Neutralizing chimeric heavy-chain antibody targeting the L-HN domain of Clostridium botulinum neurotoxin type F.

Botulinum toxin (BoNT) from Clostridium botulinum is the most toxic biotoxin known and is also an important bioterrorism agent. After poisoning, the only effective treatment is injection of antitoxin. However, neutralizing nanoantibodies are safer and more effective, representing a promising therapeutic approach. Therefore, it is important to obtain effective neutralizing nanoantibodies. Hence, the present study aimed to construct a phage antibody library by immunizing a camel and screening specific clones that bind to the L-HN domain of BoNT/F and constructing chimeric heavy-chain antibodies by fusing them with a human Fc fragment. The antibodies' affinity and in vivo neutralizing activities were evaluated. The results showed that 2 µg of F20 antibody could completely neutralize 20 × the median lethal dose (LD50) of BoNT/F in vitro. Injection of 5 mg/kg F20 at 1 h, 2 h, 3 h, and 4 h into mice after BoNT/F challenge resulted in complete survival in vivo. Overall, the antibody might be a candidate for the development of new drugs to treat botulism.

Multi-Omics Analysis Reveals the Role of Changes in Platelet Activation Pathways in the Survival Outcome of Patients with Esophageal Squamous Cell Carcinoma.

Objective: The objective of this study was to integrate metabolomics and transcriptomics data to identify key diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC). Plasma samples were collected from 85 ESCC patients at different stages and 50 healthy volunteers for non-targeted metabolomic analysis. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for non-targeted metabolomic analysis. Subsequently, we integrated the metabolomic data with transcriptomic data from the Gene Expression Omnibus (GEO) and prognosis data from The Cancer Genome Atlas Program (TCGA) to perform pathway analysis. Our focus was on pathways that involve both metabolites and upstream genes, as they often exhibit higher accuracy. Results: Through the integration of metabolomics and transcriptomics, we identified significant alterations in the platelet activation pathway in ESCC. This pathway involves the participation of both metabolites and genes, making it a more accurate reflection of pathological changes associated with the disease. Notably, metabolite arachidonic acid (AA) and chemokine receptor type 2(CXCR2) were significantly downregulated in ESCC, while genes collagen type I alpha 1(COL1A1), collagen type I alpha 2(COL1A2), collagen type III alpha 1(COL3A1), type 3 inositol 1,4,5-trisphosphate receptor (ITPR3), and insulin-like growth factor II mRNA binding protein 3(IGF2BP3) were significantly upregulated, indicating the presence of tumor-induced platelet activation in ESCC. Further analysis of prognosis data revealed that high expression of COL1A1, IGF2BP3, and ITPR3 was associated with a favorable prognosis for ESCC, while high CXCR2 expression was linked to an adverse prognosis. In addition, we combined COL1A1, ITPR3, IGF2BP3, CXCR2, and AA to form a diagnostic biomarker panel. The receiver operating characteristic curve (ROC) demonstrated excellent diagnostic capability (AUC=0.987). Conclusion: Our study underscores the significant role of platelet activation pathways and related genes in the diagnosis and prognosis of ESCC patients. These findings offer promising insights for improving the clinical management of ESCC.

Construction of scalable multi-channel DNA nanoplatform for the combined detection of ctDNA biomarkers of ovarian cancer.

Single-level biomarker detection has the limitation of insufficient accuracy in cancer diagnosis. Therefore, the strategy of developing highly sensitive, multi-channel biosensors for high-throughput ctDNA determination is critical to improve the accuracy of early diagnosis of clinical tumors. Herein, in order to achieve efficient detection of up to ten targets for early diagnosis of ovarian cancer, a DNA-nanoswitch-based multi-channel (DNA-NSMC) biosensor was built based on the multi-module catalytic hairpin assembly-mediated signal amplification (CHA) and toehold-mediated DNA strand displacement (TDSD) reaction. Only two different fluorescence signals were used as outputs, combined with modular segmentation strategy of DNA-nanoswitch-based reaction platform; the multi-channel detection of up to ten targets was successfully achieved for the first time. The experimental results suggest that the proposed biosensor is a promising tool for simultaneously detecting multiple biomarkers for the early diagnosis of ovarian cancer, offering new strategies for the early screening, diagnosis, and treatment not only for ovarian cancer but also for other cancers.

Efficacy of anti-programmed cell death protein 1 monoclonal antibody combined with bevacizumab and/or Pseudomonas aeruginosa injection in transplanted tumor of mouse forestomach carcinoma cell gastric cancer in mice and its mechanism in regulating tumor immune microenvironment.

