BioMedicine-Taiwan最新文献

The intricately orchestrated progression of mammary tissue development involves the precise coordination of gland differentiation and cellular proliferation. Nevertheless, the understanding of the role and regulatory mechanisms governing the DNA replication machinery in mammary gland development remains limited. Given the essential role of DNA replication in the viability of living cells, any genetic disturbance to its replicative function, in any form, will impede organ development. This circumstance poses a technical challenge in elucidating the potential function of cell proliferation in mammary morphogenesis. PCNA is crucial in DNA replication, playing a pivotal role in the development of complete eukaryotic organisms. The phosphorylation of PCNA at tyrosine 211 (Y211) has been demonstrated to play a significant role in supporting replication forks and, consequently, cell proliferation. Therefore, the utilization of a knock-in mouse model, wherein the Y211 residue of PCNA is replaced with phenylalanine (211F), presents an opportunity to evaluate the impact of reduced cell proliferation potential on mammary gland development. Interestingly, the lack of Y211 phosphorylation did not significantly impact the rates of proliferation or cell death in the mammary gland. In contrast, the absence of Y211PCNA led to an increased, rather than reduced, growth of the mammary gland. This was evident in assessments of gland length and the number of terminal end buds (TEBs) in both postnatal and virgin mammary glands. Notably, this observation correlated with an elevation in tissue stemness within the 211F glands compared to the WT glands. Additionally, it was consistent with the greater body weight gains observed in 211F pups compared to WT pups during the weaning period. Our findings unveil an unexpected aspect that may carry significance for mammary development. This newfound is associated with the regulation of a central component within the DNA replication machinery, providing insights into the intricate interplay governing mammary tissue expansion.

Background: Traumatic brain injury (TBI) is a severe health problem for which there is no specific treatment, leading to neurological or neuropsychological consequences. One of the most described disorders, even after mild TBI (mTBI), is depression, related to mechanisms involving reactive oxygen species (ROS). The Mucuna pruriens (M. pruriens) plant has various antioxidant, neuroprotective, and anti-inflammatory properties.

Purpose: There is insufficient evidence of M. pruriens use for the treatment of neurobehavioral and depressive impairments induced by TBI and of the mechanisms underlying this effect, so we aimed to evaluate the ability of shortterm administration of M. pruriens extract to prevent neurobehavioral impairment and depression-like behaviors in a murine model of mTBI as well as evaluate the role of oxidative stress.

Methods: Male Wistar rats underwent mTBI or sham surgery. Immediately after, they were treated with vehicle or M. pruriens extract (50 mg/kg ip/day for five days). We evaluated neurobehavioral recovery using the Neurobehavioral Severity Scale-Revised (NSS-R) and the immobility time in the forced swimming test 3, 7, 15, 30, and 60 days after mTBI. In addition, lipid peroxidation (LP) and GSH concentrations were determined in some brain areas (motor cortex, striatum, midbrain, and nucleus accumbens).

Results: M. pruriens extract did not decrease neurobehavioral impairment caused by mTBI. Nevertheless, it prevented depression-like behaviors starting three days after mTBI, reduced LP, and increased GSH in some brain areas. Conclusions: M. pruriens may prevent depression-like behaviors and reduce oxidative stress by decreasing LP and increasing concentrations of antioxidant compounds.

Purpose: Phytochemicals have been found effective in reducing the oxidative stress and damage to cardiovascular and other tissues. In this study, the effects of alantolactone (AL) on cardiac parameters in rabbits exposed to artificially-induced oxidative stress were investigated.

Method: The oxidative stress was induced in a group of White New Zealand rabbits by injecting 40% hydrogen peroxide solution (1 ml/kg body weight) thrice with an interval of 72 h. The hydrogen peroxide-treated animals were orally treated with AL extracted from the roots of Inula helenium (1 ml/kg repeated thrice after 72 h). Blood samples were taken before and after the hydrogen peroxide and AL treatments, and the sera were subjected to analysis of oxidative damage in terms of malondialdehyde content (MDA), total antioxidant activity (TAOA), linoleic acid reduction capacity (LARC), hydroxyl radical scavenging capacity (HRSC), 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity (DPPH RSC), superoxide dismutase activity (SOD) and catalase activity, and cardiac parameters including troponin-I content (Trop-I), creatine kinase-MB (CKMB), aspartate transaminase (AST).

Results: The hydrogen peroxide treatment substantially enhanced MDA content and SOD activity and decreased LARC, HRSC, DPPH, and catalase activity. The AL treatment significantly decreased MDA content, TAOA, Trop-I, CK-MB, and AST levels and increased LARC, DPPH RSC, HRSC, and catalase activity.

Conclusion: The observed effect of AL treatment on the animals' oxidative stress, antioxidant status, and cardiac biomarkers emphasizes that AL may effectively manage oxidative stress and cardiac damage.

