenuated by cyanocobalamin. Moreover, GBH resulted in a very significant alteration of platelets, WBCs, and its sub-types. Once again, cyanocobalamin stabilized the levels of platelets and WBCs in the presence of GBH. GBH-induced elevation of triglycerides and HDL was nullified by the administration of cyanocobalamin. Further studies showed evidence for GBH-induced inflammation represented by an imbalance in serum levels of the TNF-α: IL-10 and IFN-γ ratios. The GBH severely depleted GSH levels in the liver. A GBH-induced rise in GSH in the kidney, lungs and brain was noted; and is an indicator of antioxidant capacity enhancement in response to a GBH-induced oxidant challenge. Moreover, cyanocobalamin supplementation abrogated GBH-induced oxidative stress as depicted by stabilized GSH levels in the liver, kidney, lungs, and brain. In the presence of cyanocobalamin, the GBH-induced liver injury depicted by elevation of AST, ALT, and bilirubin, was attenuated. From the results, we conclude that the capacity of cyanocobalamin to assuage GBH-induced inflammatory responses, hepatotoxicity, and hematological alteration as well as oxidative stress may be attributable to its antioxidant and anti-inflammatory properties. The current findings provide a solid foundation for further scrutiny of this phenomenon, with vital implications in GBH exposure and the role of potent antioxidant supplementation in the management of GBH-induced toxicity.

An oncogenic enhancer encodes selective selenium dependency in AML.

Deregulation of transcription is a hallmark of acute myeloid leukemia (AML) that drives oncogenic expression programs and presents opportunities for therapeutic targeting. By integrating comprehensive pan-cancer enhancer landscapes with genetic dependency mapping, we find that AML-enriched enhancers encode for more selective tumor dependencies. We hypothesized that this approach could identify actionable dependencies downstream of oncogenic driver events and discovered a MYB-regulated AML-enriched enhancer regulating SEPHS2, a key component of the selenoprotein production pathway. Using a combination of patient samples and mouse models, we show that this enhancer upregulates SEPHS2, promoting selenoprotein production and antioxidant function required for AML survival. SEPHS2 and other selenoprotein pathway genes are required for AML growth in vitro. SEPHS2 knockout and selenium dietary restriction significantly delay leukemogenesis in vivo with little effect on normal hematopoiesis. These data validate the utility of enhancer mapping in target identification and suggest that selenoprotein production is an actionable target in AML.

Steamed Panax notoginseng attenuates renal anemia in an adenine-induced mouse model of chronic kidney disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng (PN) (Burk.) F. H. Chen is a medicinal herb used to treat blood disorders since ancient times, of which the steamed form exhibits the anti-anemia effect and acts with a "blood-tonifying" function according to the traditional use. However, its pharmacological effect and mechanism on alleviating renal anemia (RA) are still unclear. AIMS OF THE STUDY: The study aims to investigate the effect of steamed Panax notoginseng (SPN) to attenuate RA and its underlying mechanism based on the model of adenine-induced RA mice. MATERIALS AND METHODS: Seventy mice were randomly divided into seven groups of ten: the control group, model group, the erythropoietin (EPO) group, the Fufang E'jiao Jiang (FEJ) group, the high-dose steamed PN (H-SPN) group, the middle-dose steamed PN (M-SPN) group, and the low-dose steamed PN (L-SPN) group. The adenine induction RA model was applied to assess the "blood enriching" function of SPN. The blood routine indexes, erythrocyte fragility, pathologic morphology of kidney tissue and the expression levels of related cytokines and proteins in the mice were detected after 3-week administration with SPN and positive drugs. RESULTS: Our study provided evidences that SPN could ameliorate RA. Compared with the control group, SPN could attenuate RA by significantly increasing the numbers of peripheral blood cells (p < 0.01), improving the erythrocyte fragility (p < 0.01), and restoring the expression of EPO mRNA in the kidneys and EPO receptor mRNA in bone marrow nucleated cells. The expression of TGF-ß1 mRNA was declined and the expression of HGF mRNA was significantly increased in a dose-dependent way after the treatment of SPN. Additionally, the expression of Bcl-2 and Bcl-2/Bax ratio in the kidneys were significantly increased. In contrast, there was a highly significant decrease in the expression of Bax (p < 0.01), following SPN treatment. CONCLUSION: SPN could alleviate RA by promoting the overall hematopoiesis and inhibiting the progress of renal injury in mice.

