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International Journal of Molecular... Jun 2024Chloroquine (CQ) is a 4-aminoquinoline derivative largely employed in the management of malaria. CQ treatment exploits the drug's ability to cross the erythrocyte...
Chloroquine (CQ) is a 4-aminoquinoline derivative largely employed in the management of malaria. CQ treatment exploits the drug's ability to cross the erythrocyte membrane, inhibiting heme polymerase in malarial trophozoites. Accumulation of CQ prevents the conversion of heme to hemozoin, causing its toxic buildup, thus blocking the survival of Plasmodium parasites. Recently, it has been reported that CQ is able to exert antiviral properties, mainly against HIV and SARS-CoV-2. This renewed interest in CQ treatment has led to the development of new studies which aim to explore its side effects and long-term outcome. Our study focuses on the effects of CQ in non-parasitized red blood cells (RBCs), investigating hemoglobin (Hb) functionality, the anion exchanger 1 (AE1) or band 3 protein, caspase 3 and protein tyrosine phosphatase 1B (PTP-1B) activity, intra and extracellular ATP levels, and the oxidative state of RBCs. Interestingly, CQ influences the functionality of both Hb and AE1, the main RBC proteins, affecting the properties of Hb oxygen affinity by shifting the conformational structure of the molecule towards the R state. The influence of CQ on AE1 flux leads to a rate variation of anion exchange, which begins at a concentration of 2.5 μM and reaches its maximum effect at 20 µM. Moreover, a significant decrease in intra and extracellular ATP levels was observed in RBCs pre-treated with 10 µM CQ vs. erythrocytes under normal conditions. This effect is related to the PTP-1B activity which is reduced in RBCs incubated with CQ. Despite these metabolic alterations to RBCs caused by exposure to CQ, no signs of variations in oxidative state or caspase 3 activation were recorded. Our results highlight the antithetical effects of CQ on the functionality and metabolism of RBCs, and encourage the development of new research to better understand the multiple potentiality of the drug.
Topics: Erythrocytes; Humans; Chloroquine; Hemoglobins; Anion Exchange Protein 1, Erythrocyte; Adenosine Triphosphate; Antimalarials; Caspase 3
PubMed: 38928131
DOI: 10.3390/ijms25126424 -
Biomolecules Jun 2024In recent years, there has been growing interest in the development of metal-free, environmentally friendly, and cost-effective biopolymer-based piezoelectric strain...
In recent years, there has been growing interest in the development of metal-free, environmentally friendly, and cost-effective biopolymer-based piezoelectric strain sensors (bio-PSSs) for flexible applications. In this study, we have developed a bio-PSS based on pure deoxyribonucleic acid (DNA) and curcumin materials in a thin-film form and studied its strain-induced current-voltage characteristics based on piezoelectric phenomena. The bio-PSS exhibited flexibility under varying compressive and tensile loads. Notably, the sensor achieved a strain gauge factor of 407 at an applied compressive strain of -0.027%, which is 8.67 times greater than that of traditional metal strain gauges. Furthermore, the flexible bio-PSS demonstrated a rapid response under a compressive strain of -0.08%. Our findings suggest that the proposed flexible bio-PSS holds significant promise as a motion sensor, addressing the demand for environmentally safe, wearable, and flexible strain sensor applications.
Topics: Curcumin; DNA; Graphite; Biopolymers; Biosensing Techniques
PubMed: 38927101
DOI: 10.3390/biom14060698 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To analyze the efficacy and influencing factors of cyclosporine (CsA) alone in the treatment of children with acquired aplastic anemia (AA).
OBJECTIVE
To analyze the efficacy and influencing factors of cyclosporine (CsA) alone in the treatment of children with acquired aplastic anemia (AA).
METHODS
The clinical data of children diagnosed with AA and treated with CsA alone from January 1, 2016 to December 31, 2020 in the Children's Hospital of Chongqing Medical University were collected, and the efficacy and influencing factors of CsA treatment were evaluated.
