Biomedical Research and Therapy

Results response of neoadjuvant chemotherapy for stage III breast carcinoma at Viet Nam National Cancer Hospital

Nguyen Truong Thien — 2024-11-30

Objective: To characterize the clinical and paraclinical features of stage III breast carcinoma (BC) and evaluate the response to neoadjuvant chemotherapy (NAC).

Methods: A cross-sectional study was conducted on 108 patients diagnosed with stage III breast cancer, who were treated with NAC, consisting of four cycles of Doxorubicin and Cyclophosphamide (4AC), followed by four cycles of Paclitaxel (4T).

Results: The average age of the patients was 45.16 ± 9.98 years (median age: 45 years), ranging from 29 to 66 years. According to the AJCC's 8^th edition (2017), the majority of patients were classified as stage IIIA (37.96%) and IIIB (38.89%), while 23.15% were in stage IIIC. Molecular subtypes included Luminal B in 60.66% of patients, HER2-positive in 42.59%, and triple-negative in 24.59%. The clinical response rate (based on RECIST 1.1 criteria) was 94.44% after four NAC cycles and improved to 97.22% after eight cycles. Histopathological assessment using the Chevallier classification showed a pathological complete response (pCR) rate of 29.63% and a near-complete response rate of 6.48%, with a residual disease (RD) rate of 63.89%.

Conclusion: The study revealed that stage III breast carcinoma predominantly affects women around the age of 45 (66.67% were under 50 years), with stage IIIB being the most common. Luminal B was the most prevalent molecular subtype, while HER2 positivity was high, accounting for 40.98%. The dose-dense NAC regimen (2-week cycles) of 4AC-4T demonstrated high efficacy, with over 97% of patients achieving a clinical response after eight cycles, based on RECIST 1.1 criteria. The pathological complete response (pCR) rate, according to the Chevallier classification, reached 29.63%, indicating significant tumor regression, while 70.37% exhibited residual disease, either invasive or in situ. These findings highlight the effectiveness of the dose-dense 4AC-4T NAC regimen in downstaging tumors and improving surgical outcomes in stage III breast cancer patients.

Platelet rich plasma driven changes in hepatic glycogen metabolism and hepato-histological assessment in diabetic mice

Amin Arif — 2024-11-30

Background: Platelet-rich plasma (PRP) emerges as a promising therapy, exhibiting noticeable anti-diabetic potential. Nevertheless, the precise underlying mechanism remains enigmatic. In the current investigation, we aimed to scrutinize the potential therapeutic ramifications of PRP in alloxan-induced diabetic mice, with a particular focus on its modulation of glycogen metabolism and glucose transport.

Methods: Forty mice were randomly divided into four groups: NC (Control), PC (PRP treatment), DC (Alloxan dose), and DT (Alloxan+PRP treatment). PRP was administered subcutaneously over four weeks, with a frequency of twice-weekly dosing, to diabetic mice.

Results: Our findings illustrate that PRP maintained glucose homeostasis through its modulatory influence on glycogen metabolism and glucose transporters (Glut2 and Glut4) on the hepatocyte membrane. PRP substantially reduced hepatic glycogen content significantly (P = 0.0148). Moreover, PRP treatment effectively preserved the structural integrity of hepatic lobules and maintained glycogen levels within the cells. There was a substantial increase in glycogen accumulation within the cytoplasm of liver cells in the diabetic group (DC). However, treatment with platelet-rich plasma (PRP) in the diabetes-treated (DT) group resulted in a marked improvement in glycogen accumulation within liver cells.

Conclusion: In aggregate, we concluded that PRP has the potential to ameliorate hyperglycemia in DM by orchestrating the interplay of glycogen metabolism and glucose transport within the liver, ultimately restoring glycogen deposition in hepatic tissues.

Association of P73, BMP15, and GDF9 gene polymorphisms with diminished ovarian reserve

Sina Ghasemifar — 2024-11-30

Introduction: Diminished ovarian reserve (DOR) is a condition in which the quantity or quality of oocytes results in impaired fertility. The prevalence of DOR in infertile women is estimated to be around 10%. Our aim was to investigate the polymorphisms rs3810682, rs10491279, and rs4648551 in association with the genes BMP15, GDF9, and p73 in patients with DOR and control samples.