Patient blood management when blood is not an option: a report of two cases.

There are many patients who refuse to receive blood transfusions for religious or other reasons. Bloodless medicine and surgery are no longer new concept, but patients who refuse blood transfusion are still transferred to the bloodless center, regardless of patients' intention, for treatment. Here, we discuss the need for patient blood management when blood is not an option to treat them. Two patients of advanced age were transferred to our bloodless center due to refusal of transfusion. They are Jehovah's Witnesses and refused to receive blood transfusion despite life-threatening anemia and severe underlying diseases. Patient blood management protocols including iron supplementation, subcutaneous erythropoietin, folic acid and vitamin B were implemented to improve hematopoiesis, and supportive care was also performed to treat underlying diseases. Levels of Hemoglobin/Hematocrit and their symptom gradually improved about a week after treatment, and their condition had gradually stabilized. They were discharged safely. We treated patients of advanced age with severe underlying diseases and life-threatening anemia using patient blood management due to refusal of a blood transfusion. The patient blood management may be a useful alternative strategy, which meet the needs of patients who refuse blood transfusions as well as the need to reduce the use of blood products due to limited supply.

The Effect of Pre-operative Autologous Blood Donation on Bone Marrow Hematopoietic Functions in Rabbits after Hepatectomy.

BACKGROUND: Pre-operative autologous blood donation (PABD) is one of the most widely distributed autologous blood donation means, which has positive effects on erythropoiesis. However, whether PABD can stimulate the bone marrow hematopoiesis after hepatectomy has not been reported. METHODS: Totally 80 New Zealand rabbits were randomly divided into 4 groups that included control group, surgery group, hemodilutional autotransfusion (HA) group and PABD group. Automatic reticulocyte examination was performed to detect the content of reticulocyte and immature reticulocyte fractions (IRF). Flow cytometric analysis was employed to monitor the level of CD34+ cells and the cell cycle status. Southern blotting was conducted to determine the telomere length of CD34+ cells. RESULTS: The content of high fluorescence reticulocytes (HFR) and IRF was decreased at 6 h and 24 h after autotransfusion. However, the level of CD34+ cells was upregulated after PABD. Cell cycle status analysis revealed that the majority of the CD34+ cells in HA and PABD group were maintained in G0/G1 phase. The telomere length in HA and PABD group was shortened than that of the control group and surgery group. CONCLUSION: PABD could promote the bone marrow hematopoietic functions in rabbits after hepatectomy via stimulating proliferation of CD34+ cells and shortening the telomere length of CD34+ cells, but the content of HFR was not increased immediately because of the stuck of CD34+ cells in the G0/G1 phase.

Is 6-Shogaol an Effective Phytochemical for Patients With Lower-risk Myelodysplastic Syndrome? A Narrative Review.

Myelodysplastic syndrome (MDS) evolves due to genomic instability, dysregulated signaling pathways, and overproduction of inflammatory markers. Reactive oxygen species contribute to the inflammatory response, which causes gene damage, cellular remodeling, and fibrosis. MDS can be a debilitating condition, and management options in patients with MDS aim to improve cytopenias, delay disease progression, and enhance quality of life. High serum ferritin levels, a source of iron for reactive oxygen species production, correlate with a higher risk of progression to acute myeloid leukemia, and iron overload is compounded by blood transfusions given to improve anemia. 6-shogaol is a natural phenolic compound formed when ginger is exposed to heat and/or acidic conditions, and it has been shown to possess anti-tumor activity against leukemia cell lines and antioxidant effects. This narrative review assessed the potential benefits of this phytochemical in lower-risk MDS patients through examining the current evidence on the pharmacological and therapeutic properties of ginger and 6-shogaol.

