Genetic information is not transmitted solely by DNA but by the epigenetics process. Epigenetics ... more Genetic information is not transmitted solely by DNA but by the epigenetics process. Epigenetics describes molecular missing link pathways that could bridge the gap between the genetic background and environmental risk factors that contribute to the pathogenesis of pulmonary fibrosis. Specific epigenetic patterns, especially DNA methylation, histone modifications, long non-coding, and microRNA (miRNAs), affect the endophenotypes underlying the development of idiopathic pulmonary fibrosis (IPF). Among all the epigenetic marks, DNA methylation modifications have been the most widely studied in IPF. This review summarizes the current knowledge concerning DNA methylation changes in pulmonary fibrosis and demonstrates a promising novel epigenetics-based precision medicine.
Purine nucleotides and nucleosides are involved in various human physiological and pathological m... more Purine nucleotides and nucleosides are involved in various human physiological and pathological mechanisms. The pathological deregulation of purinergic signaling contributes to various chronic respiratory diseases. Among the adenosine receptors, A2B has the lowest affinity such that it was long considered to have little pathophysiological significance. Many studies suggest that A2BAR plays protective roles during the early stage of acute inflammation. However, increased adenosine levels during chronic epithelial injury and inflammation might activate A2BAR, resulting in cellular effects relevant to the progression of pulmonary fibrosis.
ABSTRAK Merokok dapat menaikkan risiko penyakit paru-paru kronis, salah satunya TB Paru. Jumlah r... more ABSTRAK Merokok dapat menaikkan risiko penyakit paru-paru kronis, salah satunya TB Paru. Jumlah rokok per hari dapat memperburuk infeksi TB paru dan menyebabkan kegagalan konversi pada fase intensifikasi. Tujuan penelitian ini adalah untuk mengetahui profil perilaku merokok terhadap kejadian TB paru MDR di RSUD Dr. Soetomo Surabaya. Jenis penelitian ini adalah deskriptif observasional dengan metode retrospektif dan menggunakan data sekunder dari rekam medik pasien RSUD Dr. Soetomo Surabaya. Pengambilan sampel menggunakan total sampling. Hasil penelitian menunjukkan bahwa sebagian besar pasien TB paru MDR tidak merokok sebanyak 66 (56,4%) pasien, sebagian besar pasien TB paru MDR berumur 25- 45 tahun sebanyak 40 (34,2%) pasien dengan rata-rata umur 43,8 tahun, sebagian besar pasien TB paru MDR tidak memiliki penyakit komorbid sebanyak 68 (58,1%) pasien, sebagian besar pasien TB paru MDR berjenis kelamin laki-laki sebanyak 70 (59,8%) pasien, Rata-rata berat badan pasien TB paru MDR ad...
Background Chronic obstructive pulmonary disease (COPD) is a health problem that results in death... more Background Chronic obstructive pulmonary disease (COPD) is a health problem that results in death, commonly due to the development of pulmonary hypertension (PH). Here, by utilizing a mouse model of intratracheal elastase-induced emphysema that presents three different phases of COPD, we sought to observe whether budesonide/glycopyrronium/formoterol fumarate (BGF) triple therapy could prevent COPD-PH in addition to ameliorating COPD progression. Methods We utilized intratracheal elastase-induced emphysema mouse model and performed experiments in three phases illustrating COPD progression: inflammatory (1 day post-elastase), emphysema (3 weeks post-elastase) and PH (4 weeks post-elastase), while treatments of BGF and controls (vehicle, one-drug, and two-drug combinations) were started in prior to elastase instillation (inflammatory phase), at day 7 (emphysema), or at day 14 (PH phase). Phenotype analyses were performed in each phase. In vitro, A549 cells or isolated mouse lung endoth...
