BioMedicine-Taiwan最新文献

An inherent genetic enzyme disorder in humans, known as glucose-6-phosphate dehydrogenase (G6PD) deficiency, arises due to specific mutations. While the prevailing approach for investigating G6PD variants involves biochemical analysis, the intricate structural details remain limited, impeding a comprehensive understanding of how different G6PD variants of varying classes impact their functionality. This study 22 examined the dynamic properties of G6PD wild types and six G6PD variants from 23 different classes using molecular dynamic simulation (MDS). The wild-type and variant 24 G6PD structures unveil high fluctuations within the amino acid range of 274-515, the structural NADP⁺ binding site, pivotal for enzyme dimerization. Specifically, two variants, G6PD_Zacatecas (R257L) and G6PD_Durham (K238R), demonstrate compromised structural stability at the dimer interface, attributable to the disruption of a salt bridge involving Glu 206 and Lys 407, along with the disturbance of hydrogen bonds formed by Asp 421 at the βN-βN sheets. Consequently, this impairment cascades to affect the binding affinity of crucial interactions, such as Lys 171-Glucose-6-Phosphate (G6P) and Lys 171-catalytic NADP⁺, leading to diminished enzyme activity. This study underscores the utility of computational in silico techniques in predicting the structural alterations and flexibility of G6PD variants. This insight holds promise for guiding future endeavors in drug development targeted at mitigating the impacts of G6PD deficiency.

Introduction: Diseases caused by bacteria can be managed with medicinal plants with rightful dosage that will not affect body physiology and organs.

Aim: This research aimed to evaluate the antioxidants and the effects of Anogeisus leiocarpus on liver function.

Materials and methods: Ethanol leaf extracts were processed for antioxidants and hepatotoxic effects using animal models. Group one (negative control) was given access to water and regular feed, group two (positive control) was dosed with 107 CFU/ml of Escherichia coli O157:H7, and groups 3-6 were dosed with 107 E. coli O157:H7 for 3 days and treated with extract concentrations of 12, 25, 50 and 100 mg/kg bw respectively for seven days.

Results: Higher ascorbic acid values in Ferric reducing antioxidant property (FRAP) and Hydroxyl radical scavenging (HRS) were recorded in the positive control (0.05 ± 0.01, 41 ± 0.05) than in the extract-treated (0.02 ± 0.14, 30 ± 0.02). Increase in DPPH (47 ± 0.1268 ± 0.05 %), Free radical scavenging property (FRAP) (0.03 ± 0.02-0.08 ± 0.14 %), and HRS (38 ± 0.14-68 ± 0.12 %) was observed in the extract. The lipid peroxidation (LPO) of the quote was 78.51 ± 2.16, GSH was 36.18 ± 3.18, and catalase was 78.42 ± 4.713. In the extract-treated, decreased values were recorded for LPO ((108.36 ± 1.12-70.19 ± 1.68 μM/g), while increased values were observed in Glutathione (GSH) (25.11 ± 2.64-33.62 ± 1.35 μM/g), and catalase (54.18 ± 2.14-60.25 ± 1.4 μM/g). The values of negative control for Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and Alkaline phosphate (ALP) were lesser than what was received in the extract treated.

Conclusion: The plant's traditional medicine usage is effective at low dosage and could be a suitable candidate for drug development which will not affect the body's physiology and organs. The subjecting of A. leiocarpus ethanol leaf extract to antioxidants assays and its effect on liver function have further proved its value in folklore medicine.

Aging is considered part of the natural process of life, however in recent years medical literature has started to show that specific facets of aging are beginning to be understood and those factors may even be considered preventable with various measures. Aging is also considered the number one cause of poor quality of life, disease, disability, and death, so the importance of understanding the aging process and how to control certain aspects of it cannot be underestimated when age related suffering is factored in. The causes of aging are now becoming well understood, and in recent years many therapies have already become available to the public to attenuate specific corridors of aging. The heterogeneity of the aging process and the biological drivers involved is examined here in parallel with various compounds and therapies to combat biological decline. The benefits for governments in keeping their populations healthy and vibrant are vast, and at the same time offer a great incentive to invest into newly emerging technologies that may prevent the onset of preventable disease. Whilst this paper only discusses nine pathways to the aging process, many more exist.

Mucus is a substance made by snails that serves a variety of purposes and is increasingly employed in the medical and cosmetic industries. It includes bioactive compounds with a range of biological characteristics that could be useful in the treatment of particular issues. This study assessed the wound-healing efficiency, antibacterial activity, chemical and mineral composition of Helix aspersa Müller slime. Inductively Coupled Argon Plasma Atomic Emission Spectrometry (ICP-OES) was used for mineral analysis, while Gas chromatography coupled to mass spectrometry (GC-MS) analysis was used for chemical characterization. The findings showed that the H. aspersa Müller slime had inhibitory activity on the test samples. Additionally, it revealed significant healing activity. These findings point to the chemical composition and various biological activities of the H. aspersa Müller slime, which may be related to the animal's particular functions and be useful for medical applications. Our findings suggest that the H. aspersa Müller slime has biological effects related to antimicrobial activities and wound healing, and they pave the way for a more thorough investigation of its potential therapeutic effects.

