Plasmodium vivax is the second most common Plasmodium parasite causing clinically serious symptoms and death from malaria. It is an important cause of morbidity and mortality, especially in Asia, the Middle East, and South America. Human leukocyte antigen molecules are responsible for presenting foreign antigens to T cells. Polymorphisms in HLA genes affect antigen presentation. HLA alleles involved in the presentation of P. vivax antigens affect the antibody response. The present study aimed to reveal the relationship of rs3077 and rs9277535 polymorphisms in HLA-DP genes with malaria caused by P. vivax for the first time in the worldwide. In the present research, rs3077 and rs9277535 polymorphisms were investigated in a case–control study of 124 patients with P. vivax-induced malaria and 211 healthy persons by using a real-time polymerase chain reaction (RT-PCR). The results showed that the G alleles of rs3077 and rs9277535 polymorphisms were detected as protective alleles, while the A alleles of both polymorphisms increase the risk of susceptibility to malaria disease. The results of the present study showed that both polymorphisms have a major effect on the susceptibility to malaria caused by P. vivax. We recommend that this study should be conducted in a different population with a larger sample size to confirm our results. [ABSTRACT FROM AUTHOR]
This article discusses a rare case of secondary histiocytic sarcoma (HS) that developed rapidly following chimeric antigen receptor T-cell (CAR-T) therapy for relapsed diffuse large B-cell lymphoma (DLBCL). The patient initially presented with DLBCL and underwent various treatments, including CAR-T therapy, which resulted in a partial remission. However, PET/CT scans later revealed progression of the disease, and biopsies confirmed the presence of HS. Genetic testing showed a clonal relationship between the DLBCL and HS, supporting the hypothesis of divergent evolution. The article suggests that CAR-T therapy may have played a role in the development of HS, although further research is needed to confirm this. [Extracted from the article]
Bhattacharjee, Paromita, Sarkar, Paromita, and Bhadra, Kakali
Subjects
*ALKALOIDS, *ANTINEOPLASTIC agents, *APOPTOSIS, *CELLULAR signal transduction, *BIOLOGICAL products, *IMMUNODIAGNOSIS, *PHYTOCHEMICALS, *CYTOTOXINS, *CELL lines, *NUCLEIC acids, *MOLECULAR structure, *SPECTRUM analysis, *GENETICS, *CELL surface antigens, THERAPEUTIC use of alkaloids
Abstract
Use of small molecules as valuable drugs against diseases is still an indefinable purpose due to the lack of in-detail knowledge regarding proper bio-target identification, specificity aspects, mode-mechanism of binding and proper in vitro study. Harmaline, an important beta-carboline alkaloid, shows effective anti-proliferative action against different types of human cancers and is also found to be a nucleic acid targeting natural molecule. This review sought to address the different signal pathways of apoptosis by harmaline in different cancer cell lines and simultaneously to characterize the structure activity aspects of the alkaloid with different motifs of nucleic acid to show its preference, biological efficacy and genotoxicity. The results open up new insights for the design and development of small molecule-based nucleic acid therapeutic agents. [ABSTRACT FROM AUTHOR]
Based on the One Strain-Many Compounds (OSMAC) strategy, the secondary metabolites of Phomopsis lithocarpus FS508 were investigated. As a result, a new secondary metabolite, 4-methoxy-3-[4-(acetyloxy)-3-methyl-2-butenyl]benzoic acid (1) as well as eleven known compounds were isolated from the fermentation product of the strain FS508. Their structures were determined by NMR, IR, UV, and MS spectroscopic data analyses. All the isolated compounds were evaluated for cytotoxic and anti-inflammatory activities. Among them, compounds 3 and 9 displayed potent cytotoxicity against HepG-2 cell line, and compounds 2, 3 and 12 showed significant anti-inflammatory activities. [ABSTRACT FROM AUTHOR]
Fourteen diphyllin 4-C-substituted alkylide derivatives were designed and synthesized using a Heck coupling and subsequent hydrogenation reaction. Olefins 3g and 3i exhibited the highest cytotoxicity on breast cancer cell lines MCF-7 with IC50 values of 0.08 and 0.07 µM, and they showed weaker V-ATPase inhibitory potency compared to diphyllin. [ABSTRACT FROM AUTHOR]
This study examined the saponin extracted from the roots of Andrographis paniculata for the phytochemical content and antimicrobial and anticancer effects. The phytochemicals present in the methanol and aqueous root extracts included alkaloids, tannins, flavonoids, phenolic compounds, saponins, glycosides, steroids, triterpenoids, tannins, proteins, steroids, chlorogenics and carbohydrates. A. paniculata root saponin expressed antibacterial properties against four Gram-negative bacteria (Escherichia coli, Salmonella typhi, Proteus vulgaris, and Klebsiella pneumoniae), four Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, and Micrococcus luteus), and two fungi (Aspergillus niger and Candida albicans); the saponin also inhibited the proliferation of HePG2 cells, with an IC50 value of 125 µg mL−1. [ABSTRACT FROM AUTHOR]
Combination therapy at appropriately suitable doses presents a promising alternative to monotherapeutic drugs. In this study, Cinnamomum verum and Syzygium aromaticum essential oils and their major compounds have exhibited substantial leishmaniacidal potential against both promastigote and amastigote forms of Leishmania (L.) major. However, they displayed high cytotoxicity against Raw264.7 macrophage cells. Interestingly, when combined with each other or with amphotericin B, they demonstrated a synergistic effect (FIC<0.5) with low cytotoxicity. These combinations are able to modulate the production of nitric oxide (NO) by macrophages. Notably, the combination of S. aromaticum Essential oil with amphotericin B stimulates macrophage cells by increasing NO production to eliminate leishmanial parasites. Furthermore, investigation of the molecular mechanism of action of these synergistic combinations reveals potent inhibition of the sterol pathway through the inhibition of the CYP51 gene expression. The findings suggest that combination therapy may offer significant therapeutic benefits in both food and pharmaceutical fields. [ABSTRACT FROM AUTHOR]