Tumor immunotherapy represented by programmed cell death protein 1 (PD-1) inhibitors is considered as the most promising cancer treatment method and has been widely used in the treatment of advanced gastric cancer (GC). However, the effective rate of PD-1 inhibitor monotherapy is low. In this study, we constructed a transplanted tumor model in GC mice by inoculating mouse forestomach carcinoma cell (MFC) GC cells into 615 mice. Interventions were conducted with normal saline, anti-PD-1 monoclonal antibody (mAb), bevacizumab, Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA), anti-PD-1 mAb combined with bevacizumab, anti-PD-1 mAb combined with PA-MSHA, bevacizumab combined with PA-MSHA, anti-PD-1 mAb combined with bevacizumab and PA-MSHA, respectively. The tumor growth curves were drawn. TUNEL assay, western blotting, and immunohistochemistry were used to detect tumor proliferation and apoptosis. Flow cytometry and ELISA were used to detect the expression of tumor infiltrating lymphocytes and cytokines. This study found that anti-PD-1 mAb alone could not significantly inhibit the growth of transplanted tumors in mice. Anti-PD-1 mAb combined with bevacizumab, anti-PD-1 mAb combined with PA-MSHA, anti-PD-1 mAb combined with bevacizumab and PA-MSHA could all significantly inhibit tumor growth in mice, and the combination of three drugs presented the highest tumor inhibition rate. Anti-PD-1 mAb combined with bevacizumab and PA-MSHA could significantly upregulate the number of Th1-type cells, CD8 + T cells, and Type I tumor-associated macrophages (TAMs), while downregulate the number of Th2-type cells, myeloid-derived suppressor cells, regulatory T cells, and Type II TAMs. Therefore, we conclude that anti-PD-1 mAb combined with bevacizumab and/or PA-MSHA has a synergistic effect. Bevacizumab and PA-MSHA can transform the tumor immunosuppressive microenvironment into a supportive immune microenvironment, thus maximizing the antitumor effect of anti-PD-1 mAb.

Sulfation of hyperoside by the human cytosolic sulfotransferases (SULTs): impact of genetic polymorphisms on hyperoside-sulfating activity of SULT1C4 allozymes.

This study aimed to identify human cytosolic sulfotransferases (SULTs) that are capable of mediating hyperoside sulfation and examine the impact of genetic polymorphisms on their sulfating activity. Of the thirteen known human SULTs analyzed, five (1A1, 1A2, 1A3, 1C2, and 1C4) displayed sulfating activity toward hyperoside. Kinetic parameters of SULT1C4 that showed the strongest sulfating activity were determined. Ten SULT1C4 allozymes previously prepared were shown to display differential sulfating activities toward hyperoside, revealing clearly the functional impact of SULT1C4 genetic polymorphisms. These findings provided a robust biochemical foundation for further studies on the metabolism of hyperoside by sulfation.

The roles, controversies, and combination therapies of autophagy in lung cancer.

Lung cancer is one of the leading causes of death among men and women worldwide. The disease initially has a silent phenotype, which leads to the progression of the disease and ultimately the lack of proper response to routine treatments. Autophagy, known as an intracellular "recycle bin" for the degradation of defective proteins and molecules, is one of the mechanisms that has been considered in the context of cancer in recent years. This study aims to provide a comprehensive review of published articles on autophagy in the context of lung cancer to have a complete view of the role of autophagy in lung cancer and its possible treatments. PubMed, Scopus, and Google Scholar were searched until June 15 to find related articles. No specific search filters or restrictions were applied. The results were entered into reference management software for aggregation and management. The full text of all articles was screened and studied. In conclusion, studies on the exact function of autophagy in lung cancer are contradictory, but what can be concluded from a review of literature on lung cancer is that targeting autophagy combined with traditional routine therapies such as chemotherapy, especially in advanced stages of lung cancer, can be an effective anticancer approach.

Spatiotemporal dynamics and anthropologically dominated drivers of chlorophyll-a, TN and TP concentrations in the Pearl River Estuary based on retrieval algorithm and random forest regression.