Methods: Genomic DNA was isolated from 5 cc of peripheral blood from 300 participants (150 patients with DOR and 150 women without a history of DOR). After ARMS-PCR assay and sequencing of a series of samples to confirm results, data were analyzed using GraphPad Prism software.

Results: A significant difference was found between the frequencies of the different polymorphisms associated with the BMP15 gene (P value = 0.002). However, for the polymorphisms of the GDF9 and p73 genes, no significant difference was found between the frequencies of these polymorphisms in the control and patient groups.

Conclusion: Determining the frequency of gene variants in case and control groups helps in understanding the potential risk factors for the development of DOR. Understanding these factors is very important in different populations that naturally have different lifestyles, especially in a country like Iran, where a large number of pregnancies occur at older ages due to the use of contraceptives. Determining risk factors can help women decide when to become pregnant. Finally, further validation is needed to obtain more information on the use of the polymorphisms investigated in this study as an indicator of DOR in Iranian populations.

Platelet-rich plasma therapy for meibomian gland dysfunction and dry eye: A mini review

Sinh Truong Nguyen — 2024-11-30

A common eye condition known as dry eye syndrome is characterized by insufficient tear production or rapid tear evaporation, causing dryness, irritation, and pain. A common etiological cause for dry eye disease (DED) that affects both the composition and production of tears is meibomian gland dysfunction (MGD). Meibum, an oily substance produced by the meibomian glands, is essential for preventing tear evaporation. The temporary alleviation offered by standard dry eye therapies has prompted researchers to investigate new therapeutic modalities. Platelet-rich plasma (PRP) therapy has been identified as a viable approach for stimulating meibomian gland activity and improving tear production in dry eye patients. Highly concentrated platelets and growth factors found in PRP are essential for promoting tissue regeneration and accelerating the healing process. By the application or injection of PRP in the affected region, the growth factors could stimulate the production and release of meibum, thereby improving the functionality of the meibomian glands and reinstating the stability of the tear film. The objective of this review article is to conduct a comprehensive analysis of clinical evidence supporting the utilization of PRP therapy in managing MGD and dry eye syndrome. Several studies have demonstrated the efficacy of PRP therapy in enhancing meibomian gland function, mitigating ocular surface inflammation, and alleviating symptoms associated with dry eye. Based on the research outcomes, it has been determined that PRP therapy exhibits potential efficacy as a novel intervention for treating dry eye syndrome. This therapeutic approach demonstrates the ability to enhance the health of the ocular surface and target the fundamental etiological factors associated with this condition. Additional research and investigation are required to ascertain the optimal protocols and long-term efficacy of PRP therapy in treating dry eye and MGD. In conclusion, PRP therapy represents a promising and effective treatment option for patients suffering from dry eye syndrome and MGD, offering significant improvements in ocular surface health and patient quality of life.

miRNAs in Melanoma: Diagnostic, prognostic, and therapeutic strategies

Gulsah Evyapan — 2024-11-30

Melanoma is a highly aggressive and deadly form of skin cancer, with its incidence and mortality rates increasing significantly worldwide. Recent research suggests that miRNA-based therapies could help improve outcomes for melanoma patients by controlling gene expression at the posttranscriptional level, which affects how the tumor grows and spreads. This review aims to examine the role of microRNAs (miRNAs) in melanoma progression, highlighting their potential as therapeutic targets and exploring how they may be utilized in diagnostic and prognostic processes.

Primary evaluation the effects of Boesenbergia pandurata ethanol extract on etoposide-induced senescence in fibroblasts

Phuc Hong Vo — 2024-11-30

Introduction: Cellular senescence is an extensively researched issue aimed at influencing the aging process. A novel research direction involves studying the potential of plant extracts on this process. Boesenbergia pandurata (Roxb.) Schltr, also known as Boesenbergia rotunda (L.) Mansf, is a herb with significant potential for research into its effects on aging. Furthermore, it is crucial to study cellular senescence models to accurately assess the impact of various agents on the aging process.

Methods: In this study, the ethanol extract of Boesenbergia pandurata (Roxb.) Schltr was evaluated for its potential effects on certain characteristics of senescent fibroblasts derived from foreskin, which were induced by etoposide. The cells were treated with 20 μM etoposide for 48 hours to induce senescence.

