The microbiome, which has been defined as ‘the ecological community of commensal, symbiotic and pathogenic microorganisms that share our body space, may be distinguished from the microbiota as it includes the collective genomes. An increasing level of evidence reveals that the human microbiome plays a major role in health. For this reason, it is often referred to as the ‘forgotten organ.’ All surfaces of the human body that are exposed to the environment are colonized, including skin, respiratory system, urogenital tract and gastrointestinal (GI) tract, totaling at least 100 trillion microbial cells. The known roles of the GI microbiome include metabolic functions, synthesis functions, and immune roles. Recent studies indicate that the human gut microbiome plays a significant role in health and disease. Dysbiosis, defined as a pathological imbalance in a microbial community, is becoming increasingly appreciated as a ‘central environmental factor’ that is both associated with complex phenotypes and affected by host genetics, diet, and antibiotic use. More recently, a link has been established between the dysmetabolism of bile acids (BAs) in the gut and the gut-liver axis, and this relationship with the microbiome has been highlighted. This review summarizes the microbiome of the hepatobiliary system and how microbiome is related to diseases of the liver and biliary tract.
Bile Acids and Salts ; Biliary Tract ; Biota ; Colon ; Diet ; Dysbiosis ; Gallbladder ; Gastrointestinal Microbiome ; Genetics ; Genome ; Human Body ; Humans ; Liver ; Microbiota* ; Pancreas ; Phenotype ; Respiratory System ; Skin

BACKGROUND: Parkinson disease (PD) is caused by selective cell death of dopaminergic neurons in the substantia nigra. An early onset form of PD, autosomal recessive juvenile parkinsonism has been associated with a mutation in the parkin gene. The function of parkin is known to remove misfolding proteins and protect cell death. We aimed to investigate the role of parkin against oxidative stress in neuronal cells. METHODS: Parkin knockout embryonic stem cells (PKO ES cells) were differentiated into neurons by adherent monolayer culture method. Oxidative stress was induced by the treatment of 1-methyl-4-phenylpyridinium (MPP+) in neurons derived from wild type and PKO ES cells, and cell viability was examined by MTT assay. After exposure to MPP+, Tuj1-positive cell population was compared between PKO and wild type cells by fluorescence activated cell sorter (FACS) analysis. The activated caspase3 protein level was also measured by Western blot analysis, FACS and immunocytochemistry. RESULTS: There was no difference in the efficiency of neuronal differentiation between wild type and PKO ES cells. After exposure to MPP+, no significant differences were found in cell viability and Tuj1-positive cell population between the two groups determined by MTT assay and FACS analysis, respectively. The activated caspase3 protein levels examined by Western blot analysis, FACS and immunocytochemistry were not changed in PKO cells compared with those of wild type cells after MPP+ treatment. CONCLUSION: These results suggest that PKO neuronal cells including dopaminergic neurons are not sensitive to caspase3-dependent cell death pathway during the response against MPP+-induced oxidative stress.
1-Methyl-4-phenylpyridinium ; Blotting, Western ; Cell Death ; Cell Survival ; Dopaminergic Neurons ; Embryonic Stem Cells ; Fluorescence ; Immunohistochemistry ; Neurons ; Oxidative Stress* ; Parkinson Disease ; Parkinsonian Disorders ; Substantia Nigra

The liver is the largest organ in the body; it has a complex architecture, wide range of functions and unique regenerative capacity. The growing incidence of liver diseases worldwide requires increased numbers of liver transplant and leads to an ongoing shortage of donor livers. To meet the huge demand, various alternative approaches are being investigated including, hepatic cell transplantation, artificial devices and bioprinting of the organ itself. Adult hepatocytes are the preferred cell sources, but they have limited availability, are difficult to isolate, propagate poor and undergo rapid functional deterioration in vitro. There have been efforts to overcome these drawbacks; by improving culture condition for hepatocytes, providing adequate extracellular matrix, co-culturing with extra-parenchymal cells and identifying other cell sources. Differentiation of human stem cells to hepatocytes has become a major interest in the field of stem cell research and has progressed greatly. At the same time, use of decellularized organ matrices and 3 D printing are emerging cutting-edge technologies for tissue engineering, opening up new paths for liver regenerative medicine. This review provides a compact summary of the issues, and the locations of liver support systems and tissue engineering, with an emphasis on reproducible and useful sources of hepatocytes including various candidates formed by differentiation from stem cells.
Adult ; Bioprinting ; Extracellular Matrix ; Hepatocytes ; Humans ; Incidence ; Liver Diseases ; Liver Transplantation* ; Liver* ; Liver, Artificial ; Regenerative Medicine ; Stem Cell Research ; Stem Cells ; Tissue Donors ; Tissue Engineering*