Background: Empirical antibiotics among outpatients with Lower Respiratory Tract Infections (LRTI... more Background: Empirical antibiotics among outpatients with Lower Respiratory Tract Infections (LRTIs) are scarcely allocated in Indonesia. The study aims to evaluate the pathogens causing LRTIs, drug sensitivity test and the minimum inhibitory concentrations of 90% (MIC90) of Cefditoren, Azithromycin, Amoxicillin-Clavulanic Acid, and Cefixime. Methods: The study was performed in adult outpatients with LRTI that can be expectorated. Patients with diabetes mellitus, HIV, lung tuberculosis, renal or hepatic failure, and hemoptysis were excluded. We performed bacterial culture, antibiotic sensitivity, and MIC measurement of four antibiotics. Results: There were 126 patients with LRTIs, and 61 patients were eligible for the study. We identified 69 bacteria. We found Klebsiella pneumonia (n=16; 26.23%), Staphylococcus aureus (n=11; 18%), Pseudomonas aeruginosa (n=8; 13.11%), Acinetobacter baumanii complex (n= 4; 6.55%), Streptococcus pneumonia (n=3; 4.9%) and others bacteria as causes of LR...
CTGF is upregulated in patients with idiopathic pulmonary fibrosis (IPF), characterized by the de... more CTGF is upregulated in patients with idiopathic pulmonary fibrosis (IPF), characterized by the deposition of a pathological extracellular matrix (ECM). Additionally, many omics studies confirmed that aberrant cellular senescence-associated mitochondria dysfunction and metabolic reprogramming had been identified in different IPF lung cells (alveolar epithelial cells, alveolar endothelial cells, fibroblasts, and macrophages). Here, we reviewed the role of the CTGF in IPF lung cells to mediate anomalous senescence-related metabolic mechanisms that support the fibrotic environment in IPF.
Adenosine is involved in a range of physiological and pathological effects through membrane-bound... more Adenosine is involved in a range of physiological and pathological effects through membrane-bound receptors linked to G proteins. There are four subtypes of adenosine receptors, described as A1AR, A2AAR, A2BAR, and A3AR, which are the center of cAMP signal pathway-based drug development. Several types of agonists, partial agonists or antagonists, and allosteric substances have been synthesized from these receptors as new therapeutic drug candidates. Research efforts surrounding A1AR and A2AAR are perhaps the most enticing because of their concentration and affinity; however, as a consequence of distressing conditions, both A2BAR and A3AR levels might accumulate. This review focuses on the biological features of each adenosine receptor as the basis of ligand production and describes clinical studies of adenosine receptor-associated pharmaceuticals in human diseases.
The hedgehog (Hh) pathway is a sophisticated conserved cell signaling pathway that plays an essen... more The hedgehog (Hh) pathway is a sophisticated conserved cell signaling pathway that plays an essential role in controlling cell specification and proliferation, survival factors, and tissue patterning formation during embryonic development. Hh signal activity does not entirely disappear after development and may be reactivated in adulthood within tissue-injury-associated diseases, including idiopathic pulmonary fibrosis (IPF). The dysregulation of Hh-associated activating transcription factors, genomic abnormalities, and microenvironments is a co-factor that induces the initiation and progression of IPF.
Introduction: Gastrointestinal tuberculosis (GI TB) is quite rare with 3% incidence of all extrap... more Introduction: Gastrointestinal tuberculosis (GI TB) is quite rare with 3% incidence of all extrapulmonary involvement. Appendicular TB may occur in 0.1 - 3% of cases. Diagnosis is often difficult because the patient usually complains about chronic abdominal pain and fever. A definite diagnosis is based on histopathological examination of resected specimens from the appendectomy procedure.Case: We present a 37-year-old male patient admitted to the hospital with chronic abdominal pain, fever, nausea, and loss of body weight. The patient never had a persistent cough, hemoptysis, or night sweating. Physical examination showed pain and muscular rigidity in the right iliac area during palpation with Blumberg's sign and Rovsing's sign positive. Abdomen ultrasound imaging showed an appendicular abscess. The patient underwent appendectomy afterwards with histopathology result showing TB. The patient was treated with first category anti-tuberculosis drugs (ATD).Discussion: Diagnosis o...
