As the number of patients with metabolic hypertension (MH) is increasing, there is an essential require for global measures to prevent and treat MH. Flavonoids such as buddleoside (BUD) from
...Chrysanthemum indicum
L. are the main pharmacological components of cardiovascular activities. Previous studies have suggested that the buddleoside-rich
Chrysanthemum indicum
L. extract (BUDE) can reduce blood pressure in spontaneously hypertensive rats (SHR). However, its effect on MH and how it works remains to be researched. In this study, it was observed that BUDE could lower blood pressure, improve dyslipidemia, and decrease the level of plasma LPS in MH rats. Moreover, BUDE improved intestinal flora and increased the expression of occludin and claudin-1 in the colon, and improved the pathological injury of the colon. Western bolt and qRT-PCR experiments showed that BUDE could down-regulate TLR4 and MyD88 protein and mRNA expression and inhibit phosphorylation of IKKβ, IκBα and NF-κB p65 in vessels of MH rats. These results showed that BUDE could regulate intestinal flora, improve intestinal barrier function, reduce the production and penetration of LPS, thereby inhibiting the vascular TLR4/MyD88 pathway, improving vascular endothelial function, and ultimately lowering blood pressure in MH rats. This study provides a new mechanism of BUDE against MH by inhibiting the enteric-origin LPS/TLR4 pathway.
Animal‐derived anti‐IgG secondary antibodies are currently employed to stain and screen of human monoclonal antibody(mAb)‐producing cells, but using animal‐derived antibodies may raise the concerns ...of high cost, complicated operations and biological safety issues in biopharmaceutical manufacturing. Nanobodies(VHHs) are attractive forms of antibodies for their straightforward engineering and expression in both eukaryotic and prokaryotic systems. Using phage‐displayed immune llama VHH library, we identified new anti‐Fc VHHs that could bind to human Fc with high affinity. In GFP fusion format, the anti‐Fc VHH‐GFP generated dramatically stronger FACS signals than AF488 conjugated anti‐IgG antibodies when used for staining mAb‐producing CHO cells. Furthermore, preparative sorting of CHO cells based on anti‐Fc VHH‐GFP staining resulted in the enrichment of cell lines capable of synthesizing mAb at high productivity. This safe and cost‐efficient anti‐Fc VHH‐GFP may optimize the process of generating highly productive cell lines for therapeutic mAb production compared to conventional animal‐derived fluorescent antibodies.
Controlled synthesis of efficient core-shell non-precious metal catalysts for oxygen reduction reaction (ORR) is undoubtedly crucial but challenging for the extensive application of fuel cells and ...metal-air batteries. Herein, we prepared a core-shell structured Fe/FeCx nanoparticles and porous carbon composited catalyst (Fe/FeCx@NC) via a facile two-step heat treatment strategy. The Fe/FeCx@NC-800−0.5 prepared with secondary anneal at 800 °C for 0.5 h exhibits superior ORR performance to the commercial Pt/C in terms of comparable onset potential, higher half-wave potential, and outstanding long-term durability in alkaline media. Through combining the physical and electrochemical characterizations of Fe/FeCx@NC-T−t with different anneal temperature and precursors, the outstanding ORR performance of Fe/FeCx@NC-800−0.5 is caused by the synergistic effect between Fe/FeCx core and enriched pyridinic N- and graphitic N-doped carbon shell as well as porous carbon with large specific surface area. The structure-activity relationship of core-shell structured Fe–N–C catalysts for ORR provides directions for the development of advanced nonprecious metals catalysts.
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•A porous Fe/FeCx core-NC shell catalyst was prepared by two-step anneal method.•The Fe/FeCx@NC-800−0.5 shows superior ORR activity and stability than Pt/C.•Synergistic effect of Fe/FeCx core and carbon shell plays essential role for ORR.
CALR mutations are detected in about 50% of persons of predominately European descent with essential thrombocythemia (ET) or primary myelofibrosis (PMF) with wild-type alleles of JAK2 and MPL. We ...studied 1088 Chinese with diverse myeloproliferative neoplasms including ET (N=234) and PMF (N=50) without JAK2(V617F) or MPL exon 10 mutations. CALR mutation was detected in 53% (95% CI, 46-60%) of subjects with ET and 56% (95% CI, 41-70%) of subjects with PMF. 152 CALR mutations were identified clustering into 15 types including deletions (N=8), insertions (N=3) and complex indels (N=4). We also identified 9 new mutations. Mean (±SD) mutant allele burden was 31±12% (range, 0.5-69%). Persons with PMF had higher CALR mutant allele burdens than those with ET (38±8% vs. 29±12%; P<0.001). Amongst persons with CALR mutations, those with PMF had different clinical features from those with ET. These data may be useful for diagnosing ET and PMF in Chinese who are about 40% of all persons with ET and PMF and for monitoring therapy-response. They also highlight similarities and differences in CALR mutations between Chinese and persons of predominately European descent with these diseases.