Anterior uveitis is the most common anatomical type of uveitis. Patients with noninfectious anterior uveitis may develop various ocular complications and eventually visual impairment. Appropriately differentiating the etiologies can help clinicians to predict the outcome, arrange clinical follow-up, and decide the treatment or prevention strategy. Adequate treatment and effective prevention strategies can reduce the frequency of recurrence and the risk of developing complications. Human leukocyte antigen (HLA)-B27 is the most common positive finding in patients with noninfectious AAU in many countries including Taiwan. To report a consensus from experienced uveitis specialists and rheumatologists was made in Taiwan. A panel of nine ophthalmologists from nine different referral centers with expertise in the management of uveitis and an experienced rheumatologist was held on January 16, 2022. A comprehensive literature review was performed. Differential diagnoses for etiologies, general treatments, and prevention strategies were discussed. Each statement in the consensus was made only if more than 70% of the experts agreed. A flow chart and seven statements regarding the differential diagnoses for etiologies, treatments and preventions, and co-management with rheumatologists were included in the consensus. This article discusses the general diagnosis, treatment, and prevention of noninfectious acute anterior uveitis, with or without HLA-B27, in adults for general ophthalmologists to improve overall outcomes of these patients [ABSTRACT FROM AUTHOR]
To report on the value of presence of pigmentation on central anterior lens capsule (PioLe) in HLA B27- associated anterior uveitis (HLA B27-AU). 268 patients (320 eyes) with AU were reviewed. Two diagnostic models to predict probability of HLA-B27-AU were developed. The first model included 6 variables (age, gender, unilaterality, presence of non-granulomatous keratic precipitates, hypopyon, and intraocular pressure (IOP). The second model was developed to investigate the added value of PioLe into the first model. Unilaterality, presence of hypopyon, IOP <21 mmHg and PioLe were characteristic for HLA-B27 positive patients (P≤0.003 for all). All of 6 variables had area under receiver operating characteristic curves (AuROC) ≤ 60, but PioLe reached even higher value (65.5). Diagnostic model I and II had AuROC 76.3% (95%CI, 68.4%-84.2%) and 80.0% (95%CI, 72.6%-87.5%), respectively. Unilaterality, hypopyon, IOP <21 mmHg and presence of PioLe are clinical signs suggesting HLA B27- AU. [ABSTRACT FROM AUTHOR]
The present research displays the green synthesis of stable silver nanoparticles (Ag-NPs) and copper oxide nanoparticles (CuO-NPs). The aqueous solution of Spirulina platensis (blue green algae) source was used as a reducing and capping agent and this study assessed the cytotoxicity of Ag- and CuO-NPs on three cancer cell cultures: A549 (lung cancer), HCT (human colon cancer), Hep2 (laryngeal carcinoma cancer) and normal cell (WISH). For NPs characterization, the UV/Vis spectroscopy was used where their formation and crystallinity were proven with $$\lambda $$ λ max values for Ag- and CuO-NPs of 425 and 234 nm, respectively. According to X-ray diffraction and transmission electron microscopy (TEM), Ag-NPs were spherical in shape (size 2.23–14.68 nm) and CuO-NPs were small (size 3.75–12.4 nm). Zeta potential analysis showed the particles potential, which was recorded by −14.95 ± 4.31 mV for Ag-NPs and −21.63 ± 4.90 mV for CuO-NPs. After that, Ag- and CuO-NPs were assessed for anticancer properties against A549, HCT, Hep2 and WISH. IC50 of Ag-NPs recorded 15.67, 12.94, 3.8 and 10.44 µg/ml for WISH, A549, HCT and Hep2, respectively. IC50 for CuO-NPs was recorded as 32.64, 54.59, 3.98 and 20.56 µg/ml for WISH, A549, HCT and Hep2 cells, respectively. Safety limits for WISH and A549 were achieved 98.64% by 2.44 µg/ml and 83.43% by 4.88 µg/ml of Ag-NPs, and it was found to be 97.94% by 2.44 µg/ml against HCT, while that for Hep2 is 95.9% by 2.44 µg/ml. Concerning the anticancer effect of CuO-NPs, the safety limit was recorded as 88.70% by 2.44 and 98.48% by 4.88 µg/ml against WISH and A549, while HCT reached 89.92% by 2.44 µg/ml and Hep2 was 83.33% by 4.88 µg/ml. Green nanotechnology applications such as Ag-NPs and CuO-NPs have numerous benefits of ecofriendliness and compatibility for biomedical applications such as anticancer effects against cancer cells. [ABSTRACT FROM AUTHOR]
Seven new pentasaccharides (1–7), rehmaglupentasaccharides A-G, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known verbascose (8) and stachyose (9) were also obtained in the current investigation, and the structure of stachyose was unequivocally defined using X-ray diffraction data. Compounds 1–9 were tested for their cytotoxicity against five human tumor cell lines, influence on dopamine receptor activation, and proliferation effects against Lactobacillus reuteri. [ABSTRACT FROM AUTHOR]
This study investigated how Radix Bupleuri-Radix Paeoniae Alba (BP) was active against hepatocellular carcinoma (HCC). Traditional Chinese medicine systems pharmacology (TCMSP) database was employed to determine the active ingredients of BP and potential targets against HCC. Molecular docking analysis verified the binding activity of PTEN with BP ingredients. H22 cells were used to establish an HCC model in male balb/c mice. Immunofluorescence staining, immunohistochemistry, flow cytometry, western blotting, enzyme-linked immunosorbent assay, and real-time quantitative PCR were used to study changes in proliferation, apoptosis, PTEN levels, inflammation, and T-cell differentiation in male balb/c mice. The major active ingredients in BP were found to be quercetin, kaempferol, isorhamnetin, stigmasterol, and beta-sitosterol. Molecular docking demonstrated that these five active BP ingredients formed a stable complex with PTEN. BP exhibited an anti-tumor effect in our HCC mouse model. BP was found to increase the CD8+ and IFN-γ+/CD4+ T cell levels while decreasing the PD-1+/CD8+ T and Treg cell levels in HCC mice. BP up-regulated the IL-6, IFN-γ, and TNF-α levels but down-regulated the IL-10 levels in HCC mice. After PTEN knockdown, BP-induced effects were abrogated. BP influenced the immune microenvironment through activation of the PTEN/PD-L1 axis, protecting against HCC. [ABSTRACT FROM AUTHOR]
A new disaccharide glycoside, franchoside A (1), and 17 known compounds were isolated from the tubers of Arisaema franchetianum Engler. The chemical structure of the previously undescribed compound 1 was elucidated on the basis of detailed spectroscopic analyses. Compounds 1, 2, 6, 10, 14 and 18 showed significant cytotoxic activities at varying IC50 values in the range of 4.0–10.6 μM against five cancer cell lines. Compounds 8, 10, 13 and 17 (10 μM) exhibited moderate anti-inflammatory activities by inhibiting the NF-κB signaling pathway and the release of NO from RAW264.7 macrophages induced by lipopolysaccharide (LPS), while compounds 1, 9, 14, 15 and 16 showed weak anti-inflammatory activities. [ABSTRACT FROM AUTHOR]
