Prednisone Acetate Research Articles

Alterations of gut microbiota and metabolome are associated with primary nephrotic syndrome in children

BackgroundPrimary nephrotic syndrome (PNS) is a common glomerular disease in children. Dysbiosis of gut microbiota acts as a cause of Treg abnormalities. However, the intestinal metabolic impact of PNS with children remains poorly understood. This study aims to investigate the dynamic changes of gut microbiota and it’s metabolism in children with PNS.MethodsFecal and peripheral blood samples were separately collected from patients with initial diagnosis of PNS (PNS_In group), recurrence of PNS (PNS_Re group), and healthy controls (HCs group). The fecal samples were subjected to the microbiome and metabolome by the multi-omics analysis. Additionally, the peripheral blood samples were collected and associated inflammatory indicators were determined.ResultsWe found that in PNS_In group, lipopolysaccharide (LPS), pro-inflammatory interleukin (IL)-6, IL-17A, IL-23p19, and IL-1β were significantly increased compared with those in HCs group. However, these abnormalities were dramatically reversed in PNS_Re group treated with prednisone acetate. Moreover, the crucial Treg/Th17 axis in PNS inflammation was also proved to be discriminated between PNS and HCs. Gut microbial dysbiosis was identified in PNS_In and PNS_Re patients. At the genus level, compared to HCs group, the abundance of Faecalibacterium notably changed in PNS_In and PNS_Re groups, showing negatively correlated with inflammatory factors. Moreover, the fecal metabolome of PNS_In and PNS_Re remarkably altered with the major impacts in the metabolism of phenylalanine, ABC transporters, arginine and proline.ConclusionThe dynamic changes of gut microbiota and associated metabolites are closely correlated with initial period and recurrence of PNS in children via probably regulating inflammatory Th17/Treg axis, which may potentially provide novel targets for the control of the disease.Clinical trial numberNot applicable.

Increased thermal stability and catalytic efficiency of 3-ketosteroid Δ1-dehydrogenase5 from Arthrobacter simplex significantly reduces enzyme dosage in prednisone acetate biosynthesis

The 3-ketosteroid-Δ1-dehydrogenase5 (KsdD5) from Arthrobacter simplex converts cortisone acetate to prednisone acetate, an important step in steroid catabolism. To achieve sustainable and efficient enzyme production, we employed computer-aided screening, structural analysis, and combinatorial experiments to identify engineered KsdD5 variants (M1 and M3) with dual advantages of stability and active sites. M1 had a 8.2-fold longer half-life (19.6 h at 30 °C) than KsdD5-WT, an 11.8 °C higher half-inactivation temperature (T5015min), and a 10.6 °C higher melting temperature (Tm). M3 had 3.82-fold higher catalytic activity than WT, a 3.9-fold longer half-life at 30 °C, and higher T5015min and Tm by 14 °C and 6.9 °C, respectively. Furthermore, kinetic and microscale thermophoresis analyses revealed M3 exhibited higher catalytic efficiency due to its larger enzymatic channel. Molecular dynamics simulations showed M1 promoted tighter secondary structure packing, reduced residue flexibility, and increased hydrogen bond formation, ensuring enzyme stability and activity at elevated temperatures. Under industrial conditions, M1 converted >96 % cortisone acetate within 12 h at 30 °C with a 60 g·L−1 substrate dosage and 6 g·L−1 cell mass, whereas the M3 conversion rate was 95 %. This study demonstrates a robust strategy for developing efficient enzyme mutants, facilitating sustainable industrial production of prednisone acetate with a minimal enzyme dosage.

Rapid screening of prednisolone acetate adulterants in health foods using colloidal gold immunochromatographic assay

In this study, a rapid detection method utilizing colloidal gold immunochromatography (CG-ICA) was developed for the detection of illegally added prednisone acetate in health foods. Initially, the preparation conditions of colloidal gold solution were optimized. The optimal potassium carbonate dosage, antibody diluent type, antibody dosage, probe labeling time, blocking time and BSA dosage were determined. Technical analysis was performed to ensure that the established CG-ICA exhibited satisfactory color development and inhibition rates. Under optimized conditions, the cut-off value of CG-ICA was 250 μg/kg. The assay demonstrated a sensitivity of 100 %, a false positive rate of 8 %, and a false negative rate of 0, indicating high specificity for prednisone acetate. The results obtained from testing actual samples were consistent with those obtained using LC-MS/MS, thereby verifying the reliability of the developed method. This method offers robust support for the rapid detection of illegally added prednisone acetate in health foods.