Gemcitabine is frequently utilized to treat pancreatic cancer. The purpose of our study was to create a gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cell line (MIA-GR100) and to evaluate the anti-pancreatic cancer efficacy of HMJ-38, a new quinazolinone analogue. Compared to their parental counterparts, MIA-PaCa-2, established MIA-GR100 cells were less sensitive to gemcitabine. MIA-GR100 cell viability was not affected by 10, 50 and 100 nM gemcitabine concentrations. HMJ-38 reduced MIA-GR100 cell growth and induced autophagy and apoptosis. When stained with monodansylcadaverine (MDC), acridine orange (AO), and terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), MIA-GR100 cells shrunk, punctured their membranes, and produced autophagy vacuoles and apoptotic bodies. Combining chloroquine (CQ) and 3-methyladenine (3-MA) with HMJ-38 dramatically reduced cell viability, indicating that autophagy function as a cytoprotective mechanism. MIA-GR100 cells treated with both z-VAD-FMK and HMJ-38 were much more viable than those treated with HMJ-38 alone. HMJ-38 promotes apoptosis in MIA-GR100 cells by activating caspases. Epidermal growth factor receptor (EGFR) is one of HMJ-38's principal targets, as determined via in silico target screening with network prediction. HMJ-38 also inhibited EGFR kinase activity and EGFR-associated signaling in MIA-GR100 cells. HMJ-38 may be an effective chemotherapeutic adjuvant for gemcitabine-resistant pancreatic cancer cells, in which it induces an antitumor response.

Introduction: Periodontitis is a common chronic inflammatory disease characterized by the destruction of the supporting structures of the teeth. The host defense mechanisms are responsible for inflamatuar and destructive reactions in periodontitis. Celastrol is one of the most promising components of the plant in Eastern and Southern China that has a long history of use in traditional medicine for the treatment of inflammatory conditions.

Aim: The aim of this animal study was to inspect the preventive or restrictive effects of celastrol on periodontitis-related inflammatory host response and alveolar bone loss.

Methods: 24 male Sprague Dawley rats were randomly assigned into 3 groups: control, experimental periodontitis (Ep), and experimental periodontitis-celastrol (Ep-Cel). Periodontitis was induced by placing ligatures sub-paramarginally around the mandibular first molars of the rats in the Ep and Ep-Cel groups and maintaining the ligatures for 15 days. For 14 days following the ligature placement, celastrol administration (1 mg/kg BW day) for the Ep-Cel group and vehicle injection for the control and Ep groups was carried out. At the end of the experiment, mandibula and gingiva samples were obtained after the euthanasia. Alveolar bone loss was measured on serial histological slices; Tumor Necrosis Factor-α and Interleukin-1β levels were measured on gingiva samples by ELISA.

Results: Systemic celastrol administration significantly restricted the alveolar bone loss that was higher in rats with periodontitis. (p < 0.05) Tumor Necrosis Factor-α and Interleukin-1β levels that were high in the gingiva of the rats with periodontitis were found significantly lower in rats administered celastrol. (p < 0.05).

Conclusion: Celastrol restricted periodontitis-related alveolar bone loss by suppressing the inflammatory response.

Spontaneous intracranial hypotension (SIH) is a poorly understood condition that presents with a wide variety of symptoms, ranging from mild headaches to coma. It is typically caused by continuous spontaneous leakage of spinal cerebrospinal fluid (CSF), resulting in orthostatic headaches. However, the appropriate management of refractory SIH remains unclear. A 50-year-old man presented with orthostatic headache followed by a rapid decline in mental status. The imaging findings were consistent with the diagnosis of SIH, with bilateral cerebral subdural hematomas and abnormal fluid collection in the posterior epidural space from the T2 to T12 levels. Computed tomography myelography of the whole spine revealed multiple high-flow CSF leakages at the T6 to T8 levels. Despite treatment with bilateral burr hole drainage for subdural hematomas and repeated lumbar epidural blood patch (EBP) three times, the patient's condition worsened and he developed stupor. A lumbar intrathecal saline bolus (90 ml) was administered to restore CSF depletion. The patient's verbal function improved immediately, and continuous intrathecal saline infusion was administered at a rate of 10 ml/h for two days. The patient's stupor gradually resolved, and after his symptoms improved, the EBP injection was repeated at the T8 level. The patient recovered completely, and during the six-year follow-up, there were no signs of recurrence. SIH may cause a refractory decline in mental status, and lumbar intrathecal saline infusion may help arrest or reverse an impending central (transtentorial) herniation. This case demonstrates an appropriate bolus and continuous infusion of normal saline, and documents the resolution of SIH. This maneuver may change the CSF flow pattern and aims to seal the CSF fistula. Further studies are needed to better understand the mechanism of intrathecal saline infusion and establish effective treatment strategies for refractory cases of SIH.