A new phenolic compound oleiphenol (1), and a new dihydrochalcone oleifechalcone (2) along with seven known compounds (3-9) were isolated from the fruit shell of Camellia oleifera Abel. The planar structures of compounds 1 and 2 were determined on the basis of extensive spectroscopic analyses (IR, UV, NMR, and HR-ESI-MS) and comparison with literature data. The absolute configurations of the new structures were determined by ECD calculations and chemical methods. In addition, compounds 1-9 underwent a series of pharmacological activity tests, including cytotoxic, anti-inflammatory, anti-RSV and antioxidant activities. [ABSTRACT FROM AUTHOR]
Four new 2-pyrone derivatives, two pairs of enantiomers, (±)-egypyrone A [(±)-1] and (±)-egypyrone B [(±)-2], together with a new benzophenone analogue, orbiophenone B (3), were isolated from the endophytic fungus Penicillium egyptiacum. The enantiomeric mixtures (±)-1 and (±)-2 were separated through chiral HPLC, respectively. Their structures were elucidated by extensive analysis of spectroscopic data and the absolute configuration was determined by comparing the optical rotation of structurally similar molecule. Subsequently, the cytotoxic activities of (±)-1, (±)-2, and 3 against the U87 cell line were tested and no activity was observed at a concentration of 10 µM. [ABSTRACT FROM AUTHOR]
The present study investigated five poultry flocks (size 142-600 birds) suspected of chicken infectious anemia (CIA) from Maharashtra, India. The necropsy of dead birds revealed severe atrophy of the thymus, gelatinization of bone marrow, subcutaneous hemorrhages, growth impairment, and severe anemia. Specific PCR targeting, 1390 bp fragment of the CIAV, VP1 gene was used in this study. Sequence analysis revealed that CIAV sequences of this study were grouped in genotype A. At the nucleotide level identity of 99.6% or more was seen between field sequences. At the amino acid level identity of 100% was seen between field sequences and NGP-1. Also, VP1 protein sequences of this study showed high identity with TJBD40, GD-K-12 strains from China and AB046590 strain from Japan. Further, the protein sequences of field CIAV had 0.7% to 2.5% divergence from VP1 sequences of vaccine strains. Antigenic epitopes of VP1 protein were predicted by SVMTriPtool and the field CIAV presented substitutions in two epitopes. To conclude, present study confirms the circulation of genotype A of CIAV in Maharashtra, India and predicted VP1 proteins of field CIAV revealed changes in two epitopes compared to vaccine strains. [ABSTRACT FROM AUTHOR]
Nanoparticle-based drug delivery systems have found extensive use in delivering oncology therapeutics; however, some delivery vehicles still exhibit rapid immune clearance, lack of biocompatibility and insufficient targeting. In recent years, bionanoparticles constructed from tumour cell membranes have gained momentum as tumour-targeting therapeutic agents. Cancer cell membrane-coated nanoparticles (CC MCNPs) typically consist of a drug-loaded nanoparticle core coated with cancer cell membrane. CC MCNPs retain homologous tumour cell surface antigens, receptors and proteins, and it has been shown that the modified nanoparticles exhibit better homologous targeting, immune escape and biocompatibility. CC MCNPs are now widely used in a variety of cancer treatments, including photothermal, photodynamic and sonodynamic therapies, chemotherapy, immunotherapy, chemodynamical therapy or other combination therapies. This article presents different therapeutic approaches using multimodal antitumour therapy--combination of two or more therapies that treat tumours synergistically--based on tumour cell membrane systems. The advantages of CC MCNPs in different cancer treatments in recent years are summarised, thus, providing new strategies for cancer treatment research. [ABSTRACT FROM AUTHOR]
Nanocarrier antigen-drug delivery system interacts specifically with immune cells and provides intelligent delivery modes to improve antigen delivery efficiency and facilitate immune progression. However, these nanoparticles often have weak adhesion to cells, followed by insufficient cell absorption, leading to a failed immune response. Inspired by the structure and function of viruses, virus-like mesoporous silica nanoparticles (VMSNs) were prepared by simulating the surface structure, centripetal-radialized spike structure and rough surface topology of the virus and co-acted with the toll-like receptor 7/8 agonist imiquimod (IMQ) and antigens oocyte albumin (OVA). Compared to the conventional spherical mesoporous silica nanoparticles (MSNs), VMSNs which was proven to be biocompatible in both cellular and in vivo level, had higher cell invasion ability and unique endocytosis pathway that was released from lysosomes and promoted antigen cross-expression. Furthermore, VMSNs effectively inhibited B16-OVA tumor growth by activating DCs maturation and increasing the proportion of CD8+ T cells. This work demonstrated that virus-like mesoporous silica nanoparticles co-supply OVA and IMQ, could induce potent tumor immune responses and inhibit tumor growth as a consequence of the surface spike structure induces a robust cellular immune response, and undoubtedly provided a good basis for further optimizing the nanovaccine delivery system. [ABSTRACT FROM AUTHOR]
*CENTRAL nervous system, *GENOTYPES, *HISTOCOMPATIBILITY class I antigens, *LYMPHOMAS, *KILLER cell receptors
Abstract
An effective salvage regimen for the reinduction of remission is lacking for refractory or relapsed primary central nervous system lymphoma (r/r PCNSL). This study aimed to evaluate the efficacy and safety of cytarabine plus temozolomide in treating r/r PCNSL and to explore the associated prognostic factors. A single-center retrospective cohort study was conducted to assess the efficacy and safety of cytarabine and temozolomide (AT) in r/r PCNSL patients. KIR and HLA genotyping was performed on peripheral blood samples. Thirty PCNSL patients receiving an AT regimen (cytarabine 3 g/m2 for 2 days combined with temozolomide 150 mg/m2 for 5 days) in our institution were analyzed. The median age was 65 years (range 25–79 years). A total of 43.4% of patients (13/30) achieved an overall response within a median follow-up of 16 months (95% confidence interval [CI]: 11–23 months). The median PFS and OS of the cohort were 1.5 months (95% CI: 1–4 months) and 19.5 months (95% CI: 11 months to not calculable), respectively. Patients harboring KIR3DL1/HLA-B genotypes predicting low affinity had a higher response rate (p = 0.042) and longer median PFS (3 months) than those with KIR3DL1/HLA-B genotypes predicting high affinity (1 month) (p = 0.0047). Cox regression analysis indicated that KIR/HLA-B genotypes were independently associated with PFS (p = 0.043). However, KIR/HLA-B genotypes had no impact on the OS of the cohort. The toxicity of AT treatment was mild and manageable. The AT regimen was well tolerated, and patients with specific KIR-HLA genotypes may benefit from this regimen. [ABSTRACT FROM AUTHOR]
