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Foods (Basel, Switzerland) Mar 2024Jiuqu is one of the important raw materials for brewing Chinese rice wine (Huangjiu), often known as the "bone of wine". In this study, the microbial community and...
Jiuqu is one of the important raw materials for brewing Chinese rice wine (Huangjiu), often known as the "bone of wine". In this study, the microbial community and flavor substances of Jiuqu made with different amounts of shiitake mushroom () were investigated through high-throughput sequencing technology and headspace gas chromatography-ion migration spectroscopy (HS-GC-IMS), using traditional wheat yeast as a control. The results showed that 1593 genera and 5507 species were identified among the four types of yeast, with and being the most dominant microorganisms at the genus level. Carbohydrate, coenzyme, and amino acid metabolism may be the main metabolic processes of the dominant microorganisms in Jiuqu. In terms of flavor, a total of 79 volatile substance monomers and some dimers were detected from four types of Jiuqu raw materials, with the main substances being 12 aldehydes, 19 ketones, 13 alcohols, 19 esters, 4 olefins, 1 acid, 3 ethers, 4 furans, 1 pyrazine, 1 pyridine, 1 triethylamine, and 1 thiazole. The correlation results indicate that , , and correlate significantly with the volatile flavor compounds unique to shiitake mushrooms and also have a positive effect on alcohol, esters, and furans. These results could shed light on the selection of as a fermentation starter for Huangjiu in the Qinba Mountain area.
PubMed: 38611324
DOI: 10.3390/foods13071019 -
Blood Advances Jun 2024The efficacy and safety of acalabrutinib plus obinutuzumab and acalabrutinib monotherapy vs zanubrutinib in patients with treatment-naive chronic lymphocytic... (Comparative Study)
Comparative Study
The efficacy and safety of acalabrutinib plus obinutuzumab and acalabrutinib monotherapy vs zanubrutinib in patients with treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma without del(17p) were compared using an unanchored matching-adjusted indirect comparison. Individual patient-level data from ELEVATE-TN (acalabrutinib plus obinutuzumab, n = 162; acalabrutinib monotherapy, n = 163) were weighted to match published aggregate baseline data from SEQUOIA cohort 1, which excluded patients with del(17p) (zanubrutinib, n = 241), using variables that were prognostic/predictive of investigator-assessed progression-free survival (INV-PFS) in an exploratory Cox regression analysis of ELEVATE-TN. After matching, INV-PFS was longer with acalabrutinib plus obinutuzumab (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.23-0.74) and comparable with acalabrutinib monotherapy (HR, 0.91; 95% CI, 0.53-1.56) vs zanubrutinib. Acalabrutinib monotherapy had significantly lower odds of any grade hypertension vs zanubrutinib (odds ratio [OR], 0.44; 95% CI, 0.20-0.99), whereas acalabrutinib plus obinutuzumab had significantly higher odds of neutropenia (OR, 2.19; 95% CI, 1.33-3.60) and arthralgia (OR, 2.33; 95% CI, 1.37-3.96) vs zanubrutinib. No other significant differences in safety were observed. In summary, acalabrutinib plus obinutuzumab had longer INV-PFS with increased odds of neutropenia and arthralgia than zanubrutinib, whereas acalabrutinib monotherapy had similar INV-PFS with lower odds of any grade hypertension. These trials were registered at www.ClinicalTrials.gov as #NCT02475681 and #NCT03336333.
Topics: Humans; Benzamides; Antibodies, Monoclonal, Humanized; Pyrazines; Female; Male; Aged; Pyrimidines; Pyrazoles; Middle Aged; Leukemia, Lymphocytic, Chronic, B-Cell; Antineoplastic Combined Chemotherapy Protocols; Aged, 80 and over; Treatment Outcome; Piperidines
PubMed: 38598745
DOI: 10.1182/bloodadvances.2023012142 -
Leukemia Jun 2024
Topics: Humans; Bortezomib; Dexamethasone; Cyclophosphamide; Immunoglobulin Light-chain Amyloidosis; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Male; Female; Aged; Treatment Failure; Middle Aged
PubMed: 38594348
DOI: 10.1038/s41375-024-02243-5 -
Blood Cancer Journal Apr 2024
Topics: Humans; Multiple Myeloma; Hematopoietic Stem Cell Transplantation; Induction Chemotherapy; Transplantation, Autologous; Bortezomib; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Stem Cell Transplantation
PubMed: 38594252
DOI: 10.1038/s41408-024-01047-1 -
Journal of Oleo Science May 2024Gas chromatography-olfactory-mass spectrometry (GC-O-MS) combined with Aroma Extract Dilution Analysis (AEDA) were employed to characterize the key odor-active compounds...
