Effect of Post-transplant Dietary Restriction on Hematopoietic Reconstitution and Maintenance of Reconstitution Capacity of Hematopoietic Stem Cells.

Hematopoietic cell transplantation (HCT) is an important therapy for many hematological malignancies as well as some non-malignant diseases. Post-transplant hematopoiesis is affected by multiple factors, and the mechanisms of delayed post-transplant hematopoiesis remain poorly understood. Patients undergoing HCT often suffer from significantly reduced food intake due to complications induced by preconditioning treatments. Here, we used a dietary restriction (DR) mouse model to study the effect of post-transplant dietary reduction on hematopoiesis and hematopoietic stem cells (HSCs). We found that post-transplant DR significantly inhibited both lymphopoiesis and myelopoiesis in the primary recipient mice. However, when bone marrow cells (BMCs) from the primary recipient mice were serially transplanted into secondary and tertiary recipient mice, the HSCs derived from the primary recipient mice, which were exposed to post-transplant DR, exhibited a much higher reconstitution capacity. Transplantation experiments with purified HSCs showed that post-transplant DR greatly inhibited hematopoietic stem cell (HSC) expansion. Additionally, post-transplant DR reshaped the gut microbiotas of the recipient mice, which inhibited inflammatory responses and thus may have contributed to maintaining HSC function. Our findings may have important implications for clinical work because reduced food intake and problems with digestion and absorption are common in patients undergoing HCT.

Dietary restriction rescues 5-fluorouracil-induced lethal intestinal toxicity in old mice by blocking translocation of opportunistic pathogens.

Chemotherapy remains a major treatment for malignant tumors, yet the application of standard dose intensity chemotherapy is limited due to the side effects of cytotoxic drugs, especially in old populations. The underlying mechanisms of cytotoxicity and strategies to increase the safety and tolerance of chemotherapy remain to be explored. Using 5-fluorouracil (5-FU), a cornerstone chemotherapeutic drug, we demonstrate that the main cause of death in ad libitum (AL) fed mice after 5-FU chemotherapy was infection caused by translocation of intestinal opportunistic pathogens. We show that these opportunistic pathogens greatly increase in the intestine after chemotherapy, which was closely related to loss of intestinal lysozyme. Of note, two weeks of dietary restriction (DR) prior to chemotherapy significantly protected the loss of lysozyme and increased the content of the beneficial Lactobacillus genera, resulting in a substantial inhibition of intestinal opportunistic pathogens and their translocation. The rescue effect of DR could be mimicked by Lysozyme or Lactobacillus gavage. Our study provides the first evidence that DR achieved a comprehensive protection of the intestinal physical, biological and chemical barriers, which significantly improved the overall survival of 5-FU-treated mice. Importantly, the above findings were more prominent in old mice. Furthermore, we show that patients over 65 years old have enriched opportunistic pathogens in their gut microbiota, especially after 5-FU based chemotherapy. Our study reveals important mechanisms for the poor chemotherapy tolerance of the elderly population, which can be significantly improved by short-term DR. This study generates new insights into methods for improving the chemotherapeutic prognosis by increasing the chemotherapy tolerance and safety of patients with malignant tumors.

A review on the transformation of birnessite in the environment: Implication for the stabilization of heavy metals.

Birnessite is ubiquitous in the natural environment where heavy metals are retained and easily transformed. The surface properties and structure of birnessite change with the changes in external environmental conditions, which also affects the fate of heavy metals. Clarifying the effect and mechanism of the birnessite phase transition process on heavy metals is the key to taking effective measures to prevent and control heavy metal pollution. Therefore, the four transformation pathways of birnessite are summarized first in this review. Second, the relationship between transformation pathways and environmental conditions is proposed. These relevant environmental conditions include abiotic (e.g., co-existing ions, pH, oxygen pressure, temperature, electric field, light, aging, pressure) and biotic factors (e.g., microorganisms, biomolecules). The phase transformation is achieved by the key intermediate of Mn(III) through interlayer-condensation, folding, neutralization-disproportionation, and dissolution-recrystallization mechanisms. The AOS (average oxidation state) of Mn and interlayer spacing are closely correlated with the phase transformation of birnessite. Last but not least, the mechanisms of heavy metals immobilization in the transformation process of birnessite are summed up. They involve isomorphous substitution, redox, complexation, hydration/dehydration, etc. The transformation of birnessite and its implication on heavy metals will be helpful for understanding and predicting the behavior of heavy metals and the crucial phase of manganese oxides/hydroxides in natural and engineered environments.

Dietary Restriction Delays But Cannot Heal Irradiation-Induced Hair Graying by Preserving Hair Follicle Stem Cells in Quiescence.