Optimal post-remission treatment for individual favorable and intermediate risk acute myeloid leukemia (AML) patients has not yet been established. Human leukocyte antigen (HLA)-mismatched stem cell microtransplantation (MST), may improve outcomes and avoid graft-versus-host disease in patients with first complete remission of AML. We retrospectively analyzed the efficacy, safety, and survival of 63 patients with favorable- or intermediate-risk AML who received MST, autologous stem cell transplantation (ASCT), or cytarabine single agent (CSA) as post-remission treatment from January 2014 to August 2021. The neutrophil recovery time was shorter in the MST group than in the CSA group. The 2-year cumulative incidences of relapse in the MST, ASCT, and CSA groups were 27.27%, 29.41%, and 41.67%, respectively. During follow-up, 21 patients (33.30%) died of relapse, including six (9.52%), five (7.94%), and 10 (15.84%) in the MST, ASCT, and CSA groups, respectively. The estimated 2-year overall survival (OS) and relapse-free survival (RFS) were 62.20% vs. 50.00% (P = 0.101) and 57.10% vs. 50.00% (P = 0.136), in the >60 years MST and CSA groups (P = 0.101). The estimated 2-year OS was 100%, 66.20%, and 69.10% in the MST, ASCT, and CSA groups (MST vs CSA, P = 0.044), meanwhile, the estimated 2-year RFS was 100%, 65.40%, and 59.80% in patients ≤60 years. MST, ASCT, and CSA are acceptable post-remission treatments for patients with favorable- and intermediate-risk AML and may not only improve the prognosis of the elderly but also prolong the OS and RFS of favorable- or intermediate-risk patients ≤60 years. [ABSTRACT FROM AUTHOR]
Li, Yuyuan, Li, Chengyao, Zhang, Ling, Li, Jiao, Li, Qixin, Ouyang, Haining, Luo, Jiaona, Zhu, Linrui, and Cai, Kui
Subjects
*ERYTHROCYTES, *BLOOD group antigens, *DARATUMUMAB, *BLOOD groups, *DITHIOTHREITOL, *BLOOD group incompatibility
Abstract
Use red blood cell stabilizer to store the antibody screening and antibody identification reagent red blood cells (RBCs) treated with 0.01 mol/L DTT and investigate its value in the pre-transfusion examinations of patients treated with daratumumab. Determined the optimal incubation time for the 0.01 mol/L DTT-treated RBCs method by evaluating the effect of treatment at different time points. Added ID-CellStab to store DTT-treated RBCs, determined the maximum shelf life of reagent RBCs by monitoring the hemolysis index, and assessed changes in the antigenicity of blood group antigens on the surface of RBCs during storage with antibody reagents. A protocol for long-term storage of reagent red blood cells treated with the 0.01 mol/L DTT method was established. The optimal incubation time was 40-50 min. RBCs could be stored stably for 18 days after adding ID-CellStab. The protocol was able to eliminate pan-agglutination caused by daratumumab, with no significant changes in the antigens of most blood group systems, except for some attenuation of K antigen and Duffy blood group system antigens during the storage period. The storage protocol of reagent RBCs based on the 0.01 mol/L DTT method does not affect the detection of most blood group antibodies and retains a certain degree of detection ability for anti-K antibodies, allowing patients treated with daratumumab to quickly perform pre-transfusion examinations, making up for the shortcomings of currently commercial reagent RBCs. [ABSTRACT FROM AUTHOR]
van Osch, Thijs L. J., Steuten, Juulke, Nouta, Jan, Koeleman, Carolien A. M., Bentlage, Arthur E. H., Heidt, Sebastiaan, Mulder, Arend, Voorberg, Jan, van Ham, S. Marieke, Wuhrer, Manfred, Brinke, Anja ten, and Vidarsson, Gestur
Subjects
*HISTOCOMPATIBILITY class I antigens, *PHAGOCYTOSIS, *BLOOD platelets, *MACROPHAGES, *BLOOD platelet transfusion
Abstract
Immune-mediated platelet refractoriness (PR) remains a significant problem in the setting of platelet transfusion and is predominantly caused by the presence of alloantibodies directed against class I human leukocyte antigens (HLA). Opsonization of donor platelets with these alloantibodies can result in rapid clearance after transfusion via multiple mechanisms, including antibody dependent cellular phagocytosis (ADCP). Interestingly, not all alloimmunized patients develop PR to unmatched platelet transfusions, suggesting variation in HLA-specific IgG responses between patients. Previously, we observed that the glycosylation profile of anti-HLA antibodies was highly variable between PR patients, especially with respect to Fc galactosylation, sialylation and fucosylation. In the current study, we investigated the effect of different Fc glycosylation patterns, with known effects on complement deposition and FcyR binding, on phagocytosis of opsonized platelets by monocyte-derived human macrophages. We found that the phagocytosis of antibody- and complement-opsonized platelets, by monocyte derived M1 macrophages, was unaffected by these qualitative IgG-glycan differences. [ABSTRACT FROM AUTHOR]
Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially fatal disease for which rapid diagnosis is crucial for patient outcomes. Deficient activity (< 10%) of the liver enzyme, ADAMTS13, is the pathophysiological hallmark of TTP, and measurement of the enzyme activity can establish the diagnosis of TTP with high accuracy. Thus, along with the clinical history, appropriate laboratory assessment of a suspected case of TTP is essential for diagnosis and treatment. Here, we present a review of the available laboratory tests that can assist clinicians in establishing the diagnosis of TTP, with special focus on ADAMTS13 assays, including the measurement of the antigen and activity, and detection of autoantibodies to ADAMTS13. [ABSTRACT FROM AUTHOR]
Silva-Beltrán, Norma Patricia, Galvéz-Ruíz, Juan Carlos, Ikner, Luisa A., Umsza-Guez, Marcelo Andrés, de Paula Castro, Thiago Luiz, and Gerba, Charles P.