Gas chromatography-olfactory-mass spectrometry (GC-O-MS) combined with Aroma Extract Dilution Analysis (AEDA) were employed to characterize the key odor-active compounds in sesame paste (SP) and dehulled sesame paste (DSP). The AEDA results revealed the presence of 32 and 22 odor-active compounds in SP and DSP, respectively. Furthermore, 13 aroma compounds with FD ≥ 2, OAV ≥ 1, and VIP ≥ 1 were identified as key differential aroma compounds between SP and DSP. Specifically, compounds such as 3-methylbutyraldehyde (OAV = 100.70-442.57; fruity), 2-methylbutyraldehyde (OAV = 106.89-170.31; almond), m-xylene (FD = 16; salty pastry), and 2,5-dimethylpyrazine (FD = 8-16; roasted, salty pastry) played an important role in this differentiation. Additionally, the dehulling process led to increased fermented, sweet, green, and nutty aroma notes in DSP compared to the more pronounced burnt and roasted sesame aroma notes in SP. Our findings offer a theoretical foundation for the regulation of sesame paste aroma profiles.
Topics: Sesamum; Odorants; Gas Chromatography-Mass Spectrometry; Food Handling; Pyrazines; Xylenes; Aldehydes; Taste; Flavoring Agents; Volatile Organic Compounds
PubMed: 38583980
DOI: 10.5650/jos.ess23253 -
Medicine Apr 2024Megalosplenia in newly diagnosed multiple myeloma (MM) is extremely rare, posing diagnostic and therapeutic challenges due to its unusual location and clinical... (Review)
Review
INTRODUCTION
Megalosplenia in newly diagnosed multiple myeloma (MM) is extremely rare, posing diagnostic and therapeutic challenges due to its unusual location and clinical manifestations and lack of optimal therapeutic strategies.
CASE PRESENTATION
A 65-year-old female who was previously healthy presented with a history of ecchymosis on her right leg accompanied by progressive fatigue for 2 weeks. She was admitted to our center in July 2019 due to thrombocytopenia. The patient presented with megalosplenia, anemia, monoclonal protein (λ-light chain type) in the serum and urine, and 45.6% malignant plasma cells in the bone marrow. Splenectomy was performed due to persistent splenomegaly after 3 cycles of the bortezomib plus dexamethasone regimen, and immunohistochemistry results indicated λ-plasmacytoma of the spleen. The same cytogenetic and molecular abnormalities, including t(14;16), 14q32 amplification, 16q32 amplification, 20q12 amplification, and a novel CYLD gene mutation, were identified using fluorescence in situ hybridization and next-generation sequencing in both bone marrow and spleen samples. Therefore, a diagnosis of MM (λ-light chain type, DS III, ISS III, R-ISS III, high-risk) with spleen infiltration was proposed. The patient did not achieve remission after induction treatment with bortezomib plus lenalidomide and dexamethasone or salvage therapy with daratumumab plus ixazomib and dexamethasone. However, she ultimately did achieve very good partial remission with a regimen of bendamustine plus lenalidomide and dexamethasone. Unfortunately, she died of pneumonia associated with chemotherapy.
CONCLUSION
To our knowledge, only 8 cases of spleen plasmacytoma at MM diagnosis have been described previously. Extramedullary myeloma patients with spleen involvement at diagnosis are younger and that the condition is usually accompanied by splenic rupture with aggressive clinical features and poor prognosis. Further studies are needed to explore pathogenesis and effective therapies to prolong the survival of such patients.
Topics: Humans; Female; Aged; Multiple Myeloma; Lenalidomide; Bortezomib; Plasmacytoma; In Situ Hybridization, Fluorescence; Dexamethasone; Mutation; Antineoplastic Combined Chemotherapy Protocols; Deubiquitinating Enzyme CYLD
PubMed: 38579060
DOI: 10.1097/MD.0000000000037624 -
Acta Dermato-venereologica Apr 2024Drug-associated bullous pemphigoid has been shown to follow long-term gliptin (dipeptidyl-peptidase 4 inhibitors) intake. This study aimed at identifying risk factors...