Results: The study demonstrated that treating fibroblasts with 20 μM etoposide for 48 hours induces senescence characteristics. Additionally, administering the ethanol extract of Boesenbergia pandurata at a concentration of 15 μg/ml ameliorated several features of senescence in fibroblasts. The treatment resulted in a 27% reduction in cell size (p < 0.05), a 1.2-fold decrease in SA-β-Galactosidase enzyme activity (p < 0.0001), and reduced gene expression of p16, p21, and p53.

Conclusion: We established a senescent fibroblast model using 20 μM etoposide and demonstrated that the finger root extract at 15 μg/ml improved various senescence-related cellular characteristics, suggesting its potential as an anti-aging agent.

The relationship between MBL2 levels and NLRP3 in acute ischemic stroke: Insights from a proteomics study

Bin Zhu — 2024-11-30

Objective: Inflammation plays a pivotal role in the pathogenesis of stroke. However, the proteins that initiate inflammatory responses remain unclear. In this study, we utilize proteomics to identify the core protein in acute ischemic stroke (AIS) patients and verify the relationship of the protein with NOD-like receptor protein 3 (NLRP3).

Methods: Peripheral blood from AIS patients and patients without AIS was collected and analyzed using a quantitative proteomic method (label-free) to screen for differential proteins. Subsequently, the differential protein was validated by ELISA. Additionally, a middle cerebral artery occlusion (MCAO) model was utilized to explore the relationship between mannose-binding lectin 2 (MBL2) and NLRP3. Co-immunoprecipitation (Co-IP) and western blot were also used to validate the interaction between the proteins and NLRP3.

Results: A total of ten AIS patients and controls were enrolled in the proteomics study. Compared with the control group, a total of 49 proteins were identified as potential proteins. Among these proteins, MBL2 was notably increased in the AIS group and selected for further analysis. Subsequent ELISA analysis confirmed a significant elevation of MBL2 levels in stroke patients (P < 0.001). Further, in animal studies, Co-IP assays showed an interaction between MBL2 and NLRP3 proteins in cerebral tissue after ischemic infarction. Western blot results demonstrated that the expression levels of NLRP3 and MBL2 were significantly increased in MCAO rats.

Conclusions: Our results suggest that MBL2 may be one of the promoters of inflammation by interacting with NLRP3 in AIS patients.

Hemocyanin is a major allergen in local mud crab Scylla paramamosain in Viet Nam

Kieu-Minh Le — 2024-11-30

Introduction: Shellfish allergy is prevalent in coastal countries across Asia. Despite crab being a popular dish, there is limited knowledge about the features of crab allergy in Viet Nam. This study aims to identify the IgE-binding allergens in the local crab species, Scylla paramamosain (S. paramamosain).

Methods: The study involved 12 patients with crab allergy and 5 subjects with crab tolerance. Each participant underwent a skin prick test (SPT) with crab extracts and was measured for specific IgE levels to crab, as well as house dust mite species Dermatophagoides farinae (DF) and Dermatophagoides pteronyssinus (DP). An immunoblot was used to identify IgE-binding proteins in S. paramamosain, followed by identification using nanoscale liquid chromatography coupled with tandem mass spectrometry analysis.

Results: Patients with crab allergy exhibited higher total IgE levels (2432 ± 772.26 vs 886.15 ± 3056.74), 100% positive SPT to crab, and higher specific IgE levels to crab (3.40 ± 6.19 vs 0.48 ± 8.86) compared to subjects with crab tolerance. The level of specific IgE to crab showed significant correlation with SPT results to DP and DF (r = 0.52, P = 0.033; r = 0.82, P < 0.001, respectively). The frequencies of IgE-binding proteins in crab allergy patients were higher than in tolerant subjects. Several putative allergens were identified, including hemocyanin as a major allergen, with arginine kinase, sarcoplasmic-calcium binding protein, and triosephosphate isomerase as minor allergens.

Conclusion: This study is the first to demonstrate potential molecular allergens in local mud crabs among Vietnamese individuals sensitized to house dust mites. These findings require further clinical evaluation in future studies for their application.

A laboratory study on N-acetyl cysteine in SSP+ modulating oxidative stress and delaying the progression of storage lesion in platelets

Magdaline Christina Rajanand — 2024-11-30

Introduction: Oxidative stress (OS) contributes to platelet storage lesion (PSL) and can be attenuated by using antioxidant additives in the storage solution. N-acetyl cysteine (NAC), a thiolcontaining antioxidant, scavenges reactive oxygen species (ROS) directly, upregulates antioxidant defenses, and has anti-apoptotic properties. This study explores the effect of the antioxidant additive NAC on platelets during storage.