Propolis is a resinous substance collected by bees (Apis mellifera). It is used for its biological properties. This natural product is available as a safe therapeutic option. Herein, we report the antiviral effects of brown propolis extract from Mexico and green and red propolis extracts from Brazil, as well as their phenolic compounds (quercetin, caffeic acid, and rutin) in preventing infection of MRC-5 cells by HCoV-229E. Normal human fibroblast lung cells (MRC-5) were used to determine the cytotoxicity of the compounds. All samples studied showed antiviral activity. Green and brown propolis extracts, and quercetin exhibited the best EC50 values with values of 19.080, 11.240, and 77.208 µg/mL against HCoV-229E, respectively, and with TC50 of 62.19, 29.192, and 298 µg/mL on MRC-5 cells, respectively. These results are the first in vitro study of the effects of propolis on HCoV-229E and provide the basis for the development of natural formulations against other coronavirus strains. [ABSTRACT FROM AUTHOR]
Two new pregnane glycosides (1 and 2), together with four known ones (3– 6), were isolated from the roots of Cynanchum auriculatum Royle ex Wight (Asclepiadaceae). On the basis of detailed spectroscopic analysis and chemical method, the structures of new compounds were characterized to be metaplexigenin 3-O-β-D-cymaropyranosyl- (1→4)-α-L-diginopyranosyl-(1→4)-β-D-cymaropyranoside (1), metaplexigenin 3-O-α-L-diginopyranosyl-(1→4)-β-D-cymaropyranoside (2). All the isolated compounds (1–6) were tested for their in vitro inhibitory activity against the growth of human colon cancer cell lines HCT-116. Compounds 5 and 6 showed significant cytoxicities with IC50 values of 43.58 µM and 52.21 µM. [ABSTRACT FROM AUTHOR]
Previous studies confirm that aberrant expression of cytokeratin 19 fragment antigen 21-1 (cyfra-21-1) is highly correlated with non-small cell lung cancer (NSCLC). Herein, a proportional electrochemical immunosensor based upon a methylene blue/cadmium telluride/molybdic sulfide (MB/CdTe/MoS2) nanocomposite was successfully fabricated for detecting tumor marker cyfra-21-1. The result indicates that MB/CdTe/MoS2 modified on the surface of a glassy carbon electrode (GCE) supplies a large surface area for immobilizing primary antibodies (Ab1), ensuring high selectivity and sensitivity. To further amplify the sensitivity of the biosensor, ferrocenecarboxylic acid (Fc-COOH) linked with amino-functionalized secondary antibodies through amido bond (Ab2-Fc) as the "signal-on" probe and MB-modified with MoS2 with a large specific surface area as the "signal-off" probe increase the number of active sites for integration of Ab2-Fc/Ag/BSA/Ab1/MB/CdTe/MoS2/GCE electrode with the linker cyfra-21-1 (Ag). Meanwhile, CdTe accelerates the electron transfer and enhances the MB current, improving the sensitivity and detection limit. The presence of cyfra-21-1 led to both the decreasing response of MB and increasing current responses of Fc upon the electrode. Based upon this strategy, the determination of cyfra-21-1 was achieved in a linear range from 10 pg/mL to 10,000 ng/mL with the lowest detectable concentration of 10 pg/mL (signal-to-noise ratio of 3). The electrochemical immunosensor performs a sensitive determination of cyfra-21-1, possibly providing a practical strategy for the clinical analysis of lung cancer. [ABSTRACT FROM AUTHOR]
CD4+CD25+ FOXP3+ regulatory T cells (Tregs) represent a subpopulation of CD4+ T cells central for the suppression of physiological and pathological immune reactions. Although distinct cell surface antigens are expressed in regulatory T cells, those components are also present on the surface of activated CD4+CD25- FOXP3-T cells, thus making the discrimination between Tregs and conventional CD4+ T difficult and isolation of Tregs complex. Yet, the molecular components driving Tregs' function are still not fully characterized. Aiming at unraveling molecular components specifically marking Tregs, and upon using quantitative real-time PCR (qRT-PCR) followed by bioinformatics analysis, we identified, in this study, differential transcriptional profiles, in peripheral blood CD4 + CD25 + CD127low FOXP3+ Tregs versus CD4 + CD25-FOXP3- conventional T cells, for set of genes with distinct immunological roles. In conclusion, this study identifies some novel genes that appeared to be differentially transcribed in CD4+ Tregs versus conventional T cells. The identified genes could serve as novel molecular targets relevant to Tregs' function and isolation. [ABSTRACT FROM AUTHOR]
A novel electrochemical sensing platform based on Fe3O4-antibody conjugate was developed for the rapid and sensitive determination of Salmonella typhimurium antigen in model suspensions. The conjugates Fe3O4-antibody were synthesized via carbodiimide cross-linking and characterized by infrared spectroscopy and cyclic voltammetry. The electrochemical properties of Fe3O4 magnetic nanoparticles in water were investigated; the possible mechanism of direct electrochemical reduction was proposed and justified as an analytical signal. The design of an electrochemical sensing platform with magnetically controlled flows has been proposed. Under the most appropriate conditions, the developed portable device was provided the linear response as I (µA) = (7.20 ± 0.35) × (–lg CAg) − (23.77 ± 1.95) in the concentration range 1 × 10−7–1 × 10−4 mg/mL. The detection limit was 390 ng/mL and was comparable to other works. [ABSTRACT FROM AUTHOR]
Chemical investigation of roots of the plant, Rubia cordifolia Linn, led to the isolation of an undescribed anthraquinone, cordifoquinone R, determined as 1,2-dihydroxy-6-methoxyanthracene-9,10-dione (6) based on the 1D and 2D NMR analyses and HRESIMS. Ten other known compounds viz.1,4-dihydroxy-2-methoxyanthracene-9,10-dione (1), rubiadin (2), xanthopurpurin (3), 1-methoxy-3-hydroxy-2-carbomethoxy-9,10-anthraquinone (4), alizarin (5), β-sitosterol glucoside (7), scopoletin (8), oleanolic acid, (9), pomolic acid (10), queretaroic acid (11) were also isolated. Out of these compounds, 4, 10, and 11 are first reported from this plant species. Compounds 2, 3, 6, 7, and 10 showed activity in the range of 16-32 µg/ml against S. aureus ATCC 29213. [ABSTRACT FROM AUTHOR]
Rotaviruses are rising as zoonotic viruses worldwide, causing the lethal dehydrating diarrhea in children, piglets, and other livestock of economic importance. A simple, swift, cost-effective, highly specific, and sensitive antigen-capture enzyme–linked immunosorbent assay (AC-ELISA) was developed for detection of porcine rotavirus-A (PoRVA) by employing rabbit (capture antibody) and murine polyclonal antibodies (detector antibody) produced against VP6 of PoRVA (RVA/Pig-tc/CHN/TM-a/2009/G9P23). Reactivity of the both polyclonal antibodies was confirmed by using an indirect ELISA, western-blot analysis and indirect fluorescence assay against rVP6 protein and PoRVA. The detection limit of AC-ELISA was found 50 ng/ml of PoRVA protein. The relative sensitivity and specificity of this in-house AC-ELISA were evaluated for detection of PoRVA from 295 porcine diarrhea samples, and results were compared with that of RT-PCR and TaqMan RT-qPCR. The relative sensitivity and specificity of AC-ELISA compared with those of TaqMan RT-qPCR were found as 94.4 and 99.2%, respectively, with the strong agreement (κ −0.58) between these two techniques. Furthermore, AC-ELISA could not detect any cross-reactivity with porcine epidemic diarrhea virus, transmissible gastro-enteritis virus, pseudo rabies virus and porcine circovirus-2. This in-house AC-ELISA efficiently detected PoRVA from clinical samples, which suggests that this technique can be used for large-scale surveillance and timely detection of rotavirus infection in the porcine farms. In this study, we used a Chinese porcine rotavirus-A (PoRVA) strain containing the I5, a dominant VP6-genotype in pigs, for production of VP6 (most conserved) protein based polyclonal antibodies (pAb) in rabbits (as capture Ab) and mouse (as detector Ab) for development of simple, cost effective, highly specific and sensitive AC-ELISA for detection of PoRVA. Furthermore, there is no any previous published report on application of rabbit and mouse pAb against VP6 for developing an AC-ELISA against PoRVA. [ABSTRACT FROM AUTHOR]
