scholarly journals Metabolic switching and cell wall remodelling of Mycobacterium tuberculosis during bone tuberculosis

2022 ◽  
Author(s):  
Khushpreet Kaur ◽  
Sumedha Sharma ◽  
Sudhanshu Abhishek ◽  
Prabhdeep Kaur ◽  
Uttam C. Saini ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Bone Destruction ◽  
Human Bone ◽  
Survival Strategies ◽  
Bone Lesions ◽  
P Value ◽  
Osteoblast Cell ◽  
Osteoblast Cell Line ◽  
Bone Tuberculosis

Bone tuberculosis is widely characterized by irreversible bone destruction caused by Mycobacterium tuberculosis . Mycobacterium has the ability to adapt to various environmental stresses by altering its transcriptome in order to establish infection in the host. Thus, it is of critical importance to understand the transcriptional profile of M. tuberculosis during infection in the bone environment compared to axenic cultures of exponentially growing M.tb. In the current study, we characterized the in vivo transcriptome of M. tuberculosis within abscesses or necrotic specimens obtained from patients with bone TB using whole genome microarrays in order to gain insight into the M. tuberculosis adaptive response within this host microenvironment. A total of 914 mycobacterial genes were found to be significantly over-expressed and 1688 were repressed (fold change>2; p-value ≤ 0.05) in human bone TB specimens. Overall, the mycobacteria displayed a hypometabolic state with significant (p ≤ 0.05) downregulation of major pathways involved in translational machinery, cellular and protein metabolism and response to hypoxia. However, significant enrichment (p ≤ 0.05) of amino-sugar metabolic processes, membrane glycolipid biosynthesis, amino acid biosynthesis (serine, glycine, arginine and cysteine) and accumulation of mycolyl-arabinogalactan-peptidoglycan complex suggests possible mycobacterial survival strategies within the bone lesions by strengthening its cell wall and cellular integrity. Data were also screened for M.tb virulence proteins using Virulent-Pred and VICM-Pred tools, which revealed five genes (Rv1046c, Rv1230c, DppD, PE_PGRS26 and PE_PGRS43) with a possible role in the pathogenesis of bone TB. Next, an osteoblast cell line model for bone TB was developed allowing for significant intracellular multiplication of M.tb. Interestingly, three virulence genes (Rv1046c, DppD and PE_PGRS26) identified from human bone TB microarray data were also found to be overexpressed by intracellular M. tuberculosis in osteoblast cell lines. Overall, these data demonstrate that M. tuberculosis alters its transcriptome as an adaptive strategy to survive in the host and establish infection in bone. Additionally, the in vitro osteoblast model we describe may facilitate our understanding of the pathogenesis of bone TB.

Bone disease as the first manifestation of systemic AL-amyloidosis

2020 ◽  
Vol 92 (7) ◽  
pp. 85-89
Author(s):  
L. P. Mendeleeva ◽  
I. G. Rekhtina ◽  
A. M. Kovrigina ◽  
I. E. Kostina ◽  
V. A. Khyshova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Disease ◽  
Plasma Cells ◽  
Interventricular Septum ◽  
Bone Destruction ◽  
Amyloid Deposition ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
Linear Type

Our case demonstrates severe bone disease in primary AL-amyloidosis without concomitant multiple myeloma. A 30-year-old man had spontaneous vertebral fracture Th8. A computed tomography scan suggested multiple foci of lesions in all the bones. In bone marrow and resected rib werent detected any tumor cells. After 15 years from the beginning of the disease, nephrotic syndrome developed. Based on the kidney biopsy, AL-amyloidosis was confirmed. Amyloid was also detected in the bowel and bone marrow. On the indirect signs (thickening of the interventricular septum 16 mm and increased NT-proBNP 2200 pg/ml), a cardial involvement was confirmed. In the bone marrow (from three sites) was found 2.85% clonal plasma cells with immunophenotype СD138+, СD38dim, СD19-, СD117+, СD81-, СD27-, СD56-. FISH method revealed polysomy 5,9,15 in 3% of the nuclei. Serum free light chain Kappa 575 mg/l (/44.9) was detected. Multiple foci of destruction with increased metabolic activity (SUVmax 3.6) were visualized on PET-CT, and an surgical intervention biopsy was performed from two foci. The number of plasma cells from the destruction foci was 2.5%, and massive amyloid deposition was detected. On CT scan foci of lesions differed from bone lesions at multiple myeloma. Bone fragments of point and linear type (button sequestration) were visualized in most of the destruction foci. The content of the lesion was low density. There was no extraossal spread from large zones of destruction. There was also spontaneous scarring of the some lesions (without therapy). Thus, the diagnosis of multiple myeloma was excluded on the basis based on x-ray signs, of the duration of osteodestructive syndrome (15 years), the absence of plasma infiltration in the bone marrow, including from foci of bone destruction by open biopsy. This observation proves the possibility of damage to the skeleton due to amyloid deposition and justifies the need to include AL-amyloidosis in the spectrum of differential diagnosis of diseases that occur with osteodestructive syndrome.