DNA damage represents one of the cell intrinsic causes of stem cell aging, which leads to differentiation-induced removal of damaged stem cells in skin and blood. Dietary restriction (DR) retards aging across various species, including several strains of laboratory mice. Whether, DR has the potential to ameliorate DNA damage-driven stem cell exhaustion remains incompletely understood. In this study, we show that DR strongly extends the time to hair graying in response to γ-irradiation (ionizing radiation [IR])-induced DNA damage of C57BL/6 J mice. The study shows that DR prolongs resting phase of hair follicles. DR-mediated prolongation of hair follicle stem cell (HFSC) quiescence blocks hair growth and prevents the depletion of HFSCs and ckit+ melanoblasts in response to IR. However, prolongation of HFSC quiescence also correlates with a suppression of DNA repair and cannot prevent melanoblast loss and hair graying in the long run, when hair cycling is reinitiated even after extended periods of time. Altogether, these results support a model indicating that nutrient deprivation can delay but not heal DNA damage-driven extinction of melanoblasts by stalling HFSCs in a prolonged state of quiescence coupled with inhibition of DNA repair. Disconnecting these two types of responses to DR could have the potential to delay stem cell aging.

[Effects of electroacupuncture on the blood-brain-barrier and proinflammatory cytokine IL-1ß and IL-18 in the hippocampus of rats with vascular dementia].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on blood-brain barrier (BBB) permeability and proinflammatory cytokines interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in the hippocampus of vascular dementia (VD) rats, so as to explore the mechanism of EA on treatment of VD. METHODS: SD male rats were randomly divided into sham operation, model, and EA groups, with 15 rats in each group. The VD rat model was established by permanently occlusion of the bilateral middle cerebral artery. Rats of the EA group received EA at "Baihui" (GV20), "Dazhui" (GV14), and bilateral "Shenshu"(BL23) for 30 min, 6 days a week for a total of 4 weeks. Morris water maze test was used to assess the cognitive function of rats. Evans blue staining was used to detect the BBB permeability, transmission electron microscopy and ELISA were used to detect the ultrastructure of BBB and the contents of hippocampal IL-1ß and IL-18, respectively. RESULTS: Following modeling, compared with the sham operation group, the mean escape latency of model group was significantly prolonged (P<0.01), the times of crossing the platform were significantly decreased (P<0.01), the content of Evans blue, and the contents of IL-1ß and IL-18 in hippocampus were increased (P<0.01). After the intervention, comparison between the model and EA groups showed that the average escape latency of rats in EA group was significantly shortened (P<0.01), the times of crossing the platform were increased (P<0.05), the content of Evans blue, and the contents of IL-1ß and IL-18 in hippocampus were significantly decreased (P<0.01). The ultrastructure of BBB was moderately damaged in the model group, which was evidenced by blurred endothelial cell membrane structure, obviously dropsical astrocyte foot process, and decreased tight junctions. The ultrastructure of BBB was slightly damaged and astrocyte foot had no obvious edema in the EA group. CONCLUSION: EA can significantly improve the learning and memory ability of VD rats and improve the BBB permeability, which may be related to its effect in inhibiting the expression of IL-1ß and IL-18 in the hippocampus.

Gut microbiota mediates the inhibition of lymphopoiesis in dietary-restricted mice by suppressing glycolysis.

Dietary restriction (DR) is one of the most robust interventions shown to extend health-span and remains on the forefront of anti-aging intervention studies, though conflicting results have been shown on its effect on lifespan both in rodents and primates. The severe inhibitory effects on the lymphoid lineage by DR remains one of its major negative downsides which reduces its overall beneficial effects on organismal health. Yet, the underlying mechanism of how DR suppresses the lymphoid system remains to be explored. Here, we show that antibiotic ablation of gut microbiota significantly rescued the inhibition of lymphopoiesis by DR. Interestingly, glycolysis in lymphocytes was significantly down-regulated in DR mice and pharmacological inhibition of glycolysis reverted this rescue effect of lymphopoiesis in DR mice with ablated gut microbiota. Furthermore, DR remarkably reconstructed gut microbiota with a significant increase in butyrate-producing bacterial taxa and in expression of But, a key gene involved in butyrate synthesis. Moreover, supplemental butyrate feeding in AL mice suppressed glycolysis in lymphoid cells and mimicked the inhibition of lymphopoiesis in AL mice. Together, our study reveals that gut microbiota mediates the inhibition on lymphopoiesis via down-regulation of glycolysis under DR conditions, which is associated with increased butyrate-synthesis. Our study uncovered a candidate that could potentially be targeted for ameliorating the negative effects of DR on lymphopoiesis, and therefore may have important implications for the wider application of DR and promoting healthy aging.