Because of all above five patients were older than 65, the survival of the CD5-AML patients older than 65 (45cases) was analyzed, among 302 AML patients admitted to our hospital during the same time period as CD5 + AML patients. Then we compared the mortality and OS of CD5 + AML to CD5-AML patients, and thought that such CD5+ AML patients might have a poor prognosis, should be given special attention to treatment. Compared with CD5- elderly patients by chi-square test, CD5+ patients had significantly higher mortality than CD5- patients over 65 (80.0% (4/5) vs.33.3% (15/45), I p i < 0.001). 8.4
FAB classification based on morphology and histochemical stains
Phytochemical analyses of Swertia davidii Franch. extracts using column chromatography and semi-preparative HPLC were performed. Two novel phenolic glycosides named swertiosides A and B (compounds 1 and 2, respectively) were isolated and characterized. Four known phenolic glycosides were also extracted (compounds 3-6). The structural characteristics of these novel compounds were analyzed using 1D, 2D NMR, and HRMS. All six compounds have never been isolated from this particular plant species before this study. Subsequent assessment of bioactive properties suggested that compounds 1 and 2 exhibited moderate levels of cytotoxicity. [ABSTRACT FROM AUTHOR]
The B 2 Σ − − X 2 Π (0 − 1) band has been identified and measured in the laboratory spectrum of the CD molecule for the first time. The emission from the discharge was observed with a high accuracy dispersive optical spectroscopy technique using a plane-grating spectrograph and recorded by a photomultiplier tube. In total, 99 ro-vibronic frequencies were measured with an absolute accuracy of about ± 0.010 cm − 1 . In the following work, we present the results of the combined analysis of the current experimental data and the B 2 Σ − − X 2 Π (0−0) [Szajna et al., J. Mol. Spectrosc. 324, 48–52 (2016)] and D 2 Π i − B 2 Σ − (0−0) [Herzberg and Johns, Astrophys. J. 158, 399–417 (1969)] bands of CD. The resulting data, compared to those from the earlier measurements, present more accurate molecular constants for the v = 0 vibrational level of the B 2 Σ − and D 2 Π i states. The parameters of the Λ-doubling (p, q) of the D 2 Π i (v = 0) level were obtained for the first time. The current observations and analysis have become a basis to discuss the possible detection of the CD radical in the interstellar medium by the R 2 (0.5) , Q 2 (0.5) + Q R 12 (0.5) and P Q 12 (0.5) spectral lines of the B 2 Σ − − X 2 Π (0 − 0) band in the 3880 Å region. [ABSTRACT FROM AUTHOR]
A 51-year-old male had a history of well-controlled Graves' disease (GD) under regular follow-up, and thyroid eye disease (TED) with post bilateral orbital decompression. However, after COVID-19 vaccination, recrudescence of GD and moderate-to-severe TED were diagnosed by increased thyroxine levels and decreased thyrotropin levels in serum, and positive results of thyrotropin receptor antibody and thyroid peroxidase antibody. Weekly intravenous methylprednisolone was prescribed. Symptoms gradually improved accompanied with reduction in proptosis: 1.5 mm of the OD and 2.5 mm of the OS. Possible pathophysiological mechanisms discussed included molecular mimicry theory, autoimmune/inflammatory syndrome induced by adjuvants, and certain genetic predisposition of human leukocyte antigen. Physicians should remind patients to seek treatment if the symptoms and signs of TED recur following COVID-19 vaccination. [ABSTRACT FROM AUTHOR]
Laryngopharyngeal reflux (LPR) is a common worldwide disease. LPR symptoms may involve distant organs and tissues including the ocular surface with manifestations of a Dry Eye-like disease. We evaluated the concomitant involvement of the ocular surface in patients with LPR. We also defined the clinical signs and the roles of chemical and neuro-inflammatory mediators in the tears of LPR patients. Seventy-seven patients with LPR (mean age 65.8 ± 16.8 SD) and 25 healthy controls (mean age 56.5 ± 16.3 SD) were recruited from the otorhinolaryngology unit. Each subject was evaluated for the presence of concomitant ocular surface disease through clinical examination, including the measurement of tear break-up time (TBUT) and the Ocular Surface Disease Index (OSDI) questionnaire. Tears and conjunctival imprints were collected. The presence of pepsin in tears was detected by ELISA. HLA-DR in conjunctival imprints were imaged by immunofluorescence microscopy. RT-PCR quantified conjunctival mRNA transcripts of HLA-DR, IL-8, MUC5AC, NADPH, VIP, and NPY. Patients with LPR had significantly increased OSDI and reduced TBUT scores compared to control subjects (p < 0.05 each). Pepsin was detected in 51% of patient tears while it was not measurable in the controls (p < 0.01). Immunoreactivity for HLA-DR in the conjunctival impressions was greater than for the controls with an increased mRNA expression (p < 0.05). mRNA transcripts for IL-8, NADPH, and VIP were significantly increased in LPR patients (p < 0.05 each), but neither MUC5AC nor NPY was different from controls. LPR can adversely affect the ocular surface, leading to moderate signs and symptoms of dry eye. This study provides evidence that the presence of pepsin, HLA-DR immunoreactivity, and increased mRNA expression of neuro-inflammatory markers in the tears and conjunctival imprints of LPR patients suggests a potential link between LPR inflammation and ocular surface disease. [ABSTRACT FROM AUTHOR]
Witte, Hanno M., Riecke, Armin, Saeger, Wolfgang, Hackenbroch, Carsten, Mathieu, René, Mauer, Uwe Max, and Schulz, Chris
Subjects
*PITUITARY gland, *ANTIGENS, *OPERATIVE surgery, *METASTASIS, *BLEPHAROPTOSIS, TUMOR surgery
Abstract
We report the case of a 61-year-old male with spindle cell oncocytoma of the hypophysis. On presentation to the Department of Neurosurgery at the German Armed Forces Hospital of Ulm, the patient reported a history of several years of left sixth nerve palsy, right ptosis, increased sensitivity to light, and a bilateral retrobulbar pressure sensation. Pituitary function was normal. A chromophobe non-functioning pituitary adenoma was initially suspected. The diagnosis was established on the basis of examination at a histopathology reference laboratory using immunohistochemistry to identify cell surface markers. During two years of follow-up, there were two clinical recurrences requiring surgery. To our knowledge, this is the 35th documented case of spindle cell oncocytoma of the pituitary gland and the first that was immunohistochemically negative for epithelial membrane antigen (EMA) and S100; and the first that displayed haematogenous metastasis to the right sphenoparietal sinus. The three surgical procedures were associated with massive intraoperative bleeding and thus resulted in subtotal tumor resection. Following surgery for the recurrences, the patient underwent radiotherapy. [ABSTRACT FROM AUTHOR]