Anti-inflammatory, antioxidant and anti-mitophagy effects of trans sodium crocetinate on experimental autoimmune encephalomyelitis in BALB/C57 mice.

Multiple sclerosis (MS) is an autoimmune disorder characterized by the degeneration of myelin and inflammation in the central nervous system. Trans sodium crocetinate (TSC), a novel synthetic carotenoid compound, possesses antioxidant, anti-inflammatory and neuroprotective effects. This study aimed to evaluate the protective effects of TSC against the development of experimental autoimmune encephalomyelitis (EAE), a well-established model for MS. Female BALB/C57 mice were divided into different groups, including control, EAE, vehicle, TSC-treated (25, 50, and 100mg/kg, administered via gavage) + EAE, methyl prednisone acetate + EAE, and TSC-treated (100mg/kg, administered via gavage for 28 days) groups. EAE was induced using MOG35-55, complete Freund's adjuvant, and pertussis toxin. In the mice spinal cord tissues, the oxidative markers (GSH and MDA) were measured using spectrophotometry and histological evaluation was performed. Mitophagic pathway proteins (PINK1and PARKIN) and inflammatory factors (IL-1β and TNF-α) were evaluated by western blot. Following 21 days post-induction, EAE mice exhibited weight loss, and the paralysis scores increased on day 13 but recovered after TSC (100mg/kg) administration on day 16. Furthermore, TSC (50 and 100mg/kg) reversed the altered levels of MDA and GSH in the spinal cord tissue of EAE mice. TSC (100mg/kg) also decreased microgliosis, demyelination, and the levels of inflammatory markers IL-1β and TNF-α. Notably, TSC (100mg/kg) modulated the mitophagy pathway by reducing PINK1 and Parkin protein levels.These findings demonstrate that TSC protects spinal cord tissue against EAE-induced MS through anti-inflammatory, antioxidant, and anti-mitophagy mechanisms.

Effects of acupuncture for Bell's palsy patients in the acute phase and its impact on facial nerve edema: a study protocol for a randomized, controlled trial.

Bell's palsy is an acute peripheral facial neuropathy, which is one of the most common causes of facial palsy of lower motor neurons. Facial nerve swelling is commonly observed in Bell's palsy. Acupuncture therapy has been widely used in the treatment of Bell's palsy. However, whether acupuncture can be effectively used in the acute stage is still controversial. There are no clinical trials conducted previously to evaluate the effect of acupuncture on facial nerve edema in Bell's palsy patients. The study aims to evaluate the potential efficacy of different acupuncture modalities on Bell's palsy patients in the acute phase, its effect on facial nerve edema, and to preliminarily explore its possible mechanism. In this randomized, controlled trial, 165 Bell's palsy patients with unilateral onset within 3 days will be recruited and randomly assigned to either the electroacupuncture group (n = 33), the acupuncture group (n = 33), the sham acupuncture group (n = 33), the blank control group (n = 33), or the acupuncture control group (n = 33) in a 1:1:1:1:1 ratio. The participants will receive 4 weeks of treatment and 8 weeks of follow-up. The five groups of participants will receive the following treatments: A: Electroacupuncture + Medication (prednisone acetate tablets, mecobalamin tablets, and vitamin B1 tablets); B: Acupuncture + Medication; C: Sham Acupuncture + Medication; D: Medication only; and E: Acupuncture only. The primary outcome will be the effectiveness rate of different acupuncture modalities in improving facial nerve function after the intervention period. The secondary outcomes will be the recovery speed, the diameter of the facial nerve, the echo intensity and thickness of facial muscles, blood flow parameters of the facial artery, the serum inflammatory level, safety evaluation, and adverse events. Preliminary exploration of its mechanism of action occurs through inflammation and immune response. The difference between groups will be assessed using repeated measure analysis of covariance (ANCOVA) and trend chi-square. The trial will evaluate the efficacy and facial nerve edema of acupuncture for Bell's palsy patients in the acute phase and preliminarily explore its possible mechanism. The results thus may provide evidence for clinical application. https://www.chictr.org.cn/bin/project/edit?pid=133211, identifier ChiCTR2100050815.