RESULTS
Among the 119 patients, there were 62 male and 57 female, with a median age of 7 years and 1 month. There were 45 cases of very severe AA (VSAA), 47 cases of severe AA (SAA), and 27 cases of non-severe AA (NSAA). At 6 months after treatment, the efficacy of VSAA was lower than that of SAA and NSAA, and there was a statistical difference ( < 0.01). 6 cases died early, 16 cases relapsed, 2 cases progressed to AML and ALL. The results of univariate analysis showed that the high proportion of lymphocyte in the bone marrow at 6 months was an adverse factor for the efficacy of CsA, while high PLT count was a protective factor ( =0.008, =0.002). The ROC curve showed that the cut-off values of PLT count and the proportion of bone marrow lymphocyte at 6 months were 16.5×10 /L, 68.5%, respectively. Multivariate analysis showed that the high proportion of lymphocyte in bone marrow at 6 months was an independent adverse factor for IST ( =0.020, =0.062), and high PLT count was a protective factor ( =0.044, =1.038). At 3 months of treatment, CsA response and NSAA were the risk factor for recurrence ( =0.001, 0.031).
CONCLUSION
The efficacy of NSAA was higher than that of SAA and VSAA after 6 months of treatment with CsA alone. A high PLT count at the initial diagnosis was a good factor for the effectiveness of CsA, and a high proportion of bone marrow lymphocyte was an unfavorable factor. CsA response at 3 months and NSAA were risk factors for recurrence.
Topics: Humans; Anemia, Aplastic; Cyclosporine; Female; Male; Child; Treatment Outcome; Platelet Count; Immunosuppressive Agents; Child, Preschool; Adolescent; Bone Marrow
PubMed: 38926977
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.029 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To compare the prognostic value of two predictive models based on C-reactive protein (CRP) and albumin (ALB), namely the CRP to ALB ratio (CAR) and the Glasgow... (Comparative Study)
Comparative Study
OBJECTIVE
To compare the prognostic value of two predictive models based on C-reactive protein (CRP) and albumin (ALB), namely the CRP to ALB ratio (CAR) and the Glasgow prognostic score (GPS), in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL).
METHODS
The data of newly diagnosed DLBCL patients admitted to our center from May 2014 to January 2022 were reviewed. A total of 111 patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with detailed clinical, laboratory data and follow-up information were included. The receiver operating characteristic (ROC) curve was performed to evaluate the predictive value of pre-treatment CAR on disease progression and survival. Furthermore, the association between CAR and baseline clinical, laboratory characteristics of patients was evaluated, and progression-free survival (PFS) and overall survival (OS) were compared between different CAR and GPS subgroups. Finally, the univariate and multivariate COX propor-tional hazard regression models were used to analyze the factors affecting disease outcomes.
RESULTS
ROC curve showed that the area under the curve (AUC) of CAR predicting PFS and OS in DLBCL patients was 0.687 ( =0.002) and 0.695 ( =0.005), respectively, with the optimal cut-off value of 0.11 for both predicting PFS and OS. Compared with the lower CAR (<0.11) group, the higher CAR (≥0.11) group had more clinical risk factors, including age >60 years ( =0.025), ECOG score ≥2 ( =0.004), Lugano stage III-IV ( < 0.001), non-germinal center B-cell-like (non-GCB) subtype ( =0.035), elevated lactate dehydrogenase (LDH) ( < 0.001), extranodal involved site >1 ( =0.004) and IPI score >2 ( < 0.001). The interim response evaluation of patients showed that the overall response rate (ORR) and complete response rate (CRR) in the lower CAR group were both significantly better than those in the higher CAR group (ORR: 96.9% 80.0%, =0.035; CRR: 63.6% 32.5%, =0.008). With a median follow-up of 24 months, patients with lower CAR had significantly longer median PFS and OS than those with higher CAR (median PFS: not reached 67 months, =0.0026; median OS: not reached 67 months, =0.002), while there was no statistical difference in PFS ( =0.11) and OS ( =0.11) in patients with GPS of 0, 1, and 2. Multivariate Cox regression analysis indicated that only sex (male) and IPI score >2 were independent risk factors for both PFS and OS.
CONCLUSION
CAR is significantly correlated with disease progression and survival in DLBCL patients; And compared with GPS, CAR has more advantages in predicting disease outcomes in DLBCL patients.
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Prognosis; C-Reactive Protein; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Serum Albumin; Male; Female; Vincristine; Prednisone; Rituximab; Cyclophosphamide; Doxorubicin; Middle Aged
PubMed: 38926961
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.013 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To investigate the clinical efficacy and prognosis of Rituximab combined with DHAX and CHOP regimen in the first-line treatment of elderly patients with newly diagnosed...
OBJECTIVE
To investigate the clinical efficacy and prognosis of Rituximab combined with DHAX and CHOP regimen in the first-line treatment of elderly patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).
