Phytochemical Modulation of Apoptosis and Autophagy: Strategies to Overcome Chemoresistance in Leukemic Stem Cells in the Bone Marrow Microenvironment.

Advances in scientific research and targeted treatment regimes have improved survival rates for many cancers over the past few decades. However, for some types of leukemia, including acute lymphoblastic and acute myeloid leukemia, mortality rates have continued to rise, with chemoresistance in leukemic stem cells (LSCs) being a major contributing factor. Most cancer drug therapies act by inducing apoptosis in dividing cells but are ineffective in targeting quiescent LSCs. Niches in the bone marrow, known as leukemic niches, behave as "sanctuaries" where LSCs acquire drug resistance. This review explores the role of the bone marrow environment in the maintenance of LSCs and its contribution to chemoresistance and considers current research on the potential use of phytochemicals to overcome chemoresistance through the modulation of signaling pathways involved in the survival and death of leukemic clonal cells and/or leukemic stem cells. Phytochemicals from traditional Chinese medicine, namely baicalein, chrysin, wogonin (constituents of Scutellaria baicalensis; huáng qín; ), curcumin (a constituent of Curcuma longa, jiang huáng, ), and resveratrol (a constituent of Polygonum cuspidatum; hu zhàng, ) have been shown to induce apoptosis in leukemic cell lines, with curcumin and resveratrol also causing cell death via the induction of autophagy (a nonapoptotic pathway). In order to be effective in eliminating LSCs, it is important to target signaling pathways (such as Wnt/ß-catenin, Notch, and Hedgehog). Resveratrol has been reported to induce apoptosis in leukemic cells through the inhibition of the Notch and Sonic hedgehog signaling pathways, therefore showing potential to affect LSCs. While these findings are of interest, there is a lack of reported research on the modulatory effect of phytochemicals on the autophagic cell death pathway in leukemia, and on the signaling pathways involved in the maintenance of LSCs, highlighting the need for further work in these areas.

Effects of laser vs ultrasound on bone healing after distraction osteogenesis: A histomorphometric analysis.

OBJECTIVE: To assess the effects of low-level laser irradiation vs ultrasound irradiation on bone healing after distraction osteogenesis. MATERIALS AND METHODS: Distraction osteogenesis was performed with rapid maxillary expansion devices (Hyrax-Morelli, Sorocaba, São Paulo Brazil) in 24 rabbits (Oryctolagus cuniculus). After a 2-day latency period, the distraction devices were activated for 10 days at a rate of 1 mm/d. Four groups of six animals were treated as follows: (1) control, (2) laser irradiation on the right side, (3) ultrasound irradiation on the right side, and (4) laser irradiation on the right side and ultrasound on the left side. Histomorphometric analysis was used to assess the bone healing area. Analysis of variance was used to perform the statistical analyses. RESULTS: The influence of low-intensity laser associated with ultrasound irradiation on bone healing was statistically significant. The analyses showed the greatest amount of bone healing in the jaws of animals in group 4, which received treatment with both ultrasound and laser. CONCLUSION: This study concluded that bone healing is accelerated with the application of laser irradiation. The greatest effects were observed with combined ultrasound and laser treatment.

[Effect of sulfated polysaccharides from brown seaweed Laminaria japonica on the morfology of lymfoid organs and functional characteristics of immunocompetent cells].

The effect of sulfated polysaccharide fucoidan from the brown alga Laminaria japonica on morphological characteristics of mouse lymphoid organs, subpopulations of spleen mononuclear leukocytes, cytokine production and cytotoxic activity of splenocytes has been investigated. Fucoidan promoted activation and proliferation of lymphoid hematopoietic cells in primary and secondary immunogenesis bodies, increased expression of markers CD19, NK, NKT, CD25, MHC II, TCR, TLR2 and TLR4, the cytotoxic activity of splenocytes and production of immunoregulatory and proinflammatory cytokines (IL- 2, IL-12, IFN-g, TNF-a, IL-6). This suggests activation of effector mechanisms of innate immunity and adaptive immune responses via the Th-1 type.

Effect of additional boron on tibias of African ostrich chicks.