Effects of intracameral dexamethasone injection versus topical steroids post phacoemulsification operation

Introduction Cataract surgery is one of the most commonly performed surgeries worldwide, with nearly 20 million cases annually. Ophthalmologists usually use a prophylactic perioperative regimen consisting of topical corticosteroids and nonsteroidal anti-inflammatory drugs to reduce the risk of inflammation. However, patient compliance and other problems concerning administration with elderly patients self-administering medication drops can vary widely and a wide proportion of them fail to comply with a long-term regimen. Aim Evaluation of intracameral dexamethasone injection efficacy and safety versus topical anti-inflammatory eyedrop regimens for postphacoemulsification inflammation for better postoperative management of cataract patients. Methodology A prospective randomized clinical trial. Participants were divided into two groups in group A, dexamethasone sodium-phosphate (0.4 mg/0.1 mL) was injected intracamerally at the end of phacoemulsification surgeries without topical steroids postoperatively. Group B: took the routine postoperative anti-inflammatory steroidal and nonsteroidal eye drop regimen. Results Included the corneal thickness that showed no discernible change between postoperative numbers in both groups. Nevertheless, there was a statistically significant increase in CCT postoperatively in both groups. The intraocular pressure decreased significantly after 1 month of phacoemulsification operation in both groups simultaneously. Postoperative cell density and hexagonality were significantly lower in both groups compared with preoperative values. There was also no significant difference between both groups regarding the anterior chamber cells’ index. Moreover, the Dexamethasone-injected group showed better compliance on the postoperative visits regarding their prescriptions taken after the operation compared with the Prednisone acetate eye drops group. Conclusions Better results regarding the severity of the endothelial damage with the use of a single intraoperative injection post phacoemulsification compared with the group who did not get injected but took postoperative prednisone acetate eye drops. The obligatory single intraoperative injection of dexamethasone has handled the poor compliance of some patients’ post phacoemulsification.

Efficacy of abiraterone combined with prednisone in castration-resistant prostate cancer and its impact on miR-221/222 expression.

To assess the therapeutic efficacy of abiraterone combined with prednisone in patients with castration-resistant prostate cancer (CRPC) and investigate its effects on miR-221/222 expression. A retrospective cohort of 43 CRPC patients from Henan Provincial People's Hospital, People's Hospital of Zhengzhou University was divided into two groups: the treated group (n=22, treated with abiraterone and prednisone) and the control group (n=21, treated with prednisone acetate alone). Expression of miR-221/222 was quantified in CRPC cell lines using quantitative fluorescence polymerase chain reaction. The treated group demonstrated significantly higher rates of bone pain relief and prostate-specific antigen (PSA) response compared to the control group (P=0.032, P=0.022, respectively). Post-treatment, the treated group also showed increased Karnofsky Performance Status scores and reduced plasma testosterone levels relative to controls (P=0.021, P=0.016). There was no significant difference in the incidence of adverse reactions between the treated group (31.82%) and the control group (28.57%) (P=0.125). Abiraterone combined with prednisone effectively relieves bone pain and improves PSA response rates in CRPC patients, suggesting benefits in enhancing quality of life and reducing testosterone levels without increasing adverse reactions. This therapy appears to have a safety profile comparable to that of conventional treatments.

Dynamic changes of Th1/Th2/Th17 cytokines and hBD-2/3 in erosive oral lichen planus patients saliva before and after prednisone acetate treatment

ObjectiveThis study aimed to investigate the expression of T helper 1 (Th1)/Th2/Th17- related cytokines and human beta defensins 2 and 3 (hBD-2 and -3) in the saliva of patients with erosive oral lichen planus (EOLP) and to explore their role in the pathogenesis of EOLP and the effects of glucocorticoids on EOLP. MethodsA total of 30 patients with EOLP and 20 age- and sex-matched healthy individuals were included in this study. The patients were treated with prednisone at a dose of 0.4 mg/(kg·d) for 1 week and examined before and after treatment. Unstimulated whole saliva samples were collected to determine the levels of cytokines (interleukin 1 beta [IL-1β], tumour necrosis factor alpha [TNF]-α, interferon gamma [IFN-γ], IL-4, IL-6, IL-10 and IL-17) by cytometric bead array and those of hBD-2 and -3 b y enzyme-linked immunosorbent assay. In addition, oral rinse samples were collected to detect Candida load. ResultsThe levels of salivary IL-1β, IL-6, hBD-2 and hBD-3 were higher and the IFN-γ/IL-4 and IL-1β/IL-6 ratios were lower in patients with EOLP than in healthy individuals. In patients with EOLP, hBD-2 levels were positively correlated with IFN-γ levels and negatively correlated with IL-17 levels, whereas hBD-3 levels were negatively correlated with IL-17 and IL-10 levels. In addition, the prevalence of EOLP was positively correlated with IL-6 levels and negatively correlated with the IFN-γ/IL-4 ratio. The levels of IL-1β, TNF-α, IFN-γ, IL-6, hBD-2 and hBD-3 and the IFN-γ/IL-4 ratio decreased after treatment with prednisone for 1 week. The levels of IL-6, hBD-2 and hBD-3 were significantly higher in EOLP patients than in healthy individuals; while TNF-α levels and the IFN-γ/IL-4 ratio were significantly lower in EOLP patients than in healthy individuals. Furthermore, the oral counts of Candida spp. (colony forming unit [CFU]) were negatively correlated with TNF-α levels. Numerical Rating Scale(NRS) and Sign scores decreased in EOLP patients after treatment. Approximately 80 % of patients were effectively treated. Salivary TNF-α levels were significantly higher in the treatment-ineffective group than in the treatment-effective group before treatment with prednisone, and differences in salivary IL-6 levels before and after treatment were significantly higher in the treatment-effective group than in the treatment-ineffective group. ConclusionsHigh expression of IL-1β, IL-6, hBD-2 and Th1/Th2 imbalance in saliva may be associated with the pathogenesis of EOLP. IFN-γ/IL-4 balance may serve as a protective factor for EOLP. Glucocorticoids significantly alleviate the symptoms of EOLP and inhibit the expression of Th1/Th2 cytokines.