Estimation of large-scale and high-precision water quality parameters is critical in explaining the spatiotemporal dynamics and the driving factors of water quality variability, especially in areas with environmental complexity (e.g., crisscrossing waterways, high flood risk in rainy season and seawater invasion). Thus, in this study, a retrieval algorithm was developed to predict chlorophyll-a (Chl-a), total nitrogen (TN) and total phosphorus (TP) concentrations in the Pearl River Estuary (PRE) based on a large amount of in situ measurements and Landsat 8 remote sensing images. Random Forest (RF) machine learning was conducted to identify the relationship between environmental indicators (pH, turbidity, conductivity, total dissolved solids and water temperature), Chl-a, TN and TP. The results showed that the NIR/R Binomial algorithm for Chl-a estimation presented appreciable reliability with R2 of 0.7429, root mean square error (RMSE) of 1.2089 and mean absolute percent error (MAPE) of 15.33%. The water quality variation in the PRE showed a characteristic of overall improvement and regional deterioration with average concentrations of 7.28 µg/L, 1.15 mg/L and 0.12 mg/L for Chl-a, TN, and TP respectively. Turbidity and pH were identified as the most important indicators to explain Chl-a (52.86%, 39.91%), TN (52.38%, 40.57%) and TP (55.23%, 40.03%) variation. Agricultural pollution was the main pollution source due to the intensive application of fertilizer and increased field size. Besides, land use patterns (e.g., increasing farmland but decreasing forest) greatly influenced water quality from 2010 to 2020. Moreover, light limitation caused by high turbidity reduced the algae productivity and further lowered the Chl-a concentration. The driving factors for regional water quality variations were anthropologically dominated and supplemented by climate change. This study improved the monitoring accuracy of regional water environment and provided quantitative early warning of water pollution events for environmental practitioners, so as to achieve long-term monitoring, precise pollution management and efficient water resources management.

Prognostic Value of Lateral Pelvic Lymph Node Dissection for Rectal Cancer: A Meta-Analysis.

BACKGROUND AND AIMS: The benefit of lateral pelvic lymph node dissection (LPLD) for locally advanced rectal cancer remains controversial. This meta-analysis aimed to evaluate the prognostic value of LPLD in patients with locally advanced rectal cancer. METHODS: We performed a systematic search in PubMed, Embase, and the Cochrane Library for publications comparing radical resection plus LPLD (LPLD group) with single radical resection (non-LPLD group) for locally advanced rectal cancer. A total of 15 studies satisfied our inclusion criteria and were assessed. Random-effects and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. RESULTS: LPLD significantly increased grade 3-4 postoperative complications (odds ratio [OR]1.44, 95% CI 1.03-2.02; P = 0.03) compared with non-LPLD. There were no significant differences in 5-y overall survival (hazard ratio = 0.90, 95% CI 0.77-1.05; P = 0.17), 5-y disease-free survival (hazard ratio 1.12, 95% CI 0.60-2.09; P = 0.73), local recurrence (OR 0.89, 95% CI 0.53-1.51; P = 0.68) or distant recurrence (OR 0.85, 95% CI 0.64-1.12; P = 0.24). CONCLUSIONS: We found that LPLD significantly increased grade 3-4 postoperative complications but did not increase 5-y overall survival or 5-y disease-free survival compared with single radical resection for locally advanced rectal cancer. Furthermore, it did not decrease the local recurrence or distant recurrence rates. Thus, more multicenter large-scale randomized controlled trials should be conducted to further explore whether the long-term survival benefits of LPLD truly exist.

Sulfation of Quercitrin, Epicatechin and Rutin by Human Cytosolic Sulfotransferases (SULTs): Differential Effects of SULT Genetic Polymorphisms.

Radix Bupleuri is one of the most widely used herbal medicines in China for the treatment of fever, pain, and/or chronic inflammation. Quercitrin, epicatechin, and rutin, the flavonoids present in Radix Bupleuri, have been reported to display anti-inflammatory, antitumor, and antioxidant biological activities among others. Sulfation has been reported to play an important role in the metabolism of flavonoids. In this study, we aimed to systematically identify the human cytosolic sulfotransferase enzymes that are capable of catalyzing the sulfation of quercitrin, epicatechin, and rutin. Of the thirteen known human cytosolic sulfotransferases, three (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1C2, and cytosolic sulfotransferase 1C4) displayed sulfating activity toward quercitrin, three (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1A3, and cytosolic sulfotransferase 1C4) displayed sulfating activity toward epicatechin, and six (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1A2, cytosolic sulfotransferase 1A3, cytosolic sulfotransferase 1B1, cytosolic sulfotransferase 1C4, and cytosolic sulfotransferase 1E1) displayed sulfating activity toward rutin. The kinetic parameters of the cytosolic sulfotransferases that showed the strongest sulfating activities were determined. To investigate the effects of genetic polymorphisms on the sulfation of quercitrin, epicatechin, and rutin, individual panels of cytosolic sulfotransferase allozymes previously prepared were analyzed and shown to display differential sulfating activities toward each of the three flavonoids. Taken together, these results provided a biochemical basis underlying the metabolism of quercitrin, epicatechin, and rutin through sulfation in humans.