Background
Calreticulin (CALR) mutations were recently identified in a substantial proportion of persons with essential thrombocythemia (ET) and with primary myelofibrosis (PMF) without JAK2
V617F
. ...Consequently rapid, sensitive, and specific methods to detect and quantify these mutations are needed.
Methods
We studied samples from 1088 persons with myeloproliferative neoplasms (MPNs) including 421 JAK2
V617F
negative subjects with ET, PMF, polycythemia vera (PV), chronic myeloid leukemia (CML) and hyper-eosinophilic syndrome (HES). Detection of CALR exon 9 mutations was done by PCR amplification followed by fragment length analysis and direct sequencing. Dilution assays were used to determine CALR mutant allele burden.
Results
We detected CALR mutations in blood and bone marrow samples from 152 subjects with ET and with PMF but not in samples from normal or persons with PV, CML, or HES. CALR mutant peaks were distinct from wild-type peaks and dilution experiments indicated a sensitivity level of 0.5-5% for a CALR mutant allele in a wild-type background. Diverse types of mutations were detected including deletions, insertions, and complex indels. All mutations were confirmed by direct sequencing. We also used dilution experiments to quantify mutant allele burden. We were able to reproducibly detect mutant allele levels as low 5% (0.5-5%) in a wild-type background.
Conclusions
PCR amplification followed by fragment length analysis is a rapid, sensitive, and specific method for screening persons with MPNs for CALR mutations, especially those with ET and PMF and for estimating mutant allele burden.
BACKGROUND Surgical care of the hand plays a crucial role in the medical field, as problems with the hand can profoundly affect a patient's quality of life and function. In order to meet the needs of ...patients, improve patient satisfaction and improve treatment outcomes, high-quality service models have been introduced in the field of nursing. AIM To explore the effect analysis of applying high-quality service model to surgical nursing. METHODS We conducted a retrospective study of patients who underwent hand surgery at our hospital between 2019 and 2022, using a quality service model that included improved patient education, pain management, care team collaboration, and effective communication. Another group of patients received traditional care as a control group. We compared postoperative recovery, satisfaction, complication rate, and length of hospital stay between the two groups. Inferential statistics were used to compare the difference between the two groups by independent sample t test, Chi-square test and other methods to evaluate the effect of intervention measures. RESULTS Postoperative recovery time decreased from 17.8 ± 2.3 d to 14.5 ± 2.1 d, pain score decreased from 4.7 ± 1.9 to 3.2 ± 1.4, and hand function score increased from 78.4 ± 7.1 to 88.5 ± 6.2. In terms of patient satisfaction, the quality service model group scored 87.3 ± 5.6 points, which was significantly higher than that of the traditional care group (74.6 ± 6.3 points). At the same time, patients' understanding of medical information also improved from 6.9 ± 1.4 to 8.6 ± 1.2. In terms of postoperative complications, the application of the quality service model reduced the incidence of postoperative complications from 26% to 10%, the incidence of infection from 12% to 5%, and the incidence of bleeding from 10% to 3%. The reduction in these data indicates that the quality service model plays a positive role in reducing the risk of complications. In addition, the average hospital stay of patients in the quality service model group was shortened from 6.8 ± 1.5 d to 5.2 ± 1.3 d, and the hospitalization cost was also reduced from 2800 ± 600 yuan to 2500 ± 500 yuan. CONCLUSION Applying a quality service model to hand surgery care can significantly improve patient clinical outcomes, including faster recovery, less pain, greater satisfaction, and reduced complication rates.