Quadruple overlapping autoimmune diseases manifested as sarcoidosis with mediastinal lymphadenopathy: a case report.

We present a rare case of a 55-year-old female patient with quadruple overlapping autoimmune diseases, including vitiligo, autoimmune hypothyroidism, ulcerative colitis, and sarcoidosis with mediastinal lymphadenopathy. The patient had been suffering from vitiligo since 2003 and was diagnosed with autoimmune hypothyroidism and ulcerative colitis through thyroid ultrasound and colonoscopy, respectively. After physical examination, mediastinal lymph nodes enlargement was detected, and sarcoidosis was diagnosed through ultrasound bronchoscope-guided transbronchial needle aspiration (EBUS-TBNA), which is a quadruple overlapping sign of autoimmune disease of sarcoidosis that has not been reported previously. The patient was treated with oral Chinese medicine for leukoplakia, oral levothyroxine sodium tablets to control thyroid function, and Chinese medicine enema for colitis, with intermittent treatment for 2 years. Prednisone acetate was administered for 1 month to reduce the size of the enlarged lymph nodes. Our case highlights the importance of considering sarcoidosis as a potential diagnosis in patients with autoimmune diseases who present with mediastinal lymphadenopathy.

Hyperuricemia-Induced Acute Kidney Injury in the Context of Chronic Kidney Disease: A Case Report

ABSTRACT Hyperuricemia is an independent risk factor for acute kidney injury and chronic kidney disease. Hyperuricemia-induced acute kidney injury most commonly occurs in patients who experience tumor lysis syndrome. Herein, we report an unusual case of hyperu-ricemia-induced acute kidney injury via a crystal-dependent mechanism in a patient with chronic kidney disease. A 30-year-old Asian male patient was transferred to our hospital presenting with acute kidney injury and elevated blood uric acid level. The patient had a 5-year history of gout and 2-year history of chronic kidney disease. The pathological results of renal biopsy supported the diagnosis of focal proliferative immunoglobulin A nephropathy and subacute tubulointerstitial nephritis due to urate crystal deposition. After supportive treatment with prednisone acetate and febuxostat, the patient's proteinuria, serum creatinine, and uric acid levels decreased rapidly in the subsequent 2 months. Urate crystallization-induced acute kidney injury in patients with preexisting chronic kidney disease is unusually detectable in the clinic unless there are timely renal biopsy findings. In this case, the patient's condition improved and his renal function and serum uric acid levels recovered rapidly with prednisone acetate and febuxostat treatment. Early identification and close monitoring of uric acid levels and renal function are highly recommended for patients with chronic kidney disease. Renal biopsies should also be performed in a timely manner to identify the cause and initiate targeted therapy. We also briefly review the pathophysiology of acute kidney injury caused by hyperuricemia.

PREPARATION OF DRUG-LOADED CHITOSAN/HYDROXYAPATITE COMPOSITE MATERIAL AND ITS NUMERICAL SIMULATION IN NASAL DEFECT REPAIR

With the continuous innovation and development of materials science and tissue engineering technology, biomaterials are gradually being used to replace autologous bone and allogeneic bone grafts in clinical practice for the treatment and repair of bone defects. In this paper, L-arginine-modified chitosan/hydroxyapatite composites were prepared by solution blending of L-arginine-modified chitosan and hydroxyapatite. A hormone drug prednisone acetate was loaded into the composites by supercritical impregnation technique. The results of in vitro release showed that under the loading condition of 12 MPa and 318 K, the cumulative release amount of the drug was 74.6% in 72 h, which had an excellent sustained release effect. In addition, a numerical model of the nasal bone was developed and numerical calculations were performed to analyze and compare the stresses of the healthy nasal bone and the nasal bone repaired with CA/HA composite when subjected to a force of 100 N, in different directions. The total deformation difference at the material was 0.002-0.004 mm/mm, and the stress difference was 0.004–1.373 MPa for the nasal bone in both states, with the sagittal plane under 0–90 degrees of force. The above results indicate that the CA/HA composite has good biological and mechanical properties and can be used to repair nasal bone defects. This material and numerical calculation method can also be applied to other related bone tissue engineering and biomedical materials, which have broad application prospects.

Methylprednisolone sodium succinate retroauricular injection combined with acupuncture in the treatment of Bell's Palsy

BackgroundRetroauricular injection is a local steroid hormone administration method commonly used to treat deafness or tinnitus. The acute stage of Bell's Palsy is an acute disease that requires steroid therapy. Retroauricular injection may replace oral administration of steroid hormones in the treatment of this disease as well as reduce the occurrence of adverse reactions. MethodsThis study included patients with Bell's Palsy within seven days of onset. A total of 120 patients were enrolled as the study subjects and randomly divided into two groups: the experimental group and the control group. Both groups received routine acupuncture treatment and took a traditional Chinese medicine decoction corresponding with the syndrome type. Methylprednisolone sodium succinate was injected into the bone surface of retroauricula in the experimental group, and prednisone acetate was orally administered in the control group. The main outcome indicators were the House–Brackmann (HB) grade, the facial disability index (FDI), and time of postauricular pain after one month of treatment. ResultsThere were no significant differences in the HB grade (2.00 ± 1.06 vs. 1.88 ± 1.06, P=), FDIP (97.25 ± 6.00 vs. 97.17 ± 7.39, P=), and FDIS (0.60 ± 3.02 vs. 1.33 ± 4.27, P=) at 30 days after treatment between the two groups (P > 0.05). Postauricular pain disappeared earlier in the experimental group (3.66 ± 1.67 days) than in the control group (6.31 ± 2.34); the difference was statistically significant (P ≤ 0.001). The adverse reaction rate was lower in the experimental group (15.00%) than in the control group (21.66%). InterpretationAlthough the dose of steroid hormone injected into the bone surface of retroauricula in the treatment of Bell's Palsy is lower than the administered dose of oral hormones, it has the same curative effect; however, it has a better effect regarding to the duration of postauricular pain and adverse reactions.

Therapeutic effect of the total saponin from Panax Japonicus on experimental autoimmune encephalomyelitis by attenuating inflammation and regulating gut microbiota in mice

Ethnopharmacological relevanceRhizomes of Panax japonicus (RPJ), a traditional herbal medicine, was used for treating arthritis and physical weakness in China from the Ming dynasty. Triterpene saponins are the main bioactive components of RPJ. In this work, for the first time, we evaluate the therapeutic effect of the total saponin from RPJ (TSPJ) on experimental autoimmune encephalomyelitis (EAE) mice induced by myelin oligodendrocyte glycoprotein (MOG) 35-55, a commonly used animal model of Multiple sclerosis (MS). Aim of the studyTo evaluate the therapeutic effect of TSPJ on EAE and explored its possible underlying mechanisms. Materials and methodsEAE was induced by MOG 35-55. Mice were administrated with TSPJ (36.5 mg/kg, 73 mg/kg) and prednisone acetate (positive control) orally once daily up to 28 days postimmunization, and their neurological deficit was scored. Hematoxylin and Eosin (HE), Luxol Fast Blue (LFB), and transmission electron microscopy (TEM) were carried out to evaluate the EAE-induced pathological changes in the brain and spinal cord. IL-17a and Foxp3 levels in central nervous system (CNS)were evaluated by immunohistochemical staining. The changes in IL-1β, IL-6, and TNF-α levels in serum and CNS were measured with ELISA. Quantitative reverse transcription PCR (qRT-PCR) was used to access mRNA expression in CNS of the above indices. The percentages of Th1, Th2, Th17and Treg cells in spleen were determined by Flow Cytometry (FCM). Furthermore, 16S rDNA sequencing was used to detect the intestinal flora of mice in each group. In vitro studies, lipopolysaccharides (LPS)-induced BV2 microglia cells were used and the expression of TLR4, MyD88, p65, and p-p65 in cells was detected by Western blot. ResultsTSPJ treatment significantly alleviated neurological impairment caused by EAE. Histological examination confirmed the protective effects of TSPJ on myelin sheath and the reduction of inflammatory cell infiltration in the brain and spinal cord of EAE mice. TSPJ notably downregulated the ratio of IL-17a/Foxp3 at protein and mRNA levels in CNS, as well as Th17/Treg and Th1/Th2 cell ratios in the spleen of EAE mice. The levels of TNF-α, IL-6, and IL-1β in CNS and peripheral serum also decreased post-TSPJ treatment. In vitro, TSPJ suppressed LPS-induced production of inflammatory factors in BV2 cells via TLR4-MyD88-NF-κB signaling pathway. More importantly, TSPJ interventions altered the composition of gut microbiota and restored the ratio of Firmicutes to Bacteroidetes in EAE mice. Furthermore, Spearman's correlation analysis revealed that a relationship existed between statistically significantly altered genera and CNS inflammatory indices. ConclusionOur results demonstrated TSPJ had therapeutic effects on EAE. Its anti-neuroinflammation property in EAE was related to modulating gut microbiota and inhibiting TLR4-MyD88-NF-κB signaling pathway. Our study indicated that TSPJ may be a potential candidate for the treatment of MS.

Low dosage of prednisone acetate combined with doxycycline in the treatment of chronic endometritis in patients with repeated implantation failure.

To retrospectively investigate whether the oral administration of prednisone acetate with doxycycline increases the cure rate of chronic endometritis (CE) and improves in vitro fertilization (IVF) outcomes in patients with repeated implantation failure (RIF) with CE. In total, 352 patients with RIF were investigated, 128 of whom were diagnosed with CE by hysteroscopy and endometrial immunohistochemical analysis. The patients with CE were divided into CD138-positive high-power field (HPF) counts of 1-2 and ≥3. Forty-five patients were orally administered prednisone acetate tablet 5mg daily and doxycycline 100mg twice daily for 14 consecutive days (group A), and 55 patients were administered doxycycline 100mg orally twice daily for 14 days (group B) and underwent repeated endometrial sampling and histological assessment. Twenty-eight patients (group C) did not receive any treatment. The cure rate of CE and final reproductive outcomes of the frozen-thawed embryo transfer cycle were compared. The total cure rate, cure rate of patients with CE(CD138+ HPF counts: 1-2), and cure rate of patients with CE(CD138+ HPF counts: ≥3) showed no significant difference between groups A and B. Logistics regression analysis indicated that the implantation rate, human chorionic gonadotropin (hCG)-positive rate, clinical pregnancy rate, clinical pregnancy rate with fetal heartbeat on day 30 (D30), and ongoing pregnancy rate was significantly higher in group A than in group C. For CE-cured patients after the treatment, the implantation rate, hCG-positive rate, clinical pregnancy rate, clinical pregnancy rate with fetal heartbeat on D30, and ongoing pregnancy rate were significantly higher in group A than in group B. CE is closely related to RIF occurrence, and the combined oral administration of prednisone acetate and doxycycline can be a treatment option for patients with RIF with CE and improves reproductive outcomes, although it does not improve the CE cure rate compared with doxycycline treatment alone.

Modified Dingchuan Decoction treats cough-variant asthma by suppressing lung inflammation and regulating the lung microbiota.

Modified Dingchuan Decoction (MDD) is a Chinese medicine formula containing 11 materials with cough suppression, asthma relief, and anti-inflammatory effects. This study aimed to evaluate the therapeutic effect of MDD on cough-variant asthma (CVA) and to investigate its mechanism of action. The chemical constituents of MDD were analyzed by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS). A guinea pig CVA model was established using an intramuscular injection of ovalbumin (OVA), combined with an intraperitoneal injection of aluminum hydroxide [Al(OH)3] and nebulized OVA. At the beginning of day 18, the low, medium, and high MDD groups were gavaged with 7.23g/kg, 14.46g/kg, and 28.92g/kg of MDD, respectively, and the positive group was gavaged with 5mg/kg of prednisone acetate combined with 1mg/kg of montelukast sodium; the normal and model groups were given an equal volume of distilled water, once a day for 21 days. The cough was induced by 10-3mol/L capsaicin solution 1h after the last administration, and the number of coughs and the latency of coughs were evaluated. Hematoxylin and eosin staining (H&E) was used to observe pathological changes in the lungs and airways. The concentration of inflammatory factors in bronchoalveolar lavage fluid (BALF) was measured by enzyme-linked immunosorbent assay (ELISA). We analyzed the lung microbiota using 16S ribosomal DNA (16S rDNA) high-throughput sequencing. The 38 chemical components were found in MDD, and MDD reduced the number of coughs in guinea pigs with CVA, prolonged cough latency, improved pathological damage to the lungs and airways, regulated inflammatory factor levels in BALF, and modulated the lung microbiota. This study demonstrated that treating CVA with MDD may be related to inhibiting lung inflammation and regulating lung microbiota.

Intragastric administration of prednisone acetate induced impairment of hippocampal long-term potentiation

Prednisone acetate (PA) has many adverse side effects despite the fact that oral administration of PA is widely administrated in the clinic. However, it is unknown whether PA can cause hippocampal long-term potentiation (LTP) impairment. Therefore, in our study, PA (5 mg/kg·d) through intragastric administration (gavage) was applied to establish a model of impaired hippocampal LTP in C57BL/6 mice, and the method was evaluated by comparing with another method to establish LTP impairment through subcutaneous injection of corticosterone (CORT, 50 mg/kg·d). First, our results showed PA caused a more significant decrease in population spike (PS, %) after high-frequency stimulation (HFS) than CORT, demonstrating PA induced impairment of hippocampal LTP more successfully than CORT. Second, PA caused poorer performance of memory than CORT. Third, PA caused more serious lesions and loss of the granule cell in the dentate gyrus than CORT. Finally, PA caused lower levels of glutamic acid (Glu), N-methyl-d-aspartate receptors (NMDARs) and gamma-aminobutyric acid (GABA) than CORT. All in all, PA (5 mg/kg·d) through intragastric administration (gavage) induced LTP impairment in the hippocampus more successfully than CORT. The neuronal lesions in the dentate gyrus and the consequent decrease of Glu and NMDARs (especially NMDAR2A) may be the cause of LTP impairment.

Prednisone acetate modulates Th1/Th2 and Th17/Treg cell homeostasis in experimental autoimmune uveitis via orchestrating the Notch signaling pathway

Uveitis is an immune eye disease that can seriously impair vision. Glucocorticoids (GCS) have been extensively used to treat uveitis, though the mechanisms have not been fully elucidated. In this study, we investigated the regulatory effects of prednisone acetate (PA) on the Th1/Th2 and Th17/Treg balance in experimental autoimmune uveitis (EAU) through modulating the Notch signaling pathway. Briefly, Lewis rats were randomly divided into the normal control (NC), EAU, and EAU + PA groups. Rats in EAU and EAU + PA groups were induced EAU, while those in the EAU + PA group were treated with PA. Clinical and histopathological scores were employed to assess the progression of EAU. The expression levels of Notch signaling-related molecules (Notch1, Notch2, Dll3, Dll4, and Rbpj) and Th-associated cytokines (IFN-γ, IL-4, IL-10, and IL-17) were assessed via quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). In addition, the frequencies of Th1, Th2, Th17 and Treg cells were detected by flow cytometry. These experimental results indicated that activation of the Notch signaling pathway occurred in EAU rats and resulted in a severe imbalance of the Th17/Treg and Th1/Th2 ratios. PA treatment significantly alleviated ocular inflammation, inhibited activation of the Notch signaling pathway, and declined Th1, and Th17 cell differentiation, thereby restoring the Th1/Th2 and Th17/Treg balance. Collectively, PA can positively enhance the systemic immune response and improve the intraocular microenvironmental homeostasis by inhibiting activation of the Notch signaling pathway and by restoring Th1/Th2 and Th17/Treg balance, thus achieving the goal of treating uveitis.

Novel Monomethoxy Poly(Ethylene Glycol) Modified Hydroxylated Tung Oil for Drug Delivery.

Novel monomethoxy poly(ethylene glycol) (mPEG) modified hydroxylated tung oil (HTO), denoted as mPEG-HTO-mPEG, was designed and synthesized for drug delivery. mPEG-HTO-mPEG consists of a hydroxylated tung oil center joined by two mPEG blocks via a urethane linkage. The properties of mPEG-HTO-mPEG were affected by the length of the mPEG chain. Three mPEG with different molecular weights were used to prepare mPEG-HTO-mPEG. The obtained three mPEG-HTO-mPEG polymers were characterized by nuclear magnetic resonance (NMR), Fourier transformation infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and gel permeation chromatography (GPC), respectively. Furthermore, the particle sizes of mPEG-HTO-mPEG micelles were evaluated by dynamic light scattering (DLS) and transmission electron microscope (TEM). A critical aggregation concentration (CAC) ranged from 7.28 to 11.73 mg/L depending on the chain length of mPEG. The drug loading and release behaviors of mPEG-HTO-mPEG were investigated using prednisone acetate as a model drug, and results indicated that hydrophobic prednisone acetate could be effectively loaded into mPEG-HTO-mPEG micelles and exhibited a long-term sustained release. Moreover, compared with HTO, mPEG-HTO-mPEG had no obvious cytotoxicity to HeLa and L929 cells. Therefore, monomethoxy poly(ethylene glycol) modified hydroxylated tung oil mPEG-HTO-mPEG may be a promising drug carrier.

Epidermis-on-a-chip system to develop skin barrier and melanin mimicking model

In vitro skin models are rapidly developing and have been widely used in various fields as an alternative to traditional animal experiments. However, most traditional static skin models are constructed on Transwell plates without a dynamic three-dimensional (3D) culture microenvironment. Compared with native human and animal skin, such in vitro skin models are not completely biomimetic, especially regarding their thickness and permeability. Therefore, there is an urgent need to develop an automated biomimetic human microphysiological system (MPS), which can be used to construct in vitro skin models and improve bionic performance. In this work, we describe the development of a triple-well microfluidic-based epidermis-on-a-chip (EoC) system, possessing epidermis barrier and melanin-mimicking functions, as well as being semi-solid specimen friendly. The special design of our EoC system allows pasty and semi-solid substances to be effectively utilized in testing, as well as allowing for long-term culturing and imaging. The epidermis in this EoC system is well-differentiated, including basal, spinous, granular, and cornified layers with appropriate epidermis marker (e.g. keratin-10, keratin-14, involucrin, loricrin, and filaggrin) expression levels in corresponding layers. We further demonstrate that this organotypic chip can prevent permeation of over 99.83% of cascade blue (a 607 Da fluorescent molecule), and prednisone acetate (PA) was applied to test percutaneous penetration in the EoC. Finally, we tested the whitening effect of a cosmetic on the proposed EoC, thus demonstrating its efficacy. In summary, we developed a biomimetic EoC system for epidermis recreation, which could potentially serve as a useful tool for skin irritation, permeability, cosmetic evaluation, and drug safety tests.

Pediatric uveitis complicating in cataract formation regained normal visual acuity – a challenging case

Background: Pediatric uveitis and its complications are important causes of child blindness. Strong inflammatory response and unstable treatment compliance result in worse treatment outcome than adults and frequent recurrence. However, effective anti-inflammatory treatment can still lead to good result. Case report: We report a case of pan-uveitis in a 13-year-old patient, complicating in cataract formation who was successfully treated and regained 20/20 final visual acuity. The patient was admitted to us due to blurry vision, pain and redness on her left eye, with best-corrected visual acuity 12/20, intraocular pressure 15 mmHg, ciliary flush, anterior chamber cell and constricted pupil with poor light reflex. Her left eye was diagnosed with anterior uveitis and treated with topical prednisone acetate along with peri-orbital injection of dexamethasone. At 1-week follow-up, her left eye showed significant progress with best-corrected visual acuity being 16/20 and no inflammatory reaction detected. Due to social distancing in Covid-19 pandemic, she was unable to have follow-up examinations; her condition worsened to pan-uveitis which complicated in cataract formation and her visual acuity fell down to counting finger 0.5m. She was then treated with systemic methylprednisolone in 2 weeks and local corticosteroids in 6 months, including 3 consecutive peri-orbital injections of triamcinolone acetate with monthly interval and topical prednisone acetate; after that she underwent cataract surgery with anterior vitreous humor removed and intraocular lens implanted in the ciliary sulcus. At 1-month follow-up, best-correct visual acuity of her left eye was 20/20 and intraocular pressure was 16 mmHg, the inflammatory response of her left eye was completely in control. Conclusion: Effective anti-inflammatory treatment even after surgery (if existed) takes the decisive role in regaining patient’s vision. Cataract removal surgery on pediatric uveitis patients should combine with vitrectomy and the surgeon should be prepared to place the intraocular lens in the ciliary sulcus.