HUBUNGAN DUKUNGAN KELUARGA DENGAN HARGA DIRI (SELF ESTEEM) PENDERITA TUBERKULOSIS PARU DI WILAYAH EKS KAWEDANAN INDRAMAYU

2017 ◽  
Vol 5 (1) ◽  
pp. 32-39
Author(s):  
Dedeh Husnaniyah
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Self Esteem ◽  
Cross Sectional Study ◽  
P Value ◽  
Sectional Study ◽  
Cross Sectional

Tuberkulosis Paru merupakan penyakit menular yang disebabkan oleh Mycobacterium tuberculosis. Dampak TB Paru adalah penurunan daya tahan tubuh, kelemahan fisik, merugikan secara ekonomis dan dapat mengakibatkan isolasi sosial. Keadaan tersebut dapat mempengaruhi harga diri penderita TB Paru. Perubahan harga diri pada penderita TB Paru dapat mempengaruhi keberhasilan pengobatan, sehingga dibutuhkan adanya dukungan keluarga. Tujuan Penelitian ini adalah untuk mengidentifikasi pengaruh dukungan keluarga terhadap harga diri penderita TB Paru di Wilayah Puskesmas Eks Kawedanan Indramayu tahun 2015. Jenis penelitian ini adalah deskriptif analitik dengan rancangan penelitian cross sectional study. Pengambilan sampel dilakukan dengan tekhnik total sampling sebayak 45 responden. Hasil penelitian menunjukkan bahwa penderita TB Paru yang memiliki harga diri tinggi sebanyak 23 responden (51,1%) dan yang memiliki harga diri rendah sebanyak 22 responden (48,9%), penderita TB Paru yang mendapatkan dukungan keluarga sebanyak 26 responden (57,8 %) dan yang tidak mendapatkandukungan keluarga sebanyak 19 (42,2 %). Responden yang mendapatkan dukungan keluarga lebih banyak yang memiliki harga diri tinggi dibandingkan dengan responden yang tidak mendapatkan dukungan keluarga yaitu 69,6% dengan nilai p value = 0,047 (< 0,05). Simpulan dari penelitian ini adalah terdapat hubungandukungan keluarga denganharga diri penderita TB Paru. Hasil penelitian ini diharapkan dapat menjadi masukan bagi pemegang program TB untuk memberikan konseling terkait pentingnya dukungan keluarga bagi penderita TB Paru.

scholarly journals Hypoxia-induced CREB cooperates MMSET to modify chromatin and promote DKK1 expression in multiple myeloma

Oncogene ◽  
2021 ◽  
Author(s):  
Yinyin Xu ◽  
Jing Guo ◽  
Jing Liu ◽  
Ying Xie ◽  
Xin Li ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Combined Treatment ◽  
Hypoxia Inducible Factor ◽  
Bone Destruction ◽  
Bone Lesions ◽  
Myeloma Cells ◽  
Downstream Target ◽  
Dkk1 Expression

AbstractMyeloma cells produce excessive levels of dickkopf-1 (DKK1), which mediates the inhibition of Wnt signaling in osteoblasts, leading to multiple myeloma (MM) bone disease. Nevertheless, the precise mechanisms underlying DKK1 overexpression in myeloma remain incompletely understood. Herein, we provide evidence that hypoxia promotes DKK1 expression in myeloma cells. Under hypoxic conditions, p38 kinase phosphorylated cAMP-responsive element-binding protein (CREB) and drove its nuclear import to activate DKK1 transcription. In addition, high levels of DKK1 were associated with the presence of focal bone lesions in patients with t(4;14) MM, overexpressing the histone methyltransferase MMSET, which was identified as a downstream target gene of hypoxia-inducible factor (HIF)-1α. Furthermore, we found that CREB could recruit MMSET, leading to the stabilization of HIF-1α protein and the increased dimethylation of histone H3 at lysine 36 on the DKK1 promoter. Knockdown of CREB in myeloma cells alleviated the suppression of osteoblastogenesis by myeloma-secreted DKK1 in vitro. Combined treatment with a CREB inhibitor and the hypoxia-activated prodrug TH-302 (evofosfamide) significantly reduced MM-induced bone destruction in vivo. Taken together, our findings reveal that hypoxia and a cytogenetic abnormality regulate DKK1 expression in myeloma cells, and provide an additional rationale for the development of therapeutic strategies that interrupt DKK1 to cure MM.