Background: Stroke is the leading cause of mortality and morbidity worldwide, and an effective therapeutic strategy for the prevention of patients with cerebral ischemia induced brain injury is lacking. Traditional Chinese medicine with neuroprotective activities might be beneficial and provide alternative therapeutic opportunities for cerebral ischemia.

Purposes: This study aimed to evaluate the neuroprotection and possible mechanisms of Gueichih-Fuling-Wan (GFW), its' constitutive herbs, and their active compounds on cerebral ischemia/reperfusion (I/R)-induced brain injury in rodents.

Methods: Various doses of extracts (0.25, 0.5, and 1.0 g/kg) of GFW and five constituent herbs (Cinnamomi Cortex, CC; Poria cocos, PC; Paeonia lactifloa, PL; Paeonia suffruticosa, PS and Prunus perisica, PP) were orally administered. Different doses of active compounds (0.5, 1.0, and 2.0 mg/kg) of GFW such as cinnamaldehyde, cinnamic acid (from CC), paeoniflorin (from PL), and paeonol (from PS) were intraperitoneally administered. Their effects on cerebral ischemia/ reperfusion (I/R)induced brain injury in rodents were evaluated.

Results: GFW, its' constituent herbs, and the active compounds reduced the infarct area dose-dependently (***P < 0.001). Cinnamaldehyde showed the most significant reduction (***P < 0.001). Therefore, trans-cinnamaldehyde (TCA) was further used to evaluate the neuroprotective mechanism of the I/R-induced brain injury. TCA (10, 20, 30 mg/ kg, p.o.) showed an inhibitory effect of I/R-induced brain damage in mice in a dose-dependent manner. Besides, GFW and TCA dose-dependently reduced the COX-2 protein expression level, and TCA reduced the TUNEL (+) apoptosis. TCA dose-dependently increased the pro-survival NR2A and Bcl-2 protein expression level and decreased the pro-apoptotic NR2B and cytochrome c, caspase 9, and caspase 3 expression (***P < 0.001).

Conclusion: The above data revealed that GFW, its' constituent herbs, and active compounds protected against I/R-induced brain injury in rodents. TCA from CC might participate in GFW protecting against cerebral ischemia-induced brain injury by inhibiting neuroinflammation and apoptosis.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and synovial joint destruction.

Aims: The current study investigated the possible beneficial effect of zinc oxide nanoparticles doped curcumin (ZnONPs-DC) on the recovery of RA and antioxidant status of experimental rabbits.

Methods: RA was induced in experimental rabbits by injecting complete Freund's adjuvant and collagen type-II emulsion (100 μL/kg body weight) in the base of their tail. Arthritic rabbits were orally treated with ZnONPs, curcumin, and ZnONPs-DC(250 μL/kg bodyweight). Serumsamples fromthe control and study groupswere collected before and afterRAinduction and after treatment. The sera were subjected to analysis of biological markers of RA and antioxidant status.

Results: The complete Freund's adjuvant and collagen type II treatment resulted in positive rheumatoid factor and C-reactive protein elevated oxidative stress and decreased antioxidant potential. Each treatment showed the absence of rheumatoid factor and C-reactive protein decreased oxidative stress and improved antioxidant potential compared to the control. However, ZnONPs-DC treatment showed a comparatively higher decline in serum malondialdehyde MDA content and an elevation in the antioxidant activity of RA animals.

Conclusions: In conclusion, using zinc oxide nanoparticles-doped curcumin may be an effective anti-arthritic and anti-inflammatory drug in controlling RA.

Background: Metastasis of breast cancer cells to distant sites including lungs, liver, lymph node, brain and many more have substantially affected the overall survival outcome and distant metastasis free survival rate amongst the diseased individuals. Several pre-clinical and clinical studies were carried out to determine the potency of vigorous inhibitors but they extensively deteriorated the patient's quality of life. Hence, there exists an urgent need to explore potent natural remedy to fight against metastatic breast cancer.

Methods: Ayurvedic medicinal plants documented in literature for their ability to fight against breast cancer was screened and their respective active moieties were evaluated to exert inhibitory effect against MMP9. Drug like efficacy of phytochemicals were determined using Molecular docking, MD Simulation, ADMET and MM-PBSA and were further compared with synthetic analogs i.e. Doxycycline.

Results: Out of 1000 phytochemicals, 12 exerted highest binding affinity (BA) even more than -9.0 kcal/mol that was significantly higher in comparison to Doxycycline which exhibited BA of -7.3 kcal/mol. In comparison to 37 × 30 × 37 Å, 53 × 45 × 66 Å offered best binding site and the highest BA was exhibited by Viscosalactone at LYS104, ASP185, MET338, LEU39, ASN38. During MD Simulation, Viscosalactone-MMP9 complex remained stable for 20 ns and the kinetic, electrostatic and potential energies were observed to be better than Doxycycline. Furthermore, Viscosalactone obtained from Withania somnifera justified the Lipinski's Rule of 5.