Drug-associated bullous pemphigoid has been shown to follow long-term gliptin (dipeptidyl-peptidase 4 inhibitors) intake. This study aimed at identifying risk factors for gliptin-associated bullous pemphigoid among patients with type 2 diabetes. A retrospective study was conducted in a tertiary centre among diabetic patients exposed to gliptins between the years 2008-2021. Data including demographics, comorbidities, medications, and laboratory results were collected using the MDClone platform. Seventy-six patients with type 2 diabetes treated with dipeptidyl-peptidase 4 inhibitors who subsequently developed bullous pemphigoid were compared with a cohort of 8,060 diabetic patients exposed to dipeptidyl-peptidase 4 inhibitors who did not develop bullous pemphigoid. Based on a multivariable analysis adjusted for age and other covariates, Alzheimer's disease and other dementias were significantly more prevalent in patients with bullous pemphigoid (p = 0.0013). Concomitant use of either thiazide or loop diuretics and gliptin therapy was associated with drug-associated bullous pemphigoid (p < 0.0001 for both). While compared with sitagliptin, exposure to linagliptin and vildagliptin were associated with bullous pemphigoid with an odds ratio of 5.68 and 6.61 (p < 0.0001 for both), respectively. These results suggest gliptins should be prescribed with caution to patients with type 2 diabetes with coexisting Alzheimer's and other dementias, or patients receiving long-term use of thiazides and loop diuretics. The use of sitagliptin over linagliptin and vildagliptin should be preferred in these patients.
Topics: Humans; Dipeptidyl-Peptidase IV Inhibitors; Vildagliptin; Pemphigoid, Bullous; Diabetes Mellitus, Type 2; Linagliptin; Retrospective Studies; Sodium Potassium Chloride Symporter Inhibitors; Risk Factors; Sitagliptin Phosphate; Dementia
PubMed: 38576104
DOI: 10.2340/actadv.v104.26663 -
Journal of Infection and Public Health May 2024The efficacy of the viral clearance and clinical outcomes of favipiravir (FPV) in outpatients being treated for coronavirus disease 2019 (COVID-19) is unclear.... (Randomized Controlled Trial)
Randomized Controlled Trial
A randomized trial to assess the acceleration of viral clearance by the combination Favipiravir/Ivermectin/Niclosamide in mild-to-moderate COVID-19 adult patients (FINCOV).
BACKGROUND
The efficacy of the viral clearance and clinical outcomes of favipiravir (FPV) in outpatients being treated for coronavirus disease 2019 (COVID-19) is unclear. Ivermectin (IVM), niclosamide (NCL), and FPV demonstrated synergistic effects in vitro for exceed 78% inhibiting severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) replication.
METHODS
A phase 2, open-label, 1:1, randomized, controlled trial was conducted on Thai patients with mild-to-moderate COVID-19 who received either combination FPV/IVM/NCL therapy or FPV alone to assess the rate of viral clearance among individuals with mild-to-moderate COVID-19.
RESULTS
Sixty non-high-risk comorbid patients with mild-to-moderate COVID-19 were randomized; 30 received FPV/IVM/NCL, and 30 received FPV alone. Mixed-effects multiple linear regression analysis of the cycle threshold value from SARS-CoV-2 PCR demonstrated no statistically significant differences in viral clearance rates between the combined FPV/IVM/NCL therapy group and the FPV-alone group. World Health Organization Clinical Progression scores and symptomatic improvement did not differ between arms on days 3, 6, and 10, and no adverse events were reported. No patients required hospitalization, intensive care unit admission, or supplemental oxygen or died within 28 days. C-reactive protein on day 3 was lower in the FPV/IVM/NCL group.
CONCLUSION
Viral clearance rates did not differ significantly between the FPV/IVM/NCL combination therapy and FPV-alone groups of individuals with mild-to-moderate COVID-19, although the combined regimen demonstrated a synergistic effect in vitro. No discernible clinical benefit was observed. Further research is required to explore the potential benefits of FVP beyond its antiviral effects.
TRIAL REGISTRATION
TCTR20230403007, Registered 3 April 2023 - Retrospectively registered,https://trialsearch.who.int/Trial2.aspx?TrialID=TCTR20230403007.