Enriched clonal hematopoiesis in seniors with dietary vitamin C inadequacy.

BACKGROUND: The anti-cancer effect of vitamin C (VC) has long been speculated, but studies yielded inconsistency. Recent studies reported that supraphysiological concentration of VC have therapeutic or prevention effects for myeloid malignancies with certain mutation signatures. There was a notable proportion of DAT (i.e., DNMT3A, ASXL1, and TET2) and dozens of other genes that mutate in age-related clonal hematopoiesis (ARCH). METHODS AND RESULTS: Through analyzing the plasma VC concentration and mutations of 21 genes in 215 senior volunteers, we revealed that ARCH is significantly associated with dietary plasma VC concentrations, especially TET2 mutations and non-DAT mutations. CONCLUSION: This study firstly disclosed the significant association between VC inadequacy and ARCH in the senior population. It provides evidence that physiological VC concentration has ARCH prevention effect. It will illuminate future explorations on the oral VC supplement in maintaining sound hematopoiesis, reversal ARCH, adjuvant therapy for myeloid malignancies, and prevention of other ARCH related comorbidities.

The increasing hematopoietic effect of the combined treatment of Korean Red Ginseng and Colla corii asini on cyclophosphamide-induced immunosuppression in mice.

BACKGROUND: Hematopoiesis is the production of blood cells from hematopoietic stem cells (HSCs) that reside in the bone marrow. Cyclophosphamide (CTX) is a chemotherapy drug that suppresses the immune system. Korean Red Ginseng (KRG) and Colla corii asini (CCA) have been traditionally used for boosting the immune system. METHODS: HSCs in the bone marrow, and immune cell subtype in splenocytes, PBMCs, and thymocytes were investigated. Serum levels of hematopoietic-related markers were analyzed using ELISA. Protein expression in spleen tissue was analyzed using western blot analysis. Hematoxylin & eosin staining in the femurs of mice were also conducted. RESULTS: The combination of KRG and CCA with a ratio of 3:2 increased HSCs, CD3 and CD8+ T cells in the circulation, and CD3 T cells in the spleen. A ratio of 2:3 (KRG:CCA) increased the thymic regulatory T cells and recovered the CD3 T cells in the spleen and circulation while recovering proteins in the JAK-STAT pathway in the spleen. Overall, blood cell population and differentiating factors vital for cell differentiation were also significantly recovered by all combinations especially in ratios of 3:2 and 2:3. CONCLUSION: A ratio of 3:2 (KRG:CCA) is the most ideal combination as it recovered the HSC population in the bone marrow of mice.

PAC1 Receptor Mediates Electroacupuncture-Induced Neuro and Immune Protection During Cisplatin Chemotherapy.

Platinum-based chemotherapy is an effective treatment used in multiple tumor treatments, but produces severe side effects including neurotoxicity, anemia, and immunosuppression, which limits its anti-tumor efficacy and increases the risk of infections. Electroacupuncture (EA) is often used to ameliorate these side effects, but its mechanism is unknown. Here, we report that EA on ST36 and SP6 prevents cisplatin-induced neurotoxicity and immunosuppression. EA induces neuroprotection, prevents pain-related neurotoxicity, preserves bone marrow (BM) hematopoiesis, and peripheral levels of leukocytes. EA activates sympathetic BM terminals to release pituitary adenylate cyclase activating polypeptide (PACAP). PACAP-receptor PAC1-antagonists abrogate the effects of EA, whereas PAC1-agonists mimic EA, prevent neurotoxicity, immunosuppression, and preserve BM hematopoiesis during cisplatin chemotherapy. Our results indicate that PAC1-agonists may provide therapeutic advantages during chemotherapy to treat patients with advanced neurotoxicity or neuropathies limiting EA efficacy.