Although primary integrase strand transfer inhibitor resistance mutations are currently uncommon, the increasing use of integrase strand transfer inhibitor as a key component of the first, second and third-line antiretroviral regimens suggests that the prevalence of integrase drug resistance mutations will likely increase. The rise of several polymorphic mutations and natural polymorphisms also affects the level of susceptibility of human immunodeficiency virus (HIV) type-1 to integrase strand transfer inhibitor. The considerable variability among the various subtypes of human immunodeficiency virus type-1 may contribute to differences in integrase mutations associated with integrase strand transfer inhibitors. Notably, non-B subtypes of HIV type-1 (HIV-1) are the predominant cause of human immunodeficiency virus infection worldwide. The presence of diverse integrase drug resistance mutations can have significant implications on the administration of integrase strand transfer inhibitor-based antiretroviral therapy to patients with human immunodeficiency virus infection.

Background: Assessing high-risk mortality in acute coronary syndrome (ACS) patients, encompassing ST-Elevation Myocardial Infarction (STEMI), Non-ST-Elevation Myocardial Infarction (NSTEMI), and Unstable Angina Pectoris (UAP), is crucial. However, the prognostic significance of hematological parameters in predicting high-risk mortality in ACS patients remains uncertain despite advancements in ACS research.

Aim: The aim was to investigate prognostic significance of hematological parameters troponin, Creatine Kinase-MB (CKMB), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Monocyte-to-Lymphocyte Ratio (MLR), Basophil-to-Lymphocyte Ratio (BLR), and Eosinophil-to-Lymphocyte Ratio (ELR) levels in predicting high-risk mortality in ACS patients.

Methods: In this retrospective observational study, data from medical records of 115 patients with ACS, including 40 with STEMI, 38 with NSTEMI, and 37 with UAP, were analyzed. Patients were selected using stratified random sampling, whereby five patients were randomly chosen each month from January 2021 to December 2022 while maintaining a 1:1:1 ratio of selection.

Results: Troponin (r = 0.519) and NLR (r = 0.484) showed moderate positive correlations with high-risk STEMI mortality. Meanwhile, troponin (r = 0.387), NLR (r = 0.279), PLR (r = 0.276), MLR (r = 0.250), BLR (r = 0.237), and ELR (r = -0.344) were found to be significantly correlated with high-risk ACS mortality. Troponin, CKMB, NLR, and MLR were significant (AUC>0.7) for high-risk STEMI mortality, and Troponin, NLR, and MLR were significant for high-risk ACS mortality. The results of the multivariate regression analysis indicated that only Troponin (OR:2.049; 95%CI: 1.802-8.218; p = 0.014), NLR (OR:1.652; 95%CI: 1.306-7.753; p = 0.030), and MLR (OR:4.067; 95%CI: 1.182-13.987; p = 0.026) were capable of predicting high-risk ACS mortality. Sub-group analysis showed an increased risk of ACS mortality by GRACE score >140 in patients with elevated levels of Troponin (OR:2.787; 95%CI: 1.032-7.524; p < 0.05), NLR (OR:3.287; 95%CI: 1.340-8.059; p < 0.05), and MLR (OR:4.156; 95%CI: 1.634-10.569; p < 0.05) above the cut-off value.

Conclusion: Troponin, NLR, and MLR levels above the cutoff independently predict high-risk mortality in ACS.

Background: Embryo implantation is a complex biological process which requires synchronized dialogue between the receptive endometrium and the blastocyst. The endometrium, however, is only receptive to embryo implantation for a very short period. Recurrent implantation failure (RIF) is a major challenge in assisted reproductive techniques mainly due to impaired receptivity, but there is still a need for a reliable and valid clinical test to assess endometrial receptiveness, especially at embryo transfer time. The aim of this review is to investigate what is currently known about the contribution of endometrial fluid (EF) to endometrial receptivity by identifying its potential biomarkers.

Methods: This study involved an extensive search of the electronic databases PubMed and Cochrane, covering the period from 2011 to 2022. A combination of Medical Subject Headings with the terms 'endometrial fluid' and 'embryo implantation' was used.

Results: Several different proteins presented in the endometrial cavity fluid have been described but the most consistent as potential biomarkers were Proprotein Convertase 6 (PC6), Vascular Endothelial Growth Factor (VEGF), PIGF (Placental growth factor), β3 integrin, Colony Stimulating Factor-3 (CSF-3), Leukaemia inhibitory factor (LIF), glycodelin and extracellular vesicles (EVs).

Conclusions: Strong indicators support the use of uterine fluid collection as a non-invasive tool for receptivity assessment. Therefore, it could improve outcomes of assisted reproductive techniques.