Topics: Adult; Humans; COVID-19; SARS-CoV-2; Ivermectin; Niclosamide; Acceleration; Treatment Outcome; Antiviral Agents; Amides; Pyrazines
PubMed: 38569269
DOI: 10.1016/j.jiph.2024.03.030 -
RSC Advances Mar 2024Treatments of -(1-benzo[]imidazol-2-yl)pyrazine-2-carboxamide (HL) and -(benzo[]thiazol-2-yl)pyrazine-2-carboxamide carboxamide ligands (HL) with [Ru(-cymene)Cl] and...
Treatments of -(1-benzo[]imidazol-2-yl)pyrazine-2-carboxamide (HL) and -(benzo[]thiazol-2-yl)pyrazine-2-carboxamide carboxamide ligands (HL) with [Ru(-cymene)Cl] and [Ru(PPh)Cl] precursors afforded the respective Ru(ii) complexes [Ru(L)(-cymene)Cl] (Ru1), [Ru(L)(-cymene)Cl] (Ru2), [Ru(L)(PPh)Cl] (Ru3), and [Ru(L)(PPh)Cl] (Ru4). These complexes were characterized by NMR, FT-IR spectroscopies, mass spectrometry, elemental analyses, and crystal X-ray crystallography for Ru2. The molecular structure of complex Ru2 contains one mono-anionic bidentate bound ligand and display pseudo-octahedral piano stool geometry around the Ru(ii) atom. The interactions with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) were investigated by spectroscopic techniques. The experimental binding studies suggest that complexes Ru1-Ru4 interact with DNA, primarily through minor groove binding, as supported by molecular docking results. Additionally, these complexes exhibit strong quenching of the fluorescence of tryptophan residues in BSA, displaying static quenching. The cytotoxicity studies of compounds Ru1-Ru4 were assessed in cancer cell lines (A549, PC-3, HT-29, Caco-2, and HeLa), as well as a non-cancer line (KMST-6). Compounds Ru1 and Ru2 exhibited superior cytotoxicity compared to Ru3 and Ru4. The cytotoxicity and selectivity of compounds Ru1 and Ru2 against A549, PC-3, and Caco-2 cell lines surpassed that of cisplatin.
PubMed: 38567259
DOI: 10.1039/d4ra00525b -
Scientific Reports Apr 2024B-Myb has received considerable attention for its critical tumorigenic function of supporting DNA repair. However, its modulatory effects on chemotherapy and...
B-Myb has received considerable attention for its critical tumorigenic function of supporting DNA repair. However, its modulatory effects on chemotherapy and immunotherapy have rarely been reported in colorectal cancer. Bortezomib (BTZ) is a novel compound with chemotherapeutic and immunotherapeutic effects, but it fails to work in colorectal cancer with high B-Myb expression. The present study was designed to investigate whether B-Myb deletion in colorectal cancer could potentiate the immune efficacy of BTZ against colorectal cancer and to clarify the underlying mechanism. Stable B-Myb knockdown was induced in colorectal cancer cells, which increased apoptosis of the cancer cells relative to the control group in vitro and in vivo. We found that BTZ exhibited more favourable efficacy in B-Myb-defective colorectal cancer cells and tumor-bearing mice. BTZ treatment led to differential expression of genes enriched in the p53 signaling pathway promoted more powerful downstream DNA damage, and arrested cell cycle in B-Myb-defective colorectal cancer. In contrast, recovery of B-Myb in B-Myb-defective colorectal cancer cells abated BTZ-related DNA damage, cell cycle arrest, and anticancer efficacy. Moreover, BTZ promoted DNA damage-associated enhancement of immunogenicity, as indicated by potentiated expression of HMGB1 and HSP90 in B-Myb-defective cells, thereby driving M1 polarization of macrophages. Collectively, B-Myb deletion in colorectal cancer facilitates the immunogenic death of cancer cells, thereby further promoting the immune efficacy of BTZ by amplifying DNA damage. The present work provides an effective molecular target for colorectal cancer immunotherapy with BTZ.
Topics: Animals; Mice; Bortezomib; Antineoplastic Agents; Immunogenic Cell Death; Cell Line, Tumor; Colorectal Neoplasms; Apoptosis
PubMed: 38565963
DOI: 10.1038/s41598-024-58424-w