Programming Surface-Enhanced Raman Scattering of DNA Origami-templated Metamolecules.

DNA origami holds an unprecedented capability on assembling metallic nanoparticles into designer plasmonic metamolecules of emerging properties, including surface-enhanced Raman scattering (SERS). SERS metamolecules were produced by positioning nanoparticles in close proximity to each other on a DNA origami template for Raman enhancement. In earlier reports, SERS metamolecules were generally assembled into clusters containing small number of nanoparticles (2, 3, or 4) and thus had limited programmability over SERS. Herein, we expanded the structural complexity of SERS metamolecules by increasing the number of nanoparticles and by arranging them into sophisticated configurations. DNA origami hexagon tile was used as the assembling template to fabricate clusters consisting of 6, 7, 12, 18, and 30+ metallic nanoparticles. Programmable SERS was realized via controlling the size, number, or spatial arrangement of nanoparticles. We believe this method offers a general platform for fabricating sophisticated nanodevices with programmable SERS that may be applied to a variety of fields including plasmonics, nanophotonics, and sensing.

Advances in Understanding Mobilization Processes of Trace Metals in Marine Sediments.

Different mobilization mechanisms control the metal distribution in surface sediments of the Belgium coastal zone (BCZ) and the anoxic Gotland basin (GB). This mobilization was studied using DGT (diffusive gradients in thin films): vertical one-dimensional (1D) profiles of Cd, Co, Cu, Fe, Mn, Ni, Pb, and Zn were measured at 5 mm intervals, while two-dimensional (2D) high-resolution (100 µm) images of smaller zones of the sediment profile were obtained on separate DGT probes. Removal of dissolved Cd, Cu, and Pb in BCZ sediments caused steep vertical gradients at the sediment-water interface that were well replicated in 1D profiles and 2D images. While 1D profiles showed apparent coincident maxima of Co, Mn, and Fe, 2D images revealed mutually exclusive Co and Fe mobilization. Correlation analysis supported this observation and showed a consistent linkage between Co and Mn. Sharp maxima of some metals in the vertical 1D profiles of GB sediment were attributed to localized mobilization in microniches. Examination of an ∼1 mm diameter Cu and Ni maximum in 2D, defined by ∼300 data points, showed that the metals were supplied from localized decomposition of reactive organic material, rather than from reductively dissolving Fe or Mn oxides, and that they were removed as their sulfides.

Programmable DNA Nanoindicator-Based Platform for Large-Scale Square Root Logic Biocomputing.

The prospect of programming molecular computing systems to realize complex autonomous tasks has advanced the design of synthetic biochemical logic circuits. One way to implement digital and analog integrated circuits is to use noncovalent hybridization and strand displacement reactions in cell-free and enzyme-free nucleic acid systems. To date, DNA-based circuits involving tens of logic gates capable of implementing basic and complex logic functions have been demonstrated experimentally. However, most of these circuits are still incapable of realizing complex mathematical operations, such as square root logic operations, which can only be carried out with 4 bit binary numbers. A high-capacity DNA biocomputing system is demonstrated through the development of a 10 bit square root logic circuit. It can calculate the square root of a 10 bit binary number (within the decimal integer 900) by designing DNA sequences and programming DNA strand displacement reactions. The input signals are optimized through the output feedback to improve performance in more complex logical operations. This study provides a more universal approach for applications in biotechnology and bioengineering.

Split aptamer-based detection of adenosine triphosphate using surface enhanced Raman spectroscopy and two kinds of gold nanoparticles.

An ultrasensitive and highly selective method is described for the determination of adenosine triphosphate (ATP) via surface-enhanced Raman scattering (SERS). Two split aptamers are used for specific recognition of ATP. They were attached to two SERS substrates. The first was placed on a nanolayer of gold nanoparticle-decorated graphene oxide (GO/Au3), and the other on gold nanoparticles (Au2). When ATP is introduced, it will interact with the split aptamers on the gold nanostructures to form a sandwich structure that brings the GO/Au3 nanolayer and the Au2 nanoparticle in close proximity. Consequently, the SERS signal, best measured at 1072 cm-1, is strongly enhanced. The sandwich structure also displays good water solubility and stability. Under optimized conditions, the SERS signal increases in the 10 pM - 10 nM ATP concentration range, and the limit of detection (LOD) is 0.85 pM. The method was applied to the determination of ATP in spiked human serum, and the LODs in serum and buffer are comparable. In our perception, the method has a wide scope in that numerous other aptamers may be used. This may result in a variety of other highly sensitive aptasensors for use in in-vitro diagnostics. Graphical abstract Schematic presentation of a self-assembly sandwich nanostructure as unique SERS assay platform for the sensitive detection of ATP.

