Basiliximab Treatment for Patients With Steroid-Refractory Acute Graft-Versus-Host Disease Following Matched Sibling Donor Hematopoietic Stem Cell Transplantation.

Basiliximab is an important treatment for steroid-refractory acute graft-versus-host disease (SR-aGVHD). We performed this retrospective study to evaluate the efficacy and safety of basiliximab treatment in SR-aGVHD patients following matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) (n = 63). Overall response rate (ORR) was 63.5% and 54% at any time and at day 28 after basiliximab treatment. Grade III-IV aGVHD before basiliximab treatment predicted a poor ORR after basiliximab treatment. The rates of virus, bacteria, and fungi infections were 54%, 23.8%, and 3.1%, respectively. With a median follow-up of 730 (range, 67-3,042) days, the 1-year probability of overall survival and disease-free survival after basiliximab treatment were 58.6% (95% confidence interval [CI] = 47.6%-72.2%) and 55.4% (95% CI = 44.3%-69.2%), respectively. The 3-year cumulative incidence of relapse and non-relapse mortality after basiliximab treatment were 18.9% (95% CI = 8.3%-29.5%) and 33.8% (95% CI = 21.8%-45.7%), respectively. Comorbidities burden before allo-HSCT, severity of aGVHD and liver aGVHD before basiliximab treatment showed negative influences on survival. Thus, basiliximab was safe and effective treatment for SR-aGVHD following MSD-HSCT.

Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis.

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

The effect of steroid therapy on pancreatic exocrine function in autoimmune pancreatitis.

BACKGROUND/OBJECTIVES: Autoimmune pancreatitis (AIP) is a steroid-responsive inflammatory disease of the pancreas. Few studies investigated pancreatic exocrine function (PEF) in patients suffering from AIP and no definitive data are available on the effect of steroids in PEF recovery. Aim of the study is the evaluation of severe pancreatic insufficiency (sPEI) prevalence in AIP at clinical onset and after steroid treatment. METHODS: 312 Patients with diagnosis of AIP between January 1st, 2010 and December 31st, 2020 were identified in our prospectively maintained register. Patients with a pre-steroid treatment dosage of fecal elastase-1 (FE-1) were included. Changes in PEF were evaluated in patients with available pre- and post-treatment FE (between 3 and 12 months after steroid). RESULTS: One-hundred-twenty-four patients were included, with a median FE-1 of 122 (Q1-Q3: 15-379) µg/g at baseline. Fifty-nine (47.6 %) had sPEI (FE-1<100 µg/g). Univariable analysis identified type 1 AIP, radiological involvement of the head of the pancreas (diffuse involvement of the pancreas or focal involvement of the head), weight loss, age and diabetes as associated with a greater risk of sPEI. However, at multivariable analysis, only the involvement of the head of the pancreas was identified as independent risk factor for sPEI. After steroids, mean FE-1 changed from 64 (15-340) to 202 (40-387) µg/g (P = 0.058) and head involvement was the only predictor of improvement of sPEI. CONCLUSION: The inflammatory involvement of the head of the pancreas is associated with PEF severity, as well as PEF improvement after treatment with steroids in patients with AIP.

Design, synthesis and molecular modeling of novel D-ring substituted steroidal 4,5-dihydropyrazole thiazolinone derivatives as anti-inflammatory agents by inhibition of COX-2/iNOS production and down-regulation of NF-κB/MAPKs in LPS-induced RAW264.7 macrophage cells.

It has been reported that 4,5-dihydropyrazole and thiazole derivatives have many biological functions, especially in the aspect of anti-inflammation. According to the strategy of pharmacophore combination, we introduced thiazolinone and dihydropyrazole moiety into steroid skeleton to design and synthesize a novel series of D-ring substituted steroidal 4,5-dihydropyrazole thiazolinone derivatives, and assessed their in vitro anti-inflammatory profiles against Lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells. The anti-inflammatory activities assay demonstrated that compound 12e was considered as the most effective anti-inflammatory drug, which suppressed the expression of pro-inflammatory mediators including nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), it also dose-dependently inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-induced RAW 264.7 macrophage cells. Furthermore, the results of the Western blot analysis showed a correlation between the inhibition of the Nuclear factor-kappa B (NF-κB) and Mitogen-activated protein kinases (MAPKs) signaling pathways and the suppressive effects of compound 12e on pro-inflammatory cytokines. Molecular docking studies of compound 12e into the COX-2 protein receptor (PDB ID: 5IKQ) active site was performed to rationalize their COX-2 inhibitory potency. The results were found to be in line with the biological findings as they exerted more favorable interactions compared to that of dexamethasone (DXM), explaining their remarkable COX-2 inhibitory activity. The findings revealed that these candidates could be identified as potent anti-inflammatory agents, compound 12e could be a promising drug for the treatment of inflammatory diseases.

Combined Ultrasound and Fluoroscopy versus Ultrasound versus Fluoroscopy-Guided Caudal Epidural Steroid Injection for the Treatment of Unilateral Lower Lumbar Radicular Pain: A Retrospective Comparative Study.

Background and Objectives: This study aimed to evaluate the mid-term effectiveness and safety of a combined ultrasound (US) and fluoroscopy (FL)-guided approach in comparison to US-guided and FL-guided caudal epidural steroid injections (CESI) for treating unilateral lower lumbar radicular pain. Materials and Methods: A total of 154 patients who underwent CESI between 2018 and 2022 were included. Patients were categorized into three groups based on the guidance method: combined US and FL (n = 51), US-guided (n = 51), and FL-guided (n = 52). The study design was retrospective case-controlled, utilizing patient charts and standardized forms to assess clinical outcomes, adverse events, complications during the procedures. Results: In all groups, Oswestry Disability Index and Verbal Numeric Scale scores improved at 1, 3, and 6 months after the last injection, with no significant differences between groups (p < 0.05). The treatment success rate at all time points was also similar among the groups. Logistic regression analysis showed that injection method, cause, sex, age, number of injections, and pain duration did not independently predict treatment success. Blood was aspirated before injection in 2% (n = 1), 13.5% (n = 7), and 4% (n = 2) of patients in the combined US and FL groups, FL-guided groups, and US-guided groups, respectively. Intravascular contrast spread was detected in one patient in the combined method groups and seven in the FL-guided groups. Conclusions: When comparing pain reduction and functional improvement, there was no significant difference between the three methods. The combined method took less time compared to using FL alone. The combined approach also showed a lower occurrence of intravascular injection compared to using FL alone. Moreover, blood vessels at the injection site can be identified with an ultrasound using the combined method. Given these advantages, it might be advisable to prioritize the combined US- and FL-guided therapy when administering CESI for patients with unilateral lumbar radicular pain.

Expression and functional analysis of Fushi Tarazu transcription factor 1 (FTZ-F1) in the regulation of steroid hormones during the gonad development of Fujian Oyster, Crassostrea angulata.

Crassostrea angulata, a major shellfish cultivated in Southern China, has experienced a notable surge in commercial value in recent years. Understanding the molecular mechanisms governing their reproductive processes holds significant implications for advancing aquaculture practices. In this study, we cloned the orphan nuclear receptor gene, Fushi Tarazu transcription factor 1 (FTZ-F1), of C. angulata and investigated its functional role in the gonadal development. The full-length cDNA of FTZ-F1 spans 2357 bp and encodes a protein sequence of 530 amino acids. Notably, the amino acid sequence of FTZ-F1 in C. angulata shares remarkable similarity with its homologues in other species, particularly in the DNA-binding region (>90%) and ligand-binding region (>44%). In C. angulata, the highest expression level of FTZ-F1 was observed in the ovary, exhibiting more than a 200-fold increase during the maturation stage compared to the initiation stage (P < 0.001). Specifically, FTZ-F1 was mainly expressed in the follicular cells surrounding the oocytes of C. angulata. Upon inhibiting FTZ-F1 gene expression in C. angulata through RNA interference (RNAi), a substantial reduction in the expression of genes involved in the synthesis of sex steroids in the gonads, including 3ß-HSD, Cyp17, and follistatin, was observed. In addition, estradiol (E2) and testosterone (T) levels also showed a decrease upon FTZ-F1 silencing, resulting in a delayed gonadal development. These results indicate that FTZ-F1 acts as a steroidogenic factor, participating in the synthesis and regulation of steroid hormones and thus playing an important role in the reproductive and endocrine systems within oysters.

Preoperative laboratory measurements as a predictor for nasal steroid irrigations after sinus surgery for chronic rhinosinusitis with nasal polyps.

PURPOSE: To assess whether preoperative C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), immunoglobulin E (IgE), and blood eosinophil percentage (EOS) can predict need for steroid irrigations after FESS. MATERIALS AND METHODS: Adult patients at BIDMC from inception until September 8, 2023 with chronic rhinosinusitis with nasal polyps who underwent FESS and had preoperative CRP (n = 129), ESR (n = 79), IgE (n = 107), or EOS (n = 125) were included. Labs were divided into normal (CRP: 0-5.0 mg/L; ESR: 0-15 mm/h; IgE: 150-300Ul/mL; EOS: 1-7 %) and high groups (CRP: >5.0 mg/L; ESR: >15 mm/h; IgE: >300Ul/mL; EOS: >7 %). The primary outcome was need for intranasal steroid irrigations after FESS (≤4 weeks, 4-12 weeks, 12-26 weeks, 26-52 weeks, 1-3 years, 3-5 years, and > 5 years). Receiver operating characteristic curves were created to determine thresholds for predicting postoperative steroid irrigations. RESULTS: Elevated IgE required intranasal steroid irrigation at 1-3 years (normal 34 %, high 62 %, p = 0.02), 3-5 years (normal 24 %, high 48 %, p = 0.04), and > 5 years (normal 19 %, high 43 %, p = 0.02). Elevated EOS required intranasal steroid irrigation at 26-52 weeks (normal 7 %, high 25 %, p = 0.009) and > 5 years (normal 19 %, high 46 %, p = 0.005). The area under the curve for IgE at 1-3 years was 0.696 (95 % CI: 0.597-0.795) with cutoff at 144-148 Ul/mL. CRP and ESR were not predictive of postoperative intranasal steroid treatment. CONCLUSIONS: Elevated IgE and EOS (but not CRP or ESR) may predict need for intranasal steroid treatment after FESS.

Unintentional Injection Into the Retrodural Space of Okada During Transforaminal Epidural Steroid Injection.

BACKGROUND: Transforaminal epidural steroid injection (TFESI) is commonly used for radicular pain, but can lead to an unintentional injection into the retrodural Space of Okada (RSO), an extradural space located dorsal to the ligamentum flavum, instead of the epidural space. OBJECTIVES: To determine the prevalence and describe the fluoroscopic imaging features of an unintentional injection into the RSO during a TFESI and to review the history of injections into the RSO. STUDY DESIGN: Observational study and original research. SETTING: This work was conducted at Jeju National University School of Medicine, Jeju, Republic of Korea. METHODS: A total of 5,429 lumbar TFESIs performed from the September 1, 2018 through October 31, 2021 were analyzed for unintentional RSO injections using fluoroscopic-guided contrast medium patterns. RESULTS: The rate of unintentional injection into the RSO was 0.20% (11 incidents). Contrast medium patterns in the RSO had a sigmoid or ovoid shape confined to the affected facet joint, or a butterfly-shaped pattern extending into the contralateral facet joint, but rarely extending beyond the upper or lower level. LIMITATION: The rarity of unintentional injection into the RSO prevented a randomized controlled study design. CONCLUSIONS: Careful fluoroscopic examination of contrast medium patterns during lumbar TFESI is crucial to identify needle placement in the RSO. If detected, the procedure can be corrected by slightly advancing the needle into the foramen.

Steroidal epoxides as anticancer agents in lung, prostate and breast cancers: The case of 1,2-epoxysteroids.

Cancer continues to be a serious threat to human health worldwide. Lung, prostate and triple-negative breast cancers are amongst the most incident and deadliest cancers. Steroidal compounds are one of the most diversified therapeutic classes of compounds and they were proven to be