Calcifying Nanoparticles (Nanobacteria): An Additional Potential Factor for Urolithiasis in Space Flight Crews

Jones, Jeffrey A.; Çiftçioğlu, Neva; Schmid, Josef; Barr, Yael; Griffith, Donald P.

doi:10.1016/j.urology.2008.01.033

Cited by 19 publications

(14 citation statements)

References 12 publications

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“…NB have been proposed to be important in the pathogenesis of various human diseases, especially in association with a variety of pathological calcifications; notably, cholecystolithiasis; bladder, renal, and ureteral lithiasis; placental calcification; psammoma bodies of ovarian cancer; and arterial sclerosis. [13][14][15][16][17][18] However, the role of NB in cancer cell growth has not been reported so far. In the current study, we investigated the cytotoxic effects of NB and nanohydroxyapatites (nHAPs) against human MDA-MB-231 breast cancer cells and elucidated the mechanisms of action underlying this cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity and apoptosis induced by nanobacteria in human breast cancer cells

Zhang¹,

Liu²,

Xu³

et al. 2013

IJN

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Background The existing evidence that nanobacteria (NB) are closely associated with human disease is overwhelming. However, their potential toxicity against cancer cells has not yet been reported. The objective of this study was to investigate the cytotoxic effects of NB and nanohydroxyapatites (nHAPs) against human breast cancer cells and to elucidate the mechanisms of action underlying their cytotoxicity. Methodology/principal findings NB were isolated from calcified placental tissue, and nHAPs were artificially synthesized. The viability of the MDA-MB-231 human breast cancer cell line was tested by using the Kit-8 cell counting kit assay. Apoptosis was examined by transmission electron microscopy and flow cytometry. The endocytosis of NB and nHAPs by MDA-MB-231 cells was initially confirmed by microscopy. Although both NB and nHAPs significantly decreased MDA-MB-231 cell viability and increased the population of apoptotic cells, NB were more potent than nHAPs. After 72 hours, NB also caused ultrastructural changes typical of apoptosis, such as chromatin condensation, nuclear fragmentation, nuclear dissolution, mitochondrial swelling, and the formation of apoptotic bodies. Conclusion/significance In MDA-MB-231 human breast cancer cells, NB and nHAPs exerted cytotoxic effects that were associated with the induction of apoptosis. The effects exerted by NB were more potent than those induced by nHAPs. NB cytotoxicity probably emerged from toxic metabolites or protein components, rather than merely the hydroxyapatite shells. NB divided during culturing, and similar to cells undergoing binary fission, many NB particles were observed in culture by transmission electron microscopy, suggesting they are live microorganisms.

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Section: Introductionmentioning

confidence: 99%

Cytotoxicity and apoptosis induced by nanobacteria in human breast cancer cells

Zhang¹,

Liu²,

Xu³

et al. 2013

IJN

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“…These nanobacteria are implicated in many human diseases, including kidney and gallbladder stones, testicular microliths, chronic prostatitis, rheumatoid arthritis, dental pulp stones, salivary gland stones, ovarian cancer, and atherosclerosis. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Calcifying nanoparticles were found to be opportunistic pathogens in 5% of Finns and 8% of Chinese individuals 31 on blood testing. In addition, calcifying nanoparticle infections have also been observed in placental calcification and psammoma bodies.…”