Objective: : To investigate the clinical efficacy and safety of the controlled distraction-compression technique using an expandable titanium cage (ETC) in posttraumatic kyphosis (PTK). Methods: : We retrospectively studied and collected data on 20 patients with PTK. From January 2014 to December 2017, the controlled distraction-compression technique using ETC was consecutively performed in 20 patients with PTK of the thoracolumbar zone (range, 36–82 years). Among them, nine were males and 11 were females and the mean age was 61.5 years. The patients were followed regularly at 1, 3, 6, and 12 months, and the last follow-up was more than 2 years after surgery. Results: : The mean follow-up period was 27.3±7.3 months (range, 14–48). The average operation time was 286.8±33.1 minutes (range, 225–365). The preoperative regional kyphotic angle (RKA) ranged from 35.6° to 70.6° with an average of 47.5°±8.1°. The immediate postoperative mean RKA was 5.9°±3.8° (86.2% correction rate, p=0.000), and at the last follow-up more than 2 years later, the mean RKA was 9.2°±4.9° (80.2% correction rate, p=0.000). The preoperative mean thoracolumbar kyphosis was 49.1°±9.2° and was corrected to an average of 8.8°±5.3° immediately after surgery (p=0.000). At the last follow-up, a correction of 11.9°±6.3° was obtained (p=0.000). The preoperative mean back visual analog scale (VAS) score was 7.9±0.8 and at the last follow-up, the VAS score was improved to a mean of 2.3±1.0 with a 70.9% correction rate (p=0.000). The preoperative mean Oswestry disability index (ODI) score was 32.3±6.9 (64.6%) and the last follow-up ODI score was improved to a mean of 6.85±2.9 (3.7%) with a 78.8% correction rate (p=0.000). The overall complication was 15%, with two of distal junctional fractures and one of proximal junctional kyphosis and screw loosening. However, there were no complications directly related to the operation. Conclusion : PVCR through the controlled distraction-compression technique using ETC showed safe and good results in terms of complications, and clinical and radiologic outcomes in PTK. However, to further evaluate the efficacy of this surgical procedure, more patients need long-term follow-up and there is a need to apply it to other diseases.

Melorheostosis is a rare type of sclerosing bone dysplasia with an incidence of approximately 0.9 per million individuals. This disease predominantly affects the appendicular skeleton, with rare involvement of the axial skeleton. Patients with spinal melorheostosis may present with symptoms such as scoliosis, stiffness, back pain, progressive myelopathy, radiculopathy, and vertebrobasilar insufficiency. Surgical management for spinal melorheostosis has been reported, but it remains exceedingly rare. Here, we present the case of a 67-year-old woman with incidental findings on thoracic vertebral imaging from a preoperative chest computed tomography scan performed for shoulder surgery. The patient had experienced gait disturbances and mild, motion-related back pain for approximately 2 to 3 years, along with a recent symptom of mild tingling sensations in both feet. A diagnosis of spinal melorheostosis was considered based on the characteristic imaging findings. In this case, rather than prioritizing the severity of the current symptoms, we focused on the location and extent of osteosclerotic lesions, which are directly associated with the potential development of neurological complications. Therefore, we opted for surgical treatment involving decompression and screw fixation. The patient’s symptoms were relieved without significant surgical complications over a 1-year follow-up period.

Melorheostosis is a rare type of sclerosing bone dysplasia with an incidence of approximately 0.9 per million individuals. This disease predominantly affects the appendicular skeleton, with rare involvement of the axial skeleton. Patients with spinal melorheostosis may present with symptoms such as scoliosis, stiffness, back pain, progressive myelopathy, radiculopathy, and vertebrobasilar insufficiency. Surgical management for spinal melorheostosis has been reported, but it remains exceedingly rare. Here, we present the case of a 67-year-old woman with incidental findings on thoracic vertebral imaging from a preoperative chest computed tomography scan performed for shoulder surgery. The patient had experienced gait disturbances and mild, motion-related back pain for approximately 2 to 3 years, along with a recent symptom of mild tingling sensations in both feet. A diagnosis of spinal melorheostosis was considered based on the characteristic imaging findings. In this case, rather than prioritizing the severity of the current symptoms, we focused on the location and extent of osteosclerotic lesions, which are directly associated with the potential development of neurological complications. Therefore, we opted for surgical treatment involving decompression and screw fixation. The patient’s symptoms were relieved without significant surgical complications over a 1-year follow-up period.

Melorheostosis is a rare type of sclerosing bone dysplasia with an incidence of approximately 0.9 per million individuals. This disease predominantly affects the appendicular skeleton, with rare involvement of the axial skeleton. Patients with spinal melorheostosis may present with symptoms such as scoliosis, stiffness, back pain, progressive myelopathy, radiculopathy, and vertebrobasilar insufficiency. Surgical management for spinal melorheostosis has been reported, but it remains exceedingly rare. Here, we present the case of a 67-year-old woman with incidental findings on thoracic vertebral imaging from a preoperative chest computed tomography scan performed for shoulder surgery. The patient had experienced gait disturbances and mild, motion-related back pain for approximately 2 to 3 years, along with a recent symptom of mild tingling sensations in both feet. A diagnosis of spinal melorheostosis was considered based on the characteristic imaging findings. In this case, rather than prioritizing the severity of the current symptoms, we focused on the location and extent of osteosclerotic lesions, which are directly associated with the potential development of neurological complications. Therefore, we opted for surgical treatment involving decompression and screw fixation. The patient’s symptoms were relieved without significant surgical complications over a 1-year follow-up period.