Conclusion: Viscosalactone obtained from W. somnifera may act as promising drug candidate to fight against metastatic breast cancer.

Herpes simplex, varicella-zoster lesions, skin rashes, diabetes, snake bites and insect bites have all been treated by using Clinacanthus nutans (C. nutans). The pharmacological effects of C. nutans are influenced by the presence of terpenoids, flavonoids, alkaloids, phenolic acids, saponins, glycosides, steroids and tannins. This review focused on the phytochemical makeup, which varies geographically and is a subject of scarcely existing knowledge. C. nutans served as the primary search term, while the keywords "phytochemicals", "chemical component" and "phytochemistry" were used to search the literature in the Google Scholar, PubMed, Scopus and Web of Science databases. The articles pertinent to the subject were found and reviewed. The phytochemical composition of C. nutans varied depending on the region it was cultivated in, and was influenced by the environmental conditions, genetics, air temperature and postharvest practices.

Cancer stands as a significant contributor to global mortality rates, primarily driven by its progression and widespread dissemination. Despite notable strides in cancer therapy, the efficacy of current treatment strategies is compromised due to their inherent toxicity and the emergence of chemoresistance. Consequently, there is a critical need to evaluate alternative therapeutic approaches, with natural compounds emerging as promising candidates, showcasing demonstrated anticancer capabilities in various research models. This review manuscript presents a comprehensive examination of the regulatory mechanisms governing the expression of matrix metalloproteinases (MMPs) and delves into the potential therapeutic role of flavonoids as agents exhibiting specific anticancer activity against MMPs. The primary aim of this study is to elucidate the diverse functions associated with MMP production in cancer and to investigate the potential of flavonoids in modulating MMP expression to inhibit metastasis.

Background: Fatty acid synthase (FASN), a key rate-limiting enzyme in the fatty acid biosynthesis pathway has been identified to be overexpressed in breast cancer. This overexpression has been affiliated with poor prognosis and resistance to chemotherapeutics. Consequently, FASN has come into focus as an appealing potential target for breast cancer treatment. Available FASN inhibitors, however, are unstable and have been correlated with adverse side effects.

Objective: This present study aims to investigate the potential of Andrographis paniculata ethanolic crude extract (AP) as a potent FASN inhibitor in breast cancer cells.

Materials & methods: This study used MTT assay and flow cytometry analysis to measure cell viability and apoptosis following AP treatment (0-500 μg/mL). Furthermore, FASN protein expression was evaluated using immunocytochemistry whereas lipid droplet formation was quantified using Oil Red O staining. Literature-based identified AP phytochemicals were subjected to the prediction of molecular docking and ADMET properties.

Results: This study demonstrated that AP significantly reduced cell viability while inducing apoptosis in breast cancer cells. In addition, for the first time, exposure to AP was demonstrated to drastically reduce intracellular FASN protein expression and lipid droplet accumulation in EMT6 and MCF-7 breast cancer cells. Docking simulation analysis demonstrated AP phytochemicals may have exerted an inhibitory effect by targeting the FASN Thioesterase (TE) domain similarly to the known FASN inhibitor, Orlistat. Moreover, all AP phytochemicals also possessed drug-likeness properties which are in accordance with Lipinski's rule of five.

Conclusions: These results highlight the potential of A. paniculata ethanolic crude extract as a FASN inhibitor and hence might have the potential to be further developed as a potent chemotherapeutic drug for breast cancer treatment.

The overexpression of glutaminase is reported to influence cancer growth and metastasis through glutaminolysis. Upregulation of glutamine catabolism is recently recognized as a critical feature of cancer, and cancer cells are observed to reprogram glutamine metabolism to maintain its survival and proliferation. Special focus is given on the glutaminase isoform, GLS1 (kidney type glutaminase), as the other isoform GLS2 (Liver type glutaminase) acts as a tumour suppressor in some conditions. Glutaminolysis linked with autophagy, which is mediated via mTORC1, also serves as a promising target for cancer therapy. Glutamine also plays a vital role in maintaining redox homeostasis. Inhibition of glutaminase aggravates oxidative stress by reducing glutathione level, thus leading to apoptotic-mediated cell death in cancer cells Therefore, inhibiting the glutaminase activity using glutaminase inhibitors such as BPTES, DON, JHU-083, CB-839, compound 968, etc. may answer many intriguing questions behind the uncontrolled proliferation of cancer cells and serve as a prophylactic treatment for cancer. Earlier reports neither discuss nor provide perspectives on exact signaling gene or pathway. Hence, the present review highlights the plausible role of glutaminase in cancer and the current therapeutic approaches and clinical trials to target and inhibit glutaminase enzymes for better cancer treatment.