1,3-Diarylpyrazolyl-acylsulfonamides as Potent Anti-tuberculosis Agents Targeting Cell Wall Biosynthesis in Mycobacterium tuberculosis

2021 ◽  
Vol 64 (17) ◽  
pp. 12790-12807
Author(s):  
Lutete Peguy Khonde ◽  
Rudolf Müller ◽  
Grant A. Boyle ◽  
Virsinha Reddy ◽  
Aloysius T. Nchinda ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Cell Wall Biosynthesis

scholarly journals Drug Targeting Mycobacterium tuberculosis Cell Wall Synthesis: Development of a Microtiter Plate-Based Screen for UDP-Galactopyranose Mutase and Identification of an Inhibitor from a Uridine-Based Library

2003 ◽  
Vol 47 (1) ◽  
pp. 378-382 ◽  
Author(s):  
Michael S. Scherman ◽  
Katharine A. Winans ◽  
Richard J. Stern ◽  
Victoria Jones ◽  
Carolyn R. Bertozzi ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Drug Targeting ◽  
Enzyme Inhibitor ◽  
Microtiter Plate ◽  
Biosynthetic Enzyme ◽  
Cell Wall Synthesis ◽  
Chemical Library ◽  
Microtiter Plate Assay ◽  
Plate Assay

ABSTRACT A microtiter plate assay for UDP-galactopyranose mutase, an essential cell wall biosynthetic enzyme of Mycobacterium tuberculosis, was developed. The assay is based on the release of tritiated formaldehyde from UDP-galactofuranose but not UDP-galactopyranose by periodate and was used to identify a uridine-based enzyme inhibitor from a chemical library.

Activation of JNK and PAK2 is essential for citrinin-induced apoptosis in a human osteoblast cell line

2009 ◽  
Vol 24 (4) ◽  
pp. 343-356 ◽  
Author(s):  
Yu-Ting Huang ◽  
Ching-Yu Lai ◽  
Shyh-Liang Lou ◽  
Jui-Ming Yeh ◽  
Wen-Hsiung Chan
Keyword(s):  
Cell Line ◽  
Human Osteoblast ◽  
Osteoblast Cell ◽  
Human Osteoblast Cell ◽  
Osteoblast Cell Line ◽  
Induced Apoptosis

scholarly journals HUBUNGAN EFIKASI DIRI DENGAN KEPATUHAN MINUM OBAT PADA PASIEN TBC DI WILAYAH KERJA PUSKESMAS PARONGPONG KECAMATAN PARONGPONG KABUPATEN BANDUNG BARAT

2020 ◽  
Vol 5 (2) ◽  
pp. 186-193
Author(s):  
Mella Yusef Fintiya ◽  
Imanuel Sri Mei Wulandari
Keyword(s):  
Mycobacterium Tuberculosis ◽  
P Value ◽  
Cross Sectional ◽  
Purposive Sampling ◽  
Pearson's R ◽  
Pearson’S R

Tuberkulosis adalah penyakit infeksi paru yang disebabkan oleh Mycobacterium Tuberculosis. Di Indonesia kasus tuberkulosis setiap tahunnya semakin meningkat. Indonesia menepati urutan ke-6 penderita tuberkulosis tertinggi di dunia, sedangkan Jawa Barat menepati urutan pertama. Tujuan penelitian ini adalah untuk melihat adanya hubungan anatar efikasi diri dengan kepatuhan minum obat OAT. Metode penelitian menggunakan desain deskriptif korelasional dengan pendekatan cross sectional dengan melibatkan 23 responden yang sedang menjalani pengobatan di puskesmas parongpong, responden dipilih dengan menggunakan Purposive sampling. Variabel independen adalah efikasi diri, variabel dependent adalah kepatuhan minum obat. Instrumen dalam penelitian ini adalah kuesioner yang dianalisis menggunakan pearson’s r . Hasil dan analisis Efikasi Diri dengan Kepatuhan Minum obat mempunyai hubungan  dengan nilai  p-value 0,030 atau (p ≤ 0,05) dengan tingkat hubungan sedang (0,454). Efikasi merupakan salah satu faktor yang mempengaruhi kepatuhan minum obat pasien tuberkulosis di wilayah kerja Puskesmas Parongpong. Saran untuk penelitian selanjutnya perlu mengetahui peran kader kesehatan dalam kepatuhan minum obat.

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