The aim of the present study was to find out the effects of boron on ostrich chicks fed with 0 mg/l, 100 mg/l, 200 mg/l, and 400 mg/l of additional boron in water. We measured bone mineral density (BMD), perimeter, length, weight, ash content of ostrich tibias, thickness of cortical bone, and diameter of the marrow cavity. We also analyzed the apoptosis status of paraffin sections using a TUNEL kit and examined serum levels of leptin and estradiol (E(2)). The results were dramatic. Compared with the control group, group C had a very high BMD. The serum levels of leptin in groups C and D were significantly higher than control values, and the levels of E(2) fluctuated. The perimeter, length, weight, and ash content of ostrich tibias all increased significantly with increasing dosage of boron. The cross-section analysis revealed that the bone marrow cavity shifted closer to one side in group D, which was observed on a macro-scale. This shift may be related to the toxicity of excessive boron, as indicated by the apoptosis status. According to the present data, additional boron was helpful for ostrich chick bone development, and 200 mg/l supplement boron in the drinking water appeared to be the most beneficial.

Citologia de medula óssea das primeiras seis semanas de vida de bovinos da raça Holandesa / Cytology of the bone marrow of the first six weeks of life of Holstein cattle

The possible changes in the bone marrow associated with hematological changes in peripheral blood during the first six weeks of life in cattle were evaluated. To this purpose, blood samples were evaluated at 2, 4, 7, 10, 14, 21, 28, 35, and 42 days of life, and cytologic examination of bone marrow at 2, 7, 21, and 42 days of life in 10 Holstein calves. The bone marrow examination showed, in different times, myeloid:erythroid ratio from 0.60 to 0.69. The erythroid lineage distribution remained pyramidal, with concentration of precursor cells above the initial reference values for adult cattle. Proliferation pool of myeloid lineage also remained above the reference range, with decreases of concentrations in the third and sixth weeks. In the lymphoid lineage, the concentration of lymphocytes showed a decrease in the first three weeks, with a tendency to rise in the sixth week.

Docosahexaenoic acid supplementation-increased oxidative damage in bone marrow DNA in aged rats and its relation to antioxidant vitamins.

We compared the influence of docosahexaenoic acid (DHA) supplementation on oxidative DNA damage in bone marrow between young and aged rats. As a marker of oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OHdG) in DNA was analyzed. Young (5-week-old) and aged (100-week-old) female Wistar rats were given DHA (300mg/kg body weight/day) or vehicle (control) orally for 12 weeks. The 8-OHdG in the bone marrow in the aged DHA group was significantly higher than that in the other groups. Vitamin E concentrations, however, did not differ among the groups regardless of the DHA supplementation. Vitamin C (ascorbic acid) concentrations in the aged control group were approximately 1/2 those in the young control group. The concentrations of vitamin C tended to be higher in the young DHA group and lower in the aged DHA group when compared to their respective control groups. Changes in the concentrations of vitamin C and vitamin E in plasma were similar to those in the bone marrow. The activity of hepatic l-gulono- gamma -lactone oxidase, an enzyme responsible for vitamin C synthesis, corresponded well to the concentrations of vitamin C in the bone marrow and the plasma. These results suggest that in aged rats, but not young rats, excess supplementation of DHA induces oxidative DNA damage in bone marrow and that the decrease in vitamin C synthesis in aged rats is involved in the mechanisms of DNA damage.

[Doctor of medicine Awit Reniger (1853-1907) and his doctorate dissertation]. / Awit Reniger (1853-1907) i jego rozprawa na stopien doktora medycyny.

The author announced main details of Awit Reniger's life, main thesis and conclusions of his doctorate dissertation. Doctor's Thesis concerning: Pathological changes in the anatomy of marrow in cases of the phosphorus intoxication. This dissertation is not reported in S. Konopka's: Polish medical bibliography of the nineteenth century (1801-1900).

[Ultra-small superparamagnetic iron oxide particles: the signal behavior and relaxation times of the bone marrow after repeated i.v. application in the pig model at 1.5 tesla]. / Ultrakleine superparamagnetische Eisenoxidpartikel: Signalverhalten und Relaxationszeiten des Knochenmarks nach wiederholter i.v. Applikation im Schweinemodell bei 1,5 Tesla.