Idiopathic pulmonary fibrosis (IPF), one of the most common fibrosing interstitial lung diseases ... more Idiopathic pulmonary fibrosis (IPF), one of the most common fibrosing interstitial lung diseases (ILD), is a chronic-age-related respiratory disease that rises from repeated micro-injury of the alveolar epithelium. Environmental influences, intrinsic factors, genetic and epigenetic risk factors that lead to chronic inflammation might be implicated in the development of IPF. The exact triggers that initiate the fibrotic response in IPF remain enigmatic, but there is now increasing evidence supporting the role of chronic exposure of viral infection. During viral infection, activation of the NLRP3 inflammasome by integrating multiple cellular and molecular signaling implicates robust inflammation, fibroblast proliferation, activation of myofibroblast, matrix deposition, and aberrant epithelial-mesenchymal function. Overall, the crosstalk of the NLRP3 inflammasome and viruses can activate immune responses and inflammasome-associated molecules in the development, progression, and exacerb...
The innate immune system identifies exogenous threats or endogenous stress through germline-encod... more The innate immune system identifies exogenous threats or endogenous stress through germline-encoded receptors called pattern recognition receptors (PRRs) that initiate consecutive downstream signaling pathways to control immune responses. However, the contribution of the immune system and inflammation to fibrosing interstitial lung diseases (ILD) remains poorly understood. Immunoreceptor tyrosine-based motif-bearing C-type lectin-like receptors (CTLRs) may interact with various immune cells during tissue injury and wound repair processes. Dectin-1 is a CTLR with dominant mechanisms manifested through its intracellular signaling cascades, which regulate fibrosis-promoting properties through gene transcription and cytokine activation. Additionally, immune impairment in ILD facilitates microbiome colonization; hence, Dectin-1 is the master protector in host pulmonary defense against fungal invasion. Recent progress in determining the signaling pathways that control the balance of fibro...
Genetic information is not transmitted solely by DNA but by the epigenetics process. Epigenetics ... more Genetic information is not transmitted solely by DNA but by the epigenetics process. Epigenetics describes molecular missing link pathways that could bridge the gap between the genetic background and environmental risk factors that contribute to the pathogenesis of pulmonary fibrosis. Specific epigenetic patterns, especially DNA methylation, histone modifications, long non-coding, and microRNA (miRNAs), affect the endophenotypes underlying the development of idiopathic pulmonary fibrosis (IPF). Among all the epigenetic marks, DNA methylation modifications have been the most widely studied in IPF. This review summarizes the current knowledge concerning DNA methylation changes in pulmonary fibrosis and demonstrates a promising novel epigenetics-based precision medicine.
Purine nucleotides and nucleosides are involved in various human physiological and pathological m... more Purine nucleotides and nucleosides are involved in various human physiological and pathological mechanisms. The pathological deregulation of purinergic signaling contributes to various chronic respiratory diseases. Among the adenosine receptors, A2B has the lowest affinity such that it was long considered to have little pathophysiological significance. Many studies suggest that A2BAR plays protective roles during the early stage of acute inflammation. However, increased adenosine levels during chronic epithelial injury and inflammation might activate A2BAR, resulting in cellular effects relevant to the progression of pulmonary fibrosis.