The 5-formyluracil (5-foU), a major mutagenic oxidative damage of thymine, is removed from DNA by Nth, Nei and MutM in Escherichia coli. However, DNA polymerases can also replicate past the 5-foU by ...incorporating C and G opposite the lesion, although the mechanism of correction of the incorporated bases is still unknown. In this study, using a borohydride-trapping assay, we identified a protein trapped by a 5-foU/C-containing oligonucleotide in an extract from E. coli mutM nth nei mutant. The protein was subsequently purified from the E. coli mutM nth nei mutant and was identified as KsgA, a 16S rRNA adenine methyltransferase. Recombinant KsgA also formed the trapped complex with 5-foU/C- and thymine glycol (Tg)/C-containing oligonucleotides. Furthermore, KsgA excised C opposite 5-foU, Tg and 5-hydroxymethyluracil (5-hmU) from duplex oligonucleotides via a β-elimination reaction, whereas it could not remove the damaged base. In contrast, KsgA did not remove C opposite normal bases, 7,8-dihydro-8-oxoguanine and 2-hydroxyadenine. Finally, the introduction of the ksgA mutation increased spontaneous mutations in E. coli mutM mutY and nth nei mutants. These results demonstrate that KsgA has a novel DNA glycosylase/AP lyase activity for C mispaired with oxidized T that prevents the formation of mutations, which is in addition to its known rRNA adenine methyltransferase activity essential for ribosome biogenesis.
This study aims to investigate the preventive effect of Dendrobium officinale in LPS-induced intestinal mucosal damage. Forty SPF-grade C57 BL/6 J male mice were randomly divided into normal ...group(NC), model group(LPS), and two superfine powder groups of Dendrobium officinale(DOF)(DOF-L, 0.30 g·kg~(-1)and DOF-H, 0.60 g·kg~(-1), respectively), with 10 mice in each group. DOF superfine powder suspension was given via oral administration to mice for 7 days, while the mice in NC and LPS groups received the same volume of saline for 7 days. On the eighth day, the mice in LPS group and DOF treatment groups were injected with LPS(5 mg·kg~(-1)) by intraperitoneal injection to establish the intestinal mucosal injury model, while the mice in NC group were injected with the same volume of sterile saline in the same manner. Six hours after injection with LPS or saline, plasma and the intestinal tissue were collected. The diamine oxidase(DAO) and D-lactate levels in plasma were detected with a biochemical method. The levels of proinflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in plasma were detected by ELISA. The histomorphology and ultrastructure of mouse ileum tissues were observed by hematoxylin-eosin(HE) staining in optical microscope and transmission electron microscope(TEM). The expression and distribution of tight junction(TJ) proteins claudin-1, occludin and F4/80 were detected by immunohistochemistry while the protein expression levels of Toll-like receptor 4(TLR-4) and nuclear factor kappa B p65(NF-κB p65) in jejunum were detected by Western blot. The experimental results showed that continuous intragastric administration of D. officinale superfine powder for 7 days obviously alleviated the damage and ultrastructural changes of intestinal mucosa induced by LPS; significantly decreased DAO and D-lactate levels in plasma in model group(P<0.05); up-regulated the protein expression of claudin-1 and occludin in ileum tissues; down-regulated the protein expression of TLR-4 and NF-κB p65 in jejunum tissues(P<0.01); significantly decreased TNF-α and IL-6 levels in plasma(P<0.05); and decreased the infiltration of F4/80~+ macrophage cells. Our results suggested that D. officinale had significant protective effects on LPS-induced intestinal mucosal damage and reduced intestinal permeability. The mechanism might be related to its effects of inhibiting inflammation via TLR-4/NF-κB p65, and up-regulating the expression of tight junction proteins.
Abstract CALR mutations are detected in about 50% of persons of predominately European descent with essential thrombocythemia (ET) or primary myelofibrosis (PMF) with wild-type alleles of JAK2 and ...MPL. We studied 1088 Chinese with diverse myeloproliferative neoplasms including ET ( N = 234) and PMF ( N = 50) without JAK2V617F or MPL exon 10 mutations. CALR mutation was detected in 53% (95% CI, 46–60%) of subjects with ET and 56% (95% CI, 41–70%) of subjects with PMF. 152 CALR mutations were identified clustering into 15 types including deletions ( N = 8), insertions ( N = 3) and complex indels ( N = 4). We also identified 9 new mutations. Mean (±SD) mutant allele burden was 31 ± 12% (range, 0.5–69%). Persons with PMF had higher CALR mutant allele burdens than those with ET (38 ± 8% vs. 29 ± 12%; P < 0.001). Amongst persons with CALR mutations, those with PMF had different clinical features from those with ET. These data may be useful for diagnosing ET and PMF in Chinese who are about 40% of all persons with ET and PMF and for monitoring therapy-response. They also highlight similarities and differences in CALR mutations between Chinese and persons of predominately European descent with these diseases.
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