The lipid-lowering effects of Danhong and Huangqi injections: a meta-analysis of clinical controlled trials.

BACKGROUND: Dyslipidaemia is a major risk factor for coronary heart disease (CHD). Danhong and Huangqi injections, two traditional Chinese medicine prescriptions, have been widely studied regarding their lipid-lowering properties. However, the results were inconsistent and inconclusive. Thus, we conducted this meta-analysis of clinical controlled trials to clarify the lipid-lowering effects of Danhong and Huangqi injections. METHODS: The databases including PubMed, Google Scholar, Web of Science, Cochrane Library, Wanfang Database, CNKI and VIP were searched. The following information was obtained from each study: first author, age, gender, ethnicity, health condition, treatment dose, treatment duration, sample size, mean and standard deviation or standard error of lipid variables before and after treatment. The changes in lipid levels from pre- to post-treatment were calculated and compared between the control groups and the treatment groups in this meta-analysis. RESULTS: Forty-four studies (5021 subjects) and 7 studies (542 subjects) were respectively identified for Danhong and Huangqi injections. Compared with the control groups, Danhong injection yielded a significant reduction in triglycerides (TG) [standardized mean difference (SMD) = - 0.76, 95% confidence interval (CI) = (- 0.91, - 0.61), P <  0.001], total cholesterol (TC) [SMD = - 1.29, 95% CI = (- 1.56, - 1.03), P <  0.001] and low-density lipoprotein cholesterol (LDL-C) [SMD = - 0.76, 95% CI = (- 0.93, - 0.59), P <  0.001], and a significant elevation in high-density lipoprotein cholesterol (HDL-C) [SMD = 0.70, 95% CI = (0.41, 0.98), P <  0.001]. Regarding Huangqi injection, it yielded a significant reduction in TC [SMD = - 1.13, 95% CI = (- 2.09, - 0.16), P = 0.02] and marginally in TG [SMD = - 1.27, 95% CI = (- 2.53, 0.00), P = 0.05] comparing with the control groups. CONCLUSIONS: Danhong injection can effectively decrease the plasma levels of TG, TC and LDL-C, and increase HDL-C levels. Huangqi injection also has significant effects on TG and TC reduction, but not as powerful as Danhong injection.

Colorimetric Strategy for Highly Sensitive and Selective Simultaneous Detection of Histidine and Cysteine Based on G-Quadruplex-Cu(II) Metalloenzyme.

In this present work, we proposed a colorimetric strategy for simultaneous detection of histidine and cysteine based on G-quadruplex-Cu(II) metalloenzyme for the first time. Because of the adding of histidine or cysteine, the formation of G-quadruplex-Cu(II) metalloenzyme will be disturbed, thus the catalytic activity to TMB-H2O2 reaction is inversely proportional to the concentration of histidine or cysteine. With this strategy, the limit of detection in experimental measurement for histidine and cysteine is 10 nM and 5 nM, respectively, which are both lower than previous colorimetric arrays. With the help of NEM, cysteine is alkylated and the reaction between Cu(2+) is inhibited, so the selectivity can also be guaranteed. The cost is quite low since the developed array is label free and enzyme free by using low-cost DNA and Cu(2+). More importantly, the colorimetric detection operation is very simple without any further modification process.

Sulfation of 6-hydroxymelatonin, N-acetylserotonin and 4-hydroxyramelteon by the human cytosolic sulfotransferases (SULTs).