ABSTRAK Merokok dapat menaikkan risiko penyakit paru-paru kronis, salah satunya TB Paru. Jumlah r... more ABSTRAK Merokok dapat menaikkan risiko penyakit paru-paru kronis, salah satunya TB Paru. Jumlah rokok per hari dapat memperburuk infeksi TB paru dan menyebabkan kegagalan konversi pada fase intensifikasi. Tujuan penelitian ini adalah untuk mengetahui profil perilaku merokok terhadap kejadian TB paru MDR di RSUD Dr. Soetomo Surabaya. Jenis penelitian ini adalah deskriptif observasional dengan metode retrospektif dan menggunakan data sekunder dari rekam medik pasien RSUD Dr. Soetomo Surabaya. Pengambilan sampel menggunakan total sampling. Hasil penelitian menunjukkan bahwa sebagian besar pasien TB paru MDR tidak merokok sebanyak 66 (56,4%) pasien, sebagian besar pasien TB paru MDR berumur 25- 45 tahun sebanyak 40 (34,2%) pasien dengan rata-rata umur 43,8 tahun, sebagian besar pasien TB paru MDR tidak memiliki penyakit komorbid sebanyak 68 (58,1%) pasien, sebagian besar pasien TB paru MDR berjenis kelamin laki-laki sebanyak 70 (59,8%) pasien, Rata-rata berat badan pasien TB paru MDR ad...
Background Chronic obstructive pulmonary disease (COPD) is a health problem that results in death... more Background Chronic obstructive pulmonary disease (COPD) is a health problem that results in death, commonly due to the development of pulmonary hypertension (PH). Here, by utilizing a mouse model of intratracheal elastase-induced emphysema that presents three different phases of COPD, we sought to observe whether budesonide/glycopyrronium/formoterol fumarate (BGF) triple therapy could prevent COPD-PH in addition to ameliorating COPD progression. Methods We utilized intratracheal elastase-induced emphysema mouse model and performed experiments in three phases illustrating COPD progression: inflammatory (1 day post-elastase), emphysema (3 weeks post-elastase) and PH (4 weeks post-elastase), while treatments of BGF and controls (vehicle, one-drug, and two-drug combinations) were started in prior to elastase instillation (inflammatory phase), at day 7 (emphysema), or at day 14 (PH phase). Phenotype analyses were performed in each phase. In vitro, A549 cells or isolated mouse lung endoth...
Background: Empirical antibiotics among outpatients with Lower Respiratory Tract Infections (LRTI... more Background: Empirical antibiotics among outpatients with Lower Respiratory Tract Infections (LRTIs) are scarcely allocated in Indonesia. The study aims to evaluate the pathogens causing LRTIs, drug sensitivity test and the minimum inhibitory concentrations of 90% (MIC90) of Cefditoren, Azithromycin, Amoxicillin-Clavulanic Acid, and Cefixime. Methods: The study was performed in adult outpatients with LRTI that can be expectorated. Patients with diabetes mellitus, HIV, lung tuberculosis, renal or hepatic failure, and hemoptysis were excluded. We performed bacterial culture, antibiotic sensitivity, and MIC measurement of four antibiotics. Results: There were 126 patients with LRTIs, and 61 patients were eligible for the study. We identified 69 bacteria. We found Klebsiella pneumonia (n=16; 26.23%), Staphylococcus aureus (n=11; 18%), Pseudomonas aeruginosa (n=8; 13.11%), Acinetobacter baumanii complex (n= 4; 6.55%), Streptococcus pneumonia (n=3; 4.9%) and others bacteria as causes of LR...
CTGF is upregulated in patients with idiopathic pulmonary fibrosis (IPF), characterized by the de... more CTGF is upregulated in patients with idiopathic pulmonary fibrosis (IPF), characterized by the deposition of a pathological extracellular matrix (ECM). Additionally, many omics studies confirmed that aberrant cellular senescence-associated mitochondria dysfunction and metabolic reprogramming had been identified in different IPF lung cells (alveolar epithelial cells, alveolar endothelial cells, fibroblasts, and macrophages). Here, we reviewed the role of the CTGF in IPF lung cells to mediate anomalous senescence-related metabolic mechanisms that support the fibrotic environment in IPF.