METHODS
A total of 36 elderly patients with DLBCL who were admitted and treated with 3 of more courses of treatment from August 2011 to August 2021 were retrospectively analyzed, and they were divided into rituximab±DHAX (R±DHAX) regimen group (18 cases) and rituximab±CHOP (R-CHOP) regimen group (18 cases) according to the treatment plan, and clinical features, efficacy and survival of the patients were observed.
RESULTS
Compared with R-CHOP group, patients of the R±DHAX group were older, and had worse performance status and higher IPI score, the differences between two groups in age, ECOG score and IPI score were statistically significant ( =0.005 =0.018, =0.035), but there were no significant differences beween two groups in gender, whether there were B symptoms, whether LDH was elevated, whether there was extranodal involvement, cell origin, bone marrow infiltration, and whether rituximab was combined ( =0.738, =1, =0.315, =0.305, =0.413, =0.177, =0.711, =0.229). The efficacy could be evaluated in 36 cases, including CR 14 (38.9%), PR 17 (47.2%), PD 5 (13.9%), and ORR of 86.1% (31/36). There were no statistically significant differences in CR[(27.8%(5/18) 50.0%(9/18); >0.05] and PR [44.4%(8/18) 50.0%(9/18); >0.05] of R±DHAX group and R-CHOP group, there was statistically significant difference in ORR[72.2%(13/18) 100.0%(18/18); =0.045] between two groups. The 1-year OS of R±DHAX group and R-CHOP group was (38.9±11.5%)% and (94.4±7.4%)%, respectively, 2-year OS was (16.7±8.8)% and (72.2±10.6)%, respectively, and the differences between two groups were statistically significant ( =0.001, =0.002). The median survival time in the R±DHAX group was 11 months(95% :8.9-13.1), and the median survival time in the R-CHOP group was not reached, and there was a statistically significant difference between the groups ( < 0.001).
CONCLUSION
For elderly DLBCL patients, R±DHAX may not be superior to R-CHOP in OS, and ECOG score, IPI score and age may affect the survival of elderly DLBCL patients. However, R±DHAX regimen is safe, tolerable and has a certain efficacy, which can be used as one of the clinical treatment options for elderly DLBCL.
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Rituximab; Aged; Cyclophosphamide; Vincristine; Prednisone; Doxorubicin; Prognosis; Male; Female; Cytarabine; Treatment Outcome
PubMed: 38926958
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.010 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To investigate the effectiveness, safety, and related prognostic factors of the treatment of follicular lymphoma (FL) with a regimen containing Bendamustine.
[The Reduction of CD4 T Lymphocytes after the Treatment of Follicular Lymphoma with the Bendamustine Containing Regimen May Predict the Occurrence of Infection and Efficacy].
OBJECTIVE
To investigate the effectiveness, safety, and related prognostic factors of the treatment of follicular lymphoma (FL) with a regimen containing Bendamustine.
METHODS
The clinical data of 129 FL patients who were treated with Bendamustine containing regimen were collected from January 1,2020 to October 30,2022 in the Hematology Department of Lianyungang Second People's Hospital and Jiangsu Provincial People's Hospital. The patients were divided into three groups: Bendamustine plus Rituximab (BR), Bendamustine plus Obinutuzumab (GB), Rituximab + Cyclophosphamide + Epirubicin / Doxorubicin + Vindesine + Prednisone (R-CHOP). The efficacy, safety and related prognostic factors of the treatment of FL with a regimen based on Bendamustine were retrospectively analyzed.
RESULTS
The ORR was 98% for the BR group, 94% for the GB group, and 72.3% for the R-CHOP group, while the CR rate was 61.2%,70% and 40.4%, respectively. The ORR and CR rates of the R-CHOP group were statistically different from those of the BR group and GB group ( < 0.05). The 3-year PFS rate of the BR group, GB group, and R-CHOP group was 89.6%, 90.9%, 48.9%, respectively. There was a statistically significant difference in 3-year PFS between the R-CHOP group, BR group, and GB group ( < 0.05), while there was no statistically significant difference in 3-year OS( >0.05). Hematological adverse reactions were mainly bone marrow suppression. Lymphocytes and CD4T lymphocytes decreased to the lowest level about 6 months after treatment, and the incidence of lymphopenia in BR group and GB group was higher than that in R-CHOP group, with a statistical difference ( < 0.05). The higher incidence of non-Hematological adverse reactions were pulmonary infection, EB virus infection, hepatitis B virus reactivation, and gastrointestinal reactions without statistical difference in 3 groups ( >0.05), and were all controllable. The Receiver operating characteristic of CD4T lymphocyte count showed that AUC of BR group was 0.802, and the critical value was 258/uL; AUC of GB group was 0.754 with a critical value of 322/uL.