PURPOSE: Evaluation of the influence of an iron-containing MR contrast agent on the signal behaviour and the relaxation time of the bone marrow at 1.5 tesla after repeated doses. ANIMALS AND METHODS: 14 pigs received i.v. on days 1, 9, and 15 ultra-small (core diameter 6-8 nm) superparamagnetic iron oxide particles at doses of 20 (low dose = LD) or 200 mumol/kg body weight (high dose = HD). RESULTS: Following the first administration a dose-independent reduction in the bone-marrow signal intensity in the T2-weighted gradient-echo sequence (FFE) was observed together with a reduction in the T1 and T2 relaxation times. Following the second application there were no further signal-reductions in the HD-group; in contrast, there was a signal reduction in the LD-group, made possible by a signal recovery in the meantime. On the other hand, the relaxation times T1 and T2 were shortened after each administration of contrast medium. CONCLUSION: Nano-SIPS result at both doses in a signal reduction in the bone marrow. Only in the LD-group may repeated examinations with new contrast agent offer diagnostically sufficient images. Relaxometry shows a shortening of T1 as well as T2. This effect could be summed up after repeated doses. Almost no iron remained in the medullary space three weeks after i.v. administration of the contrast agent, which suggests mobilization and metabolization.

Communication of the intracranial space with sphenoid bone marrow in mice.

Tritiated thymidine and Ehrlich ascites tumour cells were injected intrathecally in adult Balb/c mice. Thymidine penetrated easily into the sphenoid bone marrow, where it labelled numerous leukocytes. The microvessel wall constituted a partly penetrable barrier against the infiltration of Ehrlich ascites tumour cells from arachnoid space into the bone marrow. A possible physiological role of the drainage of substances from the brain into the bone marrow is discussed.

Dietary boron modified the effects of magnesium and molybdenum on mineral metabolism in the cholecalciferol-deficient chick.

The metabolic effects of dietary boron, magnesium, and molybdenum on mineral metabolism in the cholecalciferol-deficient chick, with emphasis on growth cartilage histology, were studied. One-day-old cockerel chicks were assigned to groups in a fully-crossed, three factor, 2 x 2 x 2 design. The basal diet was based on ground corn, high-protein casein, and corn oil and contained 125 IU cholecalciferol (inadequate), 0.465 mg B, 2.500 mg Mg, and 0.420 mg Mo/kg. The treatments were the supplementation of the basal diet with B at O or 3; Mg at 300 (inadequate) or 500 (adequate); and Mo at 0 or 20 mg/kg. At d 25, B depressed mortality, alleviated the cholecalciferol-deficiency induced distortion of the marrow sprouts (MS) of the proximal tibial epiphysial plate, and elevated the numbers of osteoclasts within the MS. Adequate Mg exacerbated the cholecalciferol-deficiency induced bone lesions. Mo widened the MS markedly. In Mg-deficient chicks, B elevated plasma Ca and Mg concentrations and growth, but inhibited initiation of cartilage calcification; B had the opposite effect in Mg-adequate chicks. An interaction among B, Mg, and Mo affected plasma uric acid and glucose concentrations. B may function to modify mineral metabolism in cholecalciferol deficiency, suppressing bone anabolism in concurrent Mg deficiency and bone catabolism in concurrent Mg adequacy.

A study of the reaction of human tissue to proplast.

The femoral stems of Thompson prostheses coated with a polytetrafluoroethylene/carbon fiber composite (proplast) were studied using conventional histological examination, scanning electron microscopy and electron probe microanalysis in "successful" firm implants and in a "loose" clinically unsuccessful implant. Ingrowth was found throughout the coatings of the successful prostheses. In the most firmly fixed prosthesis the ingrowth consisted of fibrous tissue with abundant giant cells; however, no bone ingrowth was detected. There was less composite pore infilling in the unsuccessful implant. From both clinical, radiological and the studies described above, it is concluded that fibrous tissue ingrowth was a secondary stabilizing phenomenon in the proplast-coated prostheses studied.