Adenosine is involved in a range of physiological and pathological effects through membrane-bound... more Adenosine is involved in a range of physiological and pathological effects through membrane-bound receptors linked to G proteins. There are four subtypes of adenosine receptors, described as A1AR, A2AAR, A2BAR, and A3AR, which are the center of cAMP signal pathway-based drug development. Several types of agonists, partial agonists or antagonists, and allosteric substances have been synthesized from these receptors as new therapeutic drug candidates. Research efforts surrounding A1AR and A2AAR are perhaps the most enticing because of their concentration and affinity; however, as a consequence of distressing conditions, both A2BAR and A3AR levels might accumulate. This review focuses on the biological features of each adenosine receptor as the basis of ligand production and describes clinical studies of adenosine receptor-associated pharmaceuticals in human diseases.
The hedgehog (Hh) pathway is a sophisticated conserved cell signaling pathway that plays an essen... more The hedgehog (Hh) pathway is a sophisticated conserved cell signaling pathway that plays an essential role in controlling cell specification and proliferation, survival factors, and tissue patterning formation during embryonic development. Hh signal activity does not entirely disappear after development and may be reactivated in adulthood within tissue-injury-associated diseases, including idiopathic pulmonary fibrosis (IPF). The dysregulation of Hh-associated activating transcription factors, genomic abnormalities, and microenvironments is a co-factor that induces the initiation and progression of IPF.
Introduction: Gastrointestinal tuberculosis (GI TB) is quite rare with 3% incidence of all extrap... more Introduction: Gastrointestinal tuberculosis (GI TB) is quite rare with 3% incidence of all extrapulmonary involvement. Appendicular TB may occur in 0.1 - 3% of cases. Diagnosis is often difficult because the patient usually complains about chronic abdominal pain and fever. A definite diagnosis is based on histopathological examination of resected specimens from the appendectomy procedure.Case: We present a 37-year-old male patient admitted to the hospital with chronic abdominal pain, fever, nausea, and loss of body weight. The patient never had a persistent cough, hemoptysis, or night sweating. Physical examination showed pain and muscular rigidity in the right iliac area during palpation with Blumberg's sign and Rovsing's sign positive. Abdomen ultrasound imaging showed an appendicular abscess. The patient underwent appendectomy afterwards with histopathology result showing TB. The patient was treated with first category anti-tuberculosis drugs (ATD).Discussion: Diagnosis o...
Idiopathic pulmonary fibrosis (IPF), one of the most common fibrosing interstitial lung diseases ... more Idiopathic pulmonary fibrosis (IPF), one of the most common fibrosing interstitial lung diseases (ILD), is a chronic-age-related respiratory disease that rises from repeated micro-injury of the alveolar epithelium. Environmental influences, intrinsic factors, genetic and epigenetic risk factors that lead to chronic inflammation might be implicated in the development of IPF. The exact triggers that initiate the fibrotic response in IPF remain enigmatic, but there is now increasing evidence supporting the role of chronic exposure of viral infection. During viral infection, activation of the NLRP3 inflammasome by integrating multiple cellular and molecular signaling implicates robust inflammation, fibroblast proliferation, activation of myofibroblast, matrix deposition, and aberrant epithelial-mesenchymal function. Overall, the crosstalk of the NLRP3 inflammasome and viruses can activate immune responses and inflammasome-associated molecules in the development, progression, and exacerb...
The innate immune system identifies exogenous threats or endogenous stress through germline-encod... more The innate immune system identifies exogenous threats or endogenous stress through germline-encoded receptors called pattern recognition receptors (PRRs) that initiate consecutive downstream signaling pathways to control immune responses. However, the contribution of the immune system and inflammation to fibrosing interstitial lung diseases (ILD) remains poorly understood. Immunoreceptor tyrosine-based motif-bearing C-type lectin-like receptors (CTLRs) may interact with various immune cells during tissue injury and wound repair processes. Dectin-1 is a CTLR with dominant mechanisms manifested through its intracellular signaling cascades, which regulate fibrosis-promoting properties through gene transcription and cytokine activation. Additionally, immune impairment in ILD facilitates microbiome colonization; hence, Dectin-1 is the master protector in host pulmonary defense against fungal invasion. Recent progress in determining the signaling pathways that control the balance of fibro...
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