CONCLUSION
The treatment of FL with the Bendamustine containing regimen has good efficacy and controllable adverse reactions, but lymphocytopenia was significant after treatment, and the curative efficacy in combination with various CD20 monoclonal antibodies was different. The lowest CD4T lymphocyte count can be used as a predictive factor for the occurrence of infection and efficacy of the Bendamustine containing regimen for FL.
Topics: Humans; Bendamustine Hydrochloride; Lymphoma, Follicular; Male; Female; Antineoplastic Combined Chemotherapy Protocols; Retrospective Studies; CD4-Positive T-Lymphocytes; Middle Aged; Rituximab; Doxorubicin; Cyclophosphamide; Prednisone; Adult; Prognosis; Infections; Treatment Outcome; Vincristine
PubMed: 38926957
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.009 -
BMJ Open Gastroenterology Jun 2024To estimate the strength of association between exposure to selected classes of prescribed medications and the risk of developing iron deficiency anaemia (IDA),...
OBJECTIVE
To estimate the strength of association between exposure to selected classes of prescribed medications and the risk of developing iron deficiency anaemia (IDA), specifically considering oral anticoagulants (OACs), antidepressants, antiplatelet agents, proton pump inhibitors (PPIs) and non-steroidal anti-inflammatories.
DESIGN
A case-control study involving the analysis of community repeat prescriptions among subjects referred with IDA, and unmatched controls referred as gastroenterology fast-tracks for other indications. Multivariable logistic regression modelling was used to calculate ORs for the association between IDA presentation and each medication class, adjusted for age, sex and coprescribing. For those classes showing significance, it was also used to calculate risk differences between those in the IDA group with or without haemorrhagic lesions on investigation.
RESULTS
A total of 1210 cases were analysed-409 in the IDA group, and 801 in the control group. Significant associations were identified between presentation with IDA and long-term exposure to PPIs (OR 3.29, 95% CI: 2.47 to 4.41, p<0.001) and to OACs (OR 2.04, 95% CI: 1.29 to 3.24, p=0.002). IDA was not associated with long-term exposure to any of the other three drug classes. In contrast to the relationship with PPIs, the association with OACs was primarily in the IDA sub-group with haemorrhagic lesions.
CONCLUSION
Long-term exposure to PPIs and OACs are independently associated with the risk of developing IDA. There are grounds for considering that these associations may be causal, though the underlying mechanisms probably differ.
Topics: Humans; Anemia, Iron-Deficiency; Case-Control Studies; Female; Male; Proton Pump Inhibitors; Middle Aged; Aged; Anticoagulants; Risk Factors; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Platelet Aggregation Inhibitors; Adult; Logistic Models; Aged, 80 and over
PubMed: 38926132
DOI: 10.1136/bmjgast-2023-001305 -
BMJ Case Reports Jun 2024Autoimmune haemolytic anaemia (AIHA), autoimmune destruction of erythrocytes is most commonly secondary to immunomodulated conditions. The association between AIHA and...
Autoimmune haemolytic anaemia (AIHA), autoimmune destruction of erythrocytes is most commonly secondary to immunomodulated conditions. The association between AIHA and inflammatory bowel disease (IBD) has been poorly investigated. We aim to report a case of AIHA in a patient with ulcerative colitis (UC) treated with vedolizumab.A case of a woman in her 30s with UC that after the initiation of vedolizumab developed severe anaemia. Due to the absence of visible blood losses and a positive Coombs direct test, the diagnosis of AIHA was established. The patient initially initiated prednisolone with no response. Rituximab had to be introduced. After a few days with this therapy, there was a clinical and analytical improvement.AIHA must be taken into account as a possible cause of anaemia in patients with IBD. The differential diagnosis between IBD or drug-related (namely vedolizumab) as the cause of the AIHA is complex and almost impossible to establish.
Topics: Humans; Colitis, Ulcerative; Antibodies, Monoclonal, Humanized; Female; Anemia, Hemolytic, Autoimmune; Adult; Rituximab; Gastrointestinal Agents; Immunologic Factors; Treatment Outcome
PubMed: 38926127
DOI: 10.1136/bcr-2024-260586 -
Discovery Medicine Jun 2024Cutaneous melanoma is a malignant tumor with an increasing incidence, prone to recurrence and metastasis. This study aims to explore the effects and mechanisms of the...