Melorheostosis is a rare type of sclerosing bone dysplasia with an incidence of approximately 0.9 per million individuals. This disease predominantly affects the appendicular skeleton, with rare involvement of the axial skeleton. Patients with spinal melorheostosis may present with symptoms such as scoliosis, stiffness, back pain, progressive myelopathy, radiculopathy, and vertebrobasilar insufficiency. Surgical management for spinal melorheostosis has been reported, but it remains exceedingly rare. Here, we present the case of a 67-year-old woman with incidental findings on thoracic vertebral imaging from a preoperative chest computed tomography scan performed for shoulder surgery. The patient had experienced gait disturbances and mild, motion-related back pain for approximately 2 to 3 years, along with a recent symptom of mild tingling sensations in both feet. A diagnosis of spinal melorheostosis was considered based on the characteristic imaging findings. In this case, rather than prioritizing the severity of the current symptoms, we focused on the location and extent of osteosclerotic lesions, which are directly associated with the potential development of neurological complications. Therefore, we opted for surgical treatment involving decompression and screw fixation. The patient’s symptoms were relieved without significant surgical complications over a 1-year follow-up period.

OBJECTIVE: This study was to identify small inhibitory RNAs (siRNAs) that are effective in inhibiting growth of cervical cancer cell lines harboring human papilloma virus (HPV) and to examine how siRNAs interact with interferon beta (IFN-beta) and thimerosal. METHODS: The HPV18-positive HeLa and C-4I cell lines were used. Four types of siRNAs were designed according to their target (both E6 and E7 vs. E6 only) and sizes (21- vs. 27-nucleotides); Ex-18E6/21, Ex-18E6/27, Sp-18E6/21, and Sp-18E6/27. Each siRNA-transfected cells were cultured with or without IFN-b and thimerosal and their viability was measured. RESULTS: The viabilities of HPV18-positive tumor cells were reduced by 21- and 27-nucleotide siRNAs in proportion to the siRNA concentrations. Of the two types of siRNAs, the 27-nucleotide siRNA constructs showed greater inhibitory efficacy. Sp-18E6 siRNAs, which selectively downregulates E6 protein only, were more effective than the E6- and E7-targeting Ex-18E6 siRNAs. siRNAs and IFN-beta showed the synergistic effect to inhibit HeLa cell survival and the effect was proportional to both siRNA and IFN-beta concentrations. Thimerosal in the presence of siRNA exerted a dose-dependent inhibition of C-4I cell survival. Finally, co-treatment with siRNA, IFN-beta, and thimerosal induced the most profound decrease in the viability of both cell lines. CONCLUSION: Long (27-nucleotides) siRNAs targeting E6-E7 mRNAs effectively reduce the viability of HPV18-positive cervical cancer cells and show the synergistic effect in combination with IFN-b and thimerosal. It is necessary to find the rational design of siRNAs and effective co-factors to eradicate particular cervical cancer.
Cell Line ; Cell Survival ; HeLa Cells ; Humans ; Interferon-beta ; Papilloma* ; RNA* ; RNA, Messenger ; RNA, Small Interfering ; Thimerosal ; Uterine Cervical Neoplasms*

We investigated effects of reblastatins on phenotypic changes in monocytes/macrophages induced by 27-hydroxycholesterol (27OHChol). Treatment of THP-1 monocytic cells with reblastatin derivatives, such as 17-demethoxy-reblastatin (17-DR), 18-dehydroxyl-17-demethoxyreblastatin (WK88-1), 18-hydroxyl-17-demethoxyreblastatin (WK88-2), and 18-hydroxyl-17-demethoxy-4,5-dehydroreblastatin (WK88-3), resulted in blockage of CCL2, CCL3, and CCL4 expression at the transcription and protein levels, which, in turn, impaired migration of monocytes/macrophages and Jurkat T cells expressing CCR5, and almost complete inhibition of transcription of M1 marker cytokines, like CXCL10, CXCL11, and TNF-α. Reblastatins also downregulated surface CD14 as well as soluble CD14 along with inhibition of LPS response and matrix metalloprotease-9 expression. Surface levels of mature dendritic cell (mDC)-specific markers, including CD80, CD83, CD88, CD197, and MHC class I and II molecules, were remarkably down-regulated, and 27OHChol-induced decrease of endocytic activity was recovered following treatment with 17-DR, WK88-1, WK88-2, and WK88-3. However, 15-hydroxyl-17-demethoxyreblastatin (DHQ3) did not affect the molecular or functional changes in monocytic cells induced by 27OHChol. Furthermore, surface levels of CD105, CD137, and CD166 were also down-regulated by 17-DR, WK88-1, WK88-2, and WK88-3, but not by DHQ3. Collectively, results of the current study indicate that, except DHQ3, reblastatins regulate the conversion and differentiation of monocytic cells to an immunostimulatory phenotype and mDCs, respectively, which suggests possible applications of reblastatins for immunomodulation in a milieu rich in oxygenated cholesterol molecules.