Whether polymorphic Human Leukocyte Antigen (HLA)-A, HLA-B and HLA-DRB1 alleles were associated with acute liver disease after hepatitis B virus (HBV) infections was investigated. In this study, from initially 100 participants in each group, HLA-A, HLA-B and HLA-DRB1 sequences were available from 86 acute hepatitis B (AHB) patients and from 84 HBV-resistant individuals (controls), using sequencing-based typing allele groups and alleles that exhibited differences in distribution between the case and control groups were subjected to chi-squared and logistic regression analyses to identify those associated with AHB. A dose response analysis was also performed on the effect of HLA-A*24:02 allele number on acute liver disease following HBV infection. The frequency distribution of HLA-B and HLA-DRB1 alleles in the control group were in Hardy-Weinberg Equilibrium (P >.05). HLA-A*24:02 (χ2 = 6.949, P =.008) occurred most frequently in the AHB and HLA-DRB1*12:02 (χ2 = 7.768, P =.005) in the control group. With adjustment for sex, the logistic regression model showed that the HLA-A*24:02 allele was significantly associated with AHB liver injury (P =.0326, OR = 2.270, 95% CI: 1.070–4.816), whereas the other HLA-A, HLA-B, and HLA-DRB1 alleles were not (P >.05). A linear response was observed for the association between HLA-A*24:02 allele number and acute liver disease after HBV infections (χ2 = 4.428, P =.025). The HLA-A*24:02 allele may influence the severity of the cellular response to HBV infection, increasing the elimination of HBV-infected hepatocytes. The HLA-A*24:02 allele may be a potential screening marker for identifying people or regional populations in China at higher risk of acute liver disease following HBV infection. [ABSTRACT FROM AUTHOR]
Chisocarpene A (1) is a new tirucallane-type triterpenoid together with odoratone (2) and 24-methylenecycloartanol (3), isolated from the stem bark of Chisocheton lasiocarpus. The chemical structures of compounds 1–3 were elucidated through a detailed analysis of their spectroscopic data (IR, MS, 1 D, and 2 D NMR). The isolated compounds were evaluated for cytotoxic activity against the MCF-7 breast cancer cell line using a resazurin-based assay. Compound 1 showed the most potent activity (IC50 26.56 ± 1.01 µM) and was two-fold more active than the positive control. [ABSTRACT FROM AUTHOR]
Brexucabtagene autoleucel is a chimeric anti CD19 antigen receptor T-cell therapy that allows durable responses in relapsed/refractory (R/R) mantle cell lymphoma (MCL). The present study compared the clinical and economic outcomes of R/R MCL patients (pre-exposed to ibrutinib and chemoimmunotherapy) treated with brexucabtagene autoleucel versus Rituximab, bendamustine, cytarabine (R-BAC) in the Italian Healthcare System. A partitioned-survival model extrapolated survival and healthcare costs of R/R MCL patients over a lifetime horizon. Discounted and quality-adjusted life expectancy (QALY) was 6.40 versus 1.20 for brexucabtagene autoleucel versus R-BAC and lifetime costs were €411,403 versus €74,415, respectively, which corresponds to a cost of €64,798 per QALY gained. The results were highly sensitive to brexucabtagene autoleucel acquisition cost and to assumptions on long-term survival, therefore the cost-effectiveness of brexucabtagene autoleucel for patients with R/R MCL requires validation with longer follow-up data and in specific risk subgroups. [ABSTRACT FROM AUTHOR]
Clonal evolution to secondary paroxysmal nocturnal hemoglobinuria (PNH) or myeloid neoplasia (MN) represents one of the long-term complications of patients with aplastic anemia (AA). The recent evidence in the field of immunology and the application of next-generation sequencing have shed light on the molecular underpinnings of these clonal complications, revealing clinical and molecular risk factors as well as potential immunological players. Particularly, whether MN evolution represents a failed tumor surveillance or a maladaptive recovery is still a matter of controversy in the field of bone marrow failure syndromes. However, recent studies have explored the precise dynamics of the immune-molecular forces governing such processes over time, generating knowledge useful for potential early therapeutic strategies. In this review, we will discuss the immune pathophysiology of AA and the emergence of clonal hematopoiesis with regard to the adaptive and maladaptive mechanisms at the basis of secondary evolution trajectories operating under the immune pressure. [ABSTRACT FROM AUTHOR]
*BLOOD proteins, *EGYPTIANS, *IMMUNOGLOBULINS, *SARS-CoV-2, *VIRAL antigens, *IMMUNOSPECIFICITY, *IMMUNOGLOBULIN M
Abstract
Several diagnostic measures have been employed to precisely detect the SARS-CoV-2 viral infection using viral antigens, nucleic acids, and other serological approaches. The sensitivity and specificity of the serological tests remain a challenging need. Here, we describe the detection of human anti-SARS-CoV-2 IgG and IgM antibodies qualitatively through two optimized in-house ELISA and lateral flow immunoassay. Both approaches are based on the prokaryotic expression of 50 kDa SARS-CoV-2 recombinant nucleocapsid protein. This SARS-CoV-2rN-6×His was used either to coat ELISA plates or to be conjugated to gold nanoparticles followed by colorimetric detection of bound human IgG or IgM. In the LFA, we show the optimization of nanoparticle size, protein-binding capacity, membrane treatment, and finally testing the potential capacity of using either the optimized ELISA or LFA in detecting antibodies raised against viral infection. Assessment of both methods was carried out using human sera-positive and negative SARS-CoV-2 antibodies. The ELISA and LFA tests showed 86%, 96.5% sensitivity, 92%, 93.75% specificity, 97%, 98.2% PPV, and 64%, 88.2% NPV, respectively. In conclusion, both approaches were able to successfully detect human antibodies against SARS-CoV-2 nucleocapsid protein. The importance of both protocols cannot be overstated in the detection and diagnosis of viral infections, especially in developing countries. [ABSTRACT FROM AUTHOR]
Two new polyketides, pholiotones B and C (1 and 2), and four known compounds, trichodermatide D (3), vermistatin (4), dehydroaltenuene A (5) and terpestacin (6) were isolated from the crude extract of Pholiota sp. Their structures were identified by NMR and MS spectroscopic data. The absolute configurations of compounds 1 and 2 were elucidated by modified Mosher's method, electronic circular dichroism (ECD) calculations and 13C NMR calculations as well as DP4+ probability analyses. All the compounds were evaluated for their antifungal and cytotoxicity. [ABSTRACT FROM AUTHOR]
Two new compounds verboncin A (1) and verboncin B (4) and 14 known compounds (2–3 and 5–16) were isolated from Verbena bonariensis, and these 14 compounds were first obtained from this plant. Their chemical structures were established by one and two-dimensional NMR and HRESIMS analysis and the results were compared with literature values. The absolute configuration of 1 was determined by calculating electronic circular dichroism (ECD). The cytotoxicity of some of the compounds against MCF-7, HCT-116, MDA-MB-231, and SW620 human cancer cell lines were evaluated, in which compound 4 showed negligible cytotoxic activity with an IC50 value of 68.08 ± 0.35 µM against the MCF-7 cell line. [ABSTRACT FROM AUTHOR]