BACKGROUND
Cutaneous melanoma is a malignant tumor with an increasing incidence, prone to recurrence and metastasis. This study aims to explore the effects and mechanisms of the novel shikonin derivative 5,8-dimethyl alkannin oxime derivative (DMAKO-20) on the metastasis and invasion of melanoma cells.
METHODS
The inhibitory effects of DMAKO-20 on the melanoma cell line A375 were investigated through Cell Counting Kit-8 (CCK-8), Transwell and angiogenesis experiments. Network pharmacology and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to explore potential sites and pathways involved in this process. Additionally, quantitative polymerase chain reaction (qPCR) and Western blot experiments were conducted before and after drug treatment to verify the expression trends of related pathways and proteins.
RESULTS
DMAKO-20 demonstrated selective inhibition of proliferation, invasion and migration of melanoma cells at low concentrations. The WNT pathway appears to be implicated in this process, as DMAKO-20 effectively attenuates its activation, consequently reducing matrix metalloproteinase 9 (MMP9) and Cellular Communication Network Factor 1 (CCN1)/cysteine-rich angiogenic inducer 61 (CYR61) levels. Such modulation inhibits melanoma dissemination and invasion into other tissues.
CONCLUSION
DMAKO-20 exhibits the capability to suppress metastasis and invasion of melanoma cells, suggesting its potential for clinical application as an adjuvant therapy against melanoma.
Topics: Humans; Naphthoquinones; Melanoma; Cell Line, Tumor; Neoplasm Invasiveness; Cell Movement; Cell Proliferation; Neoplasm Metastasis; Wnt Signaling Pathway; Skin Neoplasms; Gene Expression Regulation, Neoplastic; Melanoma, Cutaneous Malignant
PubMed: 38926109
DOI: 10.24976/Discov.Med.202436185.113 -
Discovery Medicine Jun 2024Atypical acinar cell foci (AACF) seen in pancreatic cancer are fatal and have been studied with some causative agents. However, for the first time, the effect of...
BACKGROUND
Atypical acinar cell foci (AACF) seen in pancreatic cancer are fatal and have been studied with some causative agents. However, for the first time, the effect of acetylsalicylic acid with nitric oxide (NO-ASA) on AACF was examined in this study. Although NO-ASA has very successful inhibitory effects against some types of cancer, it has not been investigated whether they can exert their inhibition effects on AACFs.
METHODS
For experimental purposes, 21 14-day-old male Wistar albino rats were used. Azaserine (30 mg/kg) was dissolved in 0.9% NaCl solution and injected intraperitoneally (i.p.) into 14 rats, except for the Control group (Cont) rats, for three weeks. Rats that were injected with azaserine once a week for three weeks and those that did not receive treatment were divided into experimental groups. 15 days after the end of the azaserine injection protocol, NO-ASA was applied to azaserine with NO-ASA (Az+NO-ASA) group rats three consecutive times with an interval of 15 days by gavage. At the end of the 5-month period, pancreatic tissue was dissected and weighed. Pancreas preparations prepared from histological sections were examined for AACF burden and analyzed via a video image analyzer. One-way analysis of variance (ANOVA) non-parametric statistical analyses were performed to test whether there was a difference between the averages of the experimental and Control groups.
RESULTS
AACF burden in both groups injected with azaserine was found to be statistically significant in all categories compared to that of the Control group ( < 0.05). The average Calculated Estimated average AACF volume (mm) values, the Calculated estimated average AACF diameter (μm), the Estimated average number of AACF per unit volume, AACF rate as a % of Calculated Organ Volume were higher in the AzCont group rats than in the Az+NO-ASA group, when compared, and there was an important level statistical difference between the groups ( < 0.05). It was determined that for all parameters AACFs load in Az+NO-ASA group rats were significantly reduced compared to that of AzCont group rats ( < 0.05).
CONCLUSIONS
We observed that, as a result of the NO-ASA application, the experimental AACF focus ratio created by azaserine injection was significantly inhibited. The inhibitory effect of AACFs in Az+NO-ASA group rats may have resulted from the significant and independent chemopreventive and/or chemotherapeutic activity of NO-ASA against exocrine pancreatic AACF foci.
Topics: Animals; Male; Aspirin; Rats, Wistar; Nitric Oxide; Rats; Pancreatic Neoplasms; Acinar Cells; Pancreas, Exocrine
PubMed: 38926102
DOI: 10.24976/Discov.Med.202436185.106