1. This study aimed to investigate the involvement of sulfation in the metabolism of 6-hydroxymelatonin (6-OH-Mel), N-acetylserotonin (NAS) and 4-hydroxyramelteon (4-OH-Ram), and to identify and characterize the human cytosolic sulfotransferases (SULTs) capable of sulfating these drug compounds. 2. A systematic analysis using 13 known human SULTs revealed that SULT1A1 displayed the strongest activity in catalyzing the sulfation of 6-OH-Mel and 4-OH-Ram, whereas SULT1C4 exhibited the strongest sulfating-activity towards NAS. pH-dependence and kinetic parameters of these SULT enzymes in mediating the sulfation of respective drug compounds were determined. A metabolic labeling study showed the generation and release of [35S]sulfated 6-OH-Mel, NAS and 4-OH-Ram by HepG2 human hepatoma cells and Caco-2 human colon adenocarcinoma cells labeled with [35S]sulfate in the presence of these drug compounds. Cytosols of human lung, liver, kidney and small intestine were examined to verify the presence of 6-OH-Mel-, NAS- and 4-OH-Ram-sulfating activity in vivo. Of the four human organ samples tested, small intestine and liver cytosols displayed considerably higher 6-OH-Mel-, NAS- and 4-OH-Ram-sulfating activities than those of lung and kidney. 3. Collectively, these results provided a molecular basis for the metabolism of 6-OH-Mel, NAS and 4-OH-Ram through sulfation.

Sulfation of 6-Gingerol by the Human Cytosolic Sulfotransferases: A Systematic Analysis.

Previous studies have demonstrated the presence of the sulfated form of 6-gingerol, a major pharmacologically active component of ginger, in plasma samples of normal human subjects who were administered 6-gingerol. The current study was designed to systematically identify the major human cytosolic sulfotransferase enzyme(s) capable of mediating the sulfation of 6-gingerol. Of the 13 known human cytosolic sulfotransferases examined, six (SULT1A1, SULT1A2, SULT1A3, SULT1B1, SULT1C4, SULT1E1) displayed significant sulfating activity toward 6-gingerol. Kinetic parameters of SULT1A1, SULT1A3, SULT1C4, and SULT1E1 that showed stronger 6-gingerol-sulfating activity were determined. Of the four human organ samples tested, small intestine and liver cytosols displayed considerably higher 6-gingerol-sulfating activity than those of the lung and kidney. Moreover, sulfation of 6-gingerol was shown to occur in HepG2 human hepatoma cells and Caco-2 human colon adenocarcinoma cells under the metabolic setting. Collectively, these results provided useful information relevant to the metabolism of 6-gingerol through sulfation both in vitro and in vivo.

Sulfation of afimoxifene, endoxifen, raloxifene, and fulvestrant by the human cytosolic sulfotransferases (SULTs): A systematic analysis.

Previous studies demonstrated that sulfate conjugation is involved in the metabolism of three commonly used breast cancer drugs, tamoxifen, raloxifene and fulvestrant. The current study was designed to systematically identify the human cytosolic sulfotransferases (SULTs) that are capable of sulfating raloxifene, fulvestrant, and two active metabolites of tamoxifen, afimoxifene and endoxifen. A systematic analysis using 13 known human SULTs revealed SULT1A1 and SULT1C4 as the major SULTs responsible for the sulfation of afimoxifene, endoxifen, raloxifene and fulvestrant. Kinetic parameters of these two human SULTs in catalyzing the sulfation of these drug compounds were determined. Sulfation of afimoxifene, endoxifen, raloxifene and fulvestrant under metabolic conditions was examined using HepG2 human hepatoma cells and MCF-7 breast cancer cells. Moreover, human intestine, kidney, liver, and lung cytosols were examined to verify the presence of afimoxifene/endoxifen/raloxifene/fulvestrant-sulfating activity.

Observation on the changes of visual field and optic nerve fiber layer thickness in patients with early diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM) and is a leading cause of vision loss. Early detection of DR-related neurodegenerative changes is crucial for effective management and prevention of vision loss in diabetic patients. METHODS: In this study, we employed spectral-domain polarization-sensitive optical coherence tomography (SD PS-OCT) to assess retinal nerve fiber layer (RNFL) changes in 120 eyes from 60 types 1 DM patients without clinical DR and 60 age-matched healthy controls. Visual field testing was performed to evaluate mean sensitivity (MS) and mean defect (MD) as indicators of visual function. RESULTS: SD PS-OCT measurements revealed significant reductions in RNFL birefringence, retardation, and thickness in type 1 DM patients compared to healthy controls. Visual field testing showed decreased MS and increased MD in DM patients, indicating functional impairment correlated with RNFL alterations. CONCLUSION: Our findings demonstrate early neurodegenerative changes in the RNFL of type 1 DM patients without clinical DR, highlighting the potential of SD PS-OCT as a sensitive tool for early detection of subclinical DR-related neurodegeneration. These results underscore the importance of regular ophthalmic screenings in diabetic patients to enable timely intervention and prevent vision-threatening complications.