A new cytotoxic alkaloid, named streptothiazolidine B (1), together with three known compounds (2-4), were isolated from Streptomyces violaceoruber. The structure of the undescribed compound was established using 1D and 2D NMR, and HRESIMS. Streptothiazolidine B was isolated and identified as an amide alkaloid with a unique thiazolidine side chain and its absolute configuration was determined by a combination of NOESY experiment and ECD analysis. Streptothiazolidine B exhibited significant cytotoxic activities against two human tumor cell lines, Li-7 and A2780, with IC50 values of 7.8, and 9.1 μM. Meanwhile, compound 4 showed obvious cytotoxic activities against four human tumor cell lines, THP-1, HT29, Li-7 and A2780, with IC50 values ranging from 3.1 to 10.2 μM. [ABSTRACT FROM AUTHOR]
Celiac disease (CD) is an autoimmune small bowel disease. Genetic susceptibility for CD is mainly determined by the human leukocyte antigen (HLA)-DQ haplotypes. The risk of CD conferred by HLA genotypes varies geographically and across populations, however, this has not yet been documented in Chinese patients with CD. To investigate the distribution of HLA-DQ and the related risks of CD development in Northwest China. A total of 75 CD patients and 300 healthy individuals were genotyped for HLA-DQ using the Illumina NextSeq, and the relative risks of the different genotypes were evaluated. In total, 68.00% of CD patients and 21.00% of controls carried HLA-DQ2.5 heterodimers (p < 0.001). We identified four CD risk gradients. Individuals carrying a double dose of DQB1*02 had the highest risk of developing CD (1:16); however, with heterozygosis (DQB1*02:02/DQB1*02:01) having the highest risk (1:9). HLA-DQ2.5 individuals with a single copy of HLA-DQB1*02, in either the cis or trans configuration, were at a medium risk (1:38). Non-DQ2.5 carriers of DQ8 or DQ2.2 were at low risk, while only carriers of DQ7.5 or DQX.5 were at very low risk. Patients with the HLA-DQ2.5 genotype had more severe mucosal damage compared with the HLA-DQ2.5 genotype negative CD patients (70.59% vs. 41.67%, p = 0.016). Genetic susceptibility to CD is highly prevalent in the Northwest Chinese population and the highest risk of developing CD was associated with the DQ2.5/DQ2.2 genotype. The DQ2.5 allele is involved in the severity of mucosal injury. [ABSTRACT FROM AUTHOR]
Inthanusorn, Wasawat, Rutnakornpituk, Metha, and Rutnakornpituk, Boonjira
Subjects
*MAGNETIC nanoparticles, *SULFONIC acids, *IMMUNOGLOBULINS, *ANTIGENS, *TRANSMISSION electron microscopy
Abstract
Magnetite nanoparticles (MNPs) grafted with poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) and their use as anionic nano-adsorbents for positively charged antibody were herein presented. PAMPS grafted on MNP surface provided good water dispersibility and high negatively charged surface for electrostatic adsorption with positively charged entities, and MNPs provided a good magnetic responsiveness to facilitate the separation process. From transmission electron microscopy results, the size of the nanoclusters ranged between 50 and 200 nm in diameter with ca. 50–150 particles/cluster. Degree of the negative charge of PAMPS-grafted MNPs increased when increasing pH of the dispersion, indicating the pH-responsive properties of the MNPs. These MNPs were successfully used as nano-adsorbents for adsorption with anti-rabbit IgG through ionic interaction between negative charge of PAMPS-grafted MNP and positive charge of the antibody. In addition, the MNPs also provided the reusable ability by adsorption-desorption cycling process with higher than 80% adsorption ability after five consecutive reusing cycles. These hybrid materials should be alternative nano-adsorbents for other positively charged entities with high adsorption efficiency and reusable supports in magnetic separation applications. [ABSTRACT FROM AUTHOR]
The high structural similarity between the Zika virus (ZIKV) and other flaviviruses, such as Dengue Virus (DENV), complicates the identification of the infecting virus due to the occurrence of cross-reactions in serological assays. This phenomenon has increased the demand for more specific antigens for immunodiagnostic applications. The present work aimed to identify specific regions of ZIKV and produce unique antigens through computational methods, molecular and microbiological techniques. Based on the computational analysis we successfully expressed two recombinant proteins derived from specific regions of the ZIKV. Through serological assays using characterized sera, we observed that the region 146–182 of ZIKV's E protein, expressed in tandem, was not reactive despite the predictive sensitivity and specificity observed by computer analyses. On the other hand, the non-denatured fraction 220–352 of ZIKV's NS1 showed greater specificity to IgG+ sera of ZIKV by dot blot and western blot, which highlights its properties as a possible tool in the diagnosis of ZIKV. These findings demonstrate that ZIKV NS1 fraction 220–352 is a potential tool that may be applied in the development of serological diagnosis. We also provided data that suggest the non-applicability of the region 146–182 of ZIKV's protein E in serological assays despite previous indications about its potential based on computational analysis. [ABSTRACT FROM AUTHOR]
Beauvercin H (1), a new cyclic hexadepsipeptide, and two known ones (2 and 3) were isolated from the EtOH extract of the solid culture of Fusarium sp. Their structures were elucidated by spectroscopic analysis, including extensive 1D and 2D NMR techniques, as well as comparison with literature values. Additionally, compounds 1–3 were tested for their cytotoxic activities. The results showed that all isolated compounds exhibited cytotoxic activities against five human cancer cell lines with IC50 values ranging from 1.379 to 13.12 μM. [ABSTRACT FROM AUTHOR]
(–)-5-Methylmellein (1) and its new dimer (2) were isolated from cultures of the basidiomycete Inonotus sinensis. Their structures were elucidated on the basis of extensive spectroscopic methods including UV, IR, HR-EI-MS, 1D NMR and 2D NMR. The structure of Compound 2 was determined by single-crystal X-ray crystallographic analysis. Compound 2 was tested for the cytotoxicities against five human cancer cell lines. [ABSTRACT FROM AUTHOR]
P-type atypical lymphocytes may play important roles in the aetiology and therapy of schizophrenia. However, there is merely a direct immunological characterisation of it. The aim of this study is to explore the surface antigens of these cells and their comparative ultrastructure in schizophrenia. We recruited 25 age-and gender-matched patients with unmedicated schizophrenia, other mental diseases and healthy individuals. Peripheral venous blood was smeared and stained. CD4+, CD8+ and CD19+ cell surface antigen- positive lymphocytes were purified using magnetic beads and prepared for light microscopy and electron microscopy. The percentages of P-type atypical lymphocytes (34.53% ± 9.92%) were significantly higher (p < 0.0001) in schizophrenia than that of other mental diseases (9.79% ± 3.45%). These cells could present CD4+, CD8+ and CD19+ surface antigens. Their relative ultrastructure differed from that of normal lymphocytes, especially in mitochondria, which showed abundant, aggregated and quite irregular mitochondria; for example, slight dilation of the foci, swelling, degeneration, and even cavity. P-type atypical lymphocytes could be found among CD4+, CD8+, and CD19 + lymphocytes with schizophrenia. Their abnormal ultrastructure of mitochondria implied that energy metabolism might play an important role in the aetiology of schizophrenia. [ABSTRACT FROM AUTHOR]