Section: Introductionmentioning

confidence: 99%

Association between calcifying nanoparticles and placental calcification

Guo

Zhang²,

Lü³

et al. 2012

IJN

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Background:The purpose of this study was to examine the possible contribution of calcifying nanoparticles to the pathogenesis of placental calcification. Methods: Calcified placental tissues and distal tissue samples were collected from 36 confirmed placental calcification cases. In addition, 20 normal placental tissue samples were obtained as a control group. All the tissue samples were cultured using special nanobacterial culture methods. The cultured calcifying nanoparticles were examined by transmission electron microscopy (TEM), and their growth was monitored by optical density (OD) at a wavelength of 650 nm. 16S rRNA gene expression of the cultured calcifying nanoparticles was also isolated and sequenced. Results: Novel calcifying nanoparticles wrapped with electron-dense shells between 50 nm to 500 nm in diameter were observed in the extracellular matrix of calcified placental tissues. They were detected in placental villi and hydroxyapatite crystals, and contained "nucleic acidlike materials". After isolation and four weeks of culture, 28 of 36 calcified placental tissue samples showed white granular precipitates attached to the bottom of the culture tubes. OD 650 measurements indicated that the precipitates from the calcified placental tissues were able to grow in culture, whereas no such precipitates from the control tissues were observed. The 16S rRNA genes were isolated from the cultured calcifying nanoparticles and calcified placental tissues, and their gene sequencing results implied that calcifying nanoparticles were novel nanobacteria (GenBank JF823648). Conclusion: Our results suggest that these novel calcifying nanoparticles may play a role in placental calcification.

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“…Increasing number of reports has shown the role of NB in urologic diseases [10] and their occurrence in human renal pathologies such as polycystic kidney disease [5] and stone formations [11]. Researchers at NASA (National Aeronautics and Space Administration) have found that human NB multiply faster in a lowgravity environment, an observation deemed to be linked to the high risk of developing kidney stones for astronauts [12,13]. Kidney stone formation was reported to occur following injection of NB into rats [14,15].…”

Section: Introductionmentioning

confidence: 99%

Occurrence of Nanobacteria-Like Particles in Renal Stones of a Southern Brazilian Population

Simonetti¹,

Ros²,

David³

et al. 2012

OJU

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Purpose: Identifying the source of stone formation in recurrent stone formers has always been a big problem. Material and Methods: In this study kidney stones from 52 patients were submitted to direct examination by scanning electronic microscopy (SEM) after manual fracture and 27 calculi were cultured in Eagle’s Minimum Essential Medium (E-MEM) and Brain-Heart Infusion (BHI) for eight weeks at 37°C in 5% CO<sub>2</sub> atmosphere. Twenty-seven powdered and demineralized stones were suspended in sterile PBS, filtered through 0.22 m-pore-size sterile filters Millex (Millipore, Massachusetts, USA) and submitted to DNA extraction (Quiagen-Brazil). Platinum PCR SuperMIX (GIBCO-BRL), primers (Invitrogen), and Ultra Pure Water (Advanced Biotechnologies, Columbia, MD) were used for PCR (Polymerase Chain Reaction), which was generally conducted for 30 or 35 cycles with annealing of primers for 40 sec at 55°C and extension for 1 min at 72°C. Results: In 36 out 52 (69%) kidney stones it was detected the presence of biofilm coating the mineral surface of the stone when examined by SEM, consisting of coccoid particles, isolated or clustered, with diameter of 500 nm or less. Eleven out 27 (41%) kidney stone cultures produced white-colored sediment on the bottom of the tubes after eight-week incubation, revealing tiny structures similar to those observed directly by SEM. These structures were similar in size and morphology to spherical apatite particles previously observed in human kidney stones and named as nanobacteria (NB). No PCR products were observed in the samples. Conclusion: We found a strong correlation between renal stones and calcifying nanoparticles (CNP) in this study and these results open a new insight on this area to explore the etiology of stone formation. Whether NB/CNP are truly microorganisms or self-propagating mineral compounds is still controversial and its contribution, if any, in apatite nucleation and crystal growth remains uncertain

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Calcifying Nanoparticles (Nanobacteria): An Additional Potential Factor for Urolithiasis in Space Flight Crews

Cited by 19 publications

References 12 publications

Cytotoxicity and apoptosis induced by nanobacteria in human breast cancer cells

Cytotoxicity and apoptosis induced by nanobacteria in human breast cancer cells

Association between calcifying nanoparticles and placental calcification

Occurrence of Nanobacteria-Like Particles in Renal Stones of a Southern Brazilian Population

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