[Effects of electroacupuncture on ROS-NLRP3 inflammatory pathway and autophagy related proteins in hippocampus of vascular dementia rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on learning-memory ability, ultrastructural changes of hippocampal CA1 neurons, reactive oxygen species (ROS) level, Nod-like receptor protein 3 (NLRP3) and auto-phagy-related proteins expression in the hippocampus of vascular dementia (VD) rats, so as to reveal its partial mechanisms in treating VD. METHODS: Male SD rats were randomly divided into sham operation, model, and EA groups (n=10 rats in each group). The VD model was established by permanent ligation of bilateral common carotid arteries. Rats of the EA group were treated with EA at "Baihui" (GV20), "Dazhui" (GV14) and bilateral "Shenshu" (BL23) for 30 min, once a day for 4 weeks. Morris water maze was used to evaluate the learning and memory ability of rats before modeling, 4 weeks after modeling and after intervention. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes of hippocampal CA1 neurons. The level of ROS in hippocampus was detected by DCFH-DA fluorescence probe. The expressions of NLRP3, autophagy-related protein Beclin1 and microtubule-associated protein 1 light chain 3 (LC3) were measured by Western blot. RESULTS: In comparison with the sham operation group, the average escape latency of rats in the model group was prolonged (P<0.01), and the times of crossing the original platform were reduced (P<0.05), the level of ROS, the expression levels of LC3-Ⅱ/LC3-Ⅰ ratio, Beclin1 and NLRP3 proteins in hippocampus were increased (P<0.01, P<0.05) in the model group. After EA intervention, the average escape latency of rats was significantly shortened (P<0.01), and the times of crossing the original platform were increased (P<0.05), the level of ROS, the expression levels of LC3-Ⅱ/LC3-Ⅰ ratio, Beclin1 and NLRP3 proteins in hippocampus were decreased (P<0.01, P<0.05) in the EA group compared with those of the model group. Outcomes of TEM showed that CA1 neurons in the hippocampus were damaged, chromatin aggregation, mitochondria pyknosis, cristae structure disorder, rough endoplasmic reticulum expanded and degranulated, the number of free ribosomes decreased, and autophagy could be seen in the model group, which were milder in the EA group. CONCLUSION: EA at GV20, GV14 and BL23 can improve the learning and memory abilities of VD rats, alleviate the ultrastructural damage of neurons in hippocampal CA1 area, and repair the damaged neurons. The mechanism may be related to the reduction of ROS level, LC3-Ⅱ/LC3-Ⅰ ratio, NLRP3 and Beclin1 protein expression, the decrease of neuronal autophagy, inhibition of activation of NLRP3 inflammasome and alleviation of central inflammatory response.

[Effect of electroacupuncture on gut microbiota and serum IL-1ß and IL-18 in rats with vascular dementia based on principle of "curing brain disorders by treating intestines"].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Baihui"(GV20), "Dazhui"(GV14), "Shenshu" (BL23)and "Zusanli"(ST36) on the intestinal flora and serum interleukin (IL)-1ß and IL-18 contents in vascular dementia (VD) rats. METHODS: SD rats were randomized into sham operation, VD model, GV20+GV14+BL23 (EA-basic acupoints), and EA-basic acupoints+ST36 and EA-basic acupoints+probiotics groups (n=10 in each group). EA (10 Hz/50 Hz) was conducted for 30 min, once daily for 4 consecutive weeks. Rats of the EA-basic acupoints+probiotics received gavage of probiotics (2 mL/d containing 2.0×109 CFU of live bifidobacterium), once a day for 4 weeks, and those of the EA-basic acupoints and EA-basic acupoints+ST36 groups received gavage of the same dose of normal saline. The Morris water maze test was used to evalua-te the rats' lear-ning and memory ability before and after the treatment. The serum IL-1ß and IL-18 levels were determined by ELISA, and the histopathological changes of the intestinal mucosa were observed by H.E. staining. The ultrastructural changes of hippocampal neurons were observed by using transmission electron microscopy and 16S rDNA sequencing technique was used to analyze the composition of intestinal microbiome. RESULTS: Compared with the sham operation group, the escape latency, serum levels of IL-1ß and IL-18, as well as the relative abundance of harmful bacteria (including Catabacter, obinsoniella and Desulfovibrio) in the intestine were significantly increased (P<0.01). In comparison with the model group, the escape latency, serum levels of IL-1ß and IL-18 in the three treatment groups, and the relative abundance of harmful bacteria (such as the Catabacter, Robinsoniella and Desulfovibrio) in the EA-basic acupoints+ST36 group were down-regulated obviously(P<0.05,P<0.01), and the relative abundance of Clostridiales-unclassified in both EA-basic acupoints+probiotics and EA-basic acupoints+ST36 groups was significantly up-regulated (P<0.05). The effects of EA-basic acupoints+ST36 and EA-ba-sic acupoints+probiotics were significantly superior to that of EA-basic acupoints in down-regulating IL-18 content (P<0.05). H.E. staining showed atrophy of the whole mucosal layer, loss of goblet cells, destruction of glands, infiltration of a large number of inflammatory cells, and transmission microscope displayed fuzziness of the nucleus membrane boundary, cystic dilation of the rough endoplasmic reticulum with unclear structure swelling of the mitochondria, and disordered arrangement or dissolution of the inner cristae in the model group, which was relatively milder in the EA-basic acupoints+ST36 and EA-basic acupoints+probiotics groups. CONCLUSION: EA of GV20+GV14+BL23+ ST36 can improve the cognitive dysfunction of VD model rats, which may be related to its function in regulating the imbalance of intestinal microbiota, thereby inhibiting the peripheral inflammatory factor.

[Acupoint selection rules of neurogenic dysphagia treated with acupuncture and moxibustion in ancient times].

Acupoint selection rules of neurogenic dysphagia treated with acupuncture and moxibustion from pre-Qin to late Qing Dynasty in Chinese Medical Classics were analyzed based on data mining. The literature regarding acupuncture and moxibustion for neurogenic dysphagia was searched and screened according to the inclusion and exclusion criteria in Chinese Medical Classics (5th Edition), the prescriptions were extracted according to the principle of acupoint extraction.The SPSS 21.0 and Clementine 12.0 were used to perform the cluster analysis and association rule analysis.A total of 191 acupuncture and moxibustion prescriptions were screened and extracted，including 45 acupoints. The top 5 acupoints of acupuncture and moxibustion for neurogenic dysphagia in frequency were Jiache (ST 6), Dicang (ST 4), Lieque (LU 7), Lianquan (CV 23), Shuigou (GV 26). The most involved meridians were the stomach meridian, the governor vessel and the conception vessel. The main acupoints were distributed in the scalp face neck and upper limbs. The most frequently used specific acupoints was crossing points,next was eight confluence points. There were 11 acupoint combinations with strong association according to the association rule analysis, and the top one acupoint combination was Hegu (LI 4)-Jiache (ST 6). There were 9 acupoint cluster groups according to the cluster analysis. Hegu (LI 4), Jiache (ST 6), Dicang (ST 4), Shuigou (GV 26) and Chengjiang (CV 24) were core acupoints for neurogenic dysphagia treated with acupuncture and moxibustion in ancient times, besides，selecting proximal and distal acupoints and selecting acupoints according to symptoms were emphasized.

Short UV-B Exposure Stimulated Enzymatic and Nonenzymatic Antioxidants and Reduced Oxidative Stress of Cold-Stored Mangoes.

The effects of UV-B irradiation on reactive oxygen species (ROS) levels, antioxidant compound contents, antioxidative enzyme activities, and oxidative damage of cold-stored mangoes were examined. Superoxide anion production rate, hydrogen peroxide concentration, ion leakage level and malondialdehyde content of the cold-stored fruit preradiated with 5 KJ m(-2) UV-B for 4 h were significantly decreased as compared with control fruit. The activities of ROS generating enzymes remained unchanged in UV-B-irradiated mangoes as compared to the control, but superoxide dismutase and catalase activities, ascorbate and polyphenol contents and antioxidant capacities of the cold-stored mangoes were significantly enhanced by UV-B. The UV-B-enhanced antioxidant compounds and antioxidative enzymes were highly correlated with the reduced-ROS levels in UV-B-irradiated mangoes. The data indicated that a short UV-B exposure reduced oxidative stress and alleviated oxidative damage of the cold-stored mangoes by triggering both enzymatic and nonenzymatic antioxidant systems although ROS generation in the fruit was not affected.

Genome sequence of Paenibacillus sp. strain Aloe-11, an endophytic bacterium with broad antimicrobial activity and intestinal colonization ability.

Paenibacillus sp. strain Aloe-11, a Gram-positive, spore-forming, facultatively anaerobic bacterium isolated from the root of Aloe chinensis in the southwest region of China, has excellent antibiotic activity and intestine colonization ability. Here, we present the 5.8-Mb draft genome sequence of Paenibacillus sp. strain Aloe-11.