Methods: Platelets obtained from the blood of male Wistar rats (n = 5) were resuspended in SSP+ and divided into i) Controls, ii) 0.5-NAC, and iii) 1-NAC; stored at 22◦C for 11 days. The markers of platelet function (aggregation, ATP secretion, P-selectin), viability (caspase-3, MTT), OS (superoxides, nitrites), lipid peroxidation (thiobarbituric reactive substances), protein oxidation (protein sulfhydryls, advanced oxidation protein products), antioxidant defenses (superoxide dismutase, catalase, glutathione, total antioxidant capacity), and metabolism (pH, glucose, lactate dehydrogenase) were analyzed on storage days 1, 4, 7, and 11.

Results: 1- NAC augmented antioxidant defenses, improved viability, and decreased protein oxidation, lipid peroxidation, and platelet activation. Aggregation without collagen decreased in 0.5-NAC and 1- NAC compared to controls. Both 0.5-NAC and 1-NAC were effective in maintaining platelet functions during storage. However, 1-NAC protected platelets from oxidation, enhanced antioxidant defenses, and maintained viability until day 7 of storage. 1-NAC could effectively scavenge ROS and enhance GSH and antioxidant enzymes in comparison to 0.5-NAC.

Conclusion: N-acetyl cysteine at 1 mM concentration in SSP+ could maintain the efficacy of platelets as these cells could endure OS until day 7 of storage. This study emphasizes the potential of NAC as an effective component of platelet storage solutions to prolong the shelf-life of platelets.

The role of inflammation and oxidative stress markers in the occurrence and severity of coronary artery disease in young patients with ST-segment elevation myocardial infarction

Marwa A. Gaber — 2024-11-30

Background: Atherosclerosis is modulated by inflammation and oxidative stress, which play pivotal roles in the pathogenesis of coronary artery disease (CAD), especially in young patients without traditional risk factors for atherosclerosis. In this study, we aimed to study the role of some inflammatory and oxidative stress markers in triggering ST segment elevation myocardial infarction in Egyptian young patients and the potential correlation to the severity of coronary artery lesions in the Egyptian population.

Methods: This case-control study recruited 115 premature STEMI patients (aged <45 years) and 55 age-matched healthy controls. Serum CRP, TNF-a, IL-10, and oxidative stress biomarkers [reduced glutathione, total antioxidants, L-ascorbic acid, nitric oxide (NO), and lipid peroxides] were assayed using commercially available kits and correlated with the coronary artery lesion severity, assessed by the SYNTAX score (SS). The ROC curve assessed the biomarker potential of CRP, TNF-a, IL-10, and the TNF-a/IL-10 ratio to discriminate patients from healthy controls.

Results: In our study, we found that serum CRP (38.7 ± 1.9 versus 0.8 ± 0.04 mg/L; P < 0.001), TNF-a (68.4 ± 4.7 pg/mL versus 10.8 ± 0.7 pg/mL; P < 0.001), IL-10 (11.9 ± 0.8 pg/mL versus 8.7 ± 0.4 pg/mL; P = 0.001), and TNF-a/IL-10 ratio (6.8 ± 0.5 versus 1.7 ± 0.2; P < 0.001) were significantly higher in patients compared to healthy controls. Regarding oxidative stress markers, serum T-AOC levels (25.5 ± 0.9 versus 14.9 ± 0.4 U/mL; P < 0.001), NO (10.5 ± 0.3 versus 8.1 ± 0.3 nmol/mL; P < 0.001), serum LPO levels (15.8 ± 0.4 versus 4.1 ±0.2 mmol/L; P < 0.001) and lower GSH levels (3.8 ± 0.1 mg/mL versus 5.2 ± 0.2; P < 0.001) were significantly different in patients versus controls. CRP, TNF-a, and NO levels have been significantly correlated with the severity of CAD as assessed by the SYNTAX score.

Conclusion: Inflammation and oxidative stress are pathogenically implicated in premature STEMI and correlated with the severity of CAD lesions. The investigated biomarkers can be utilized in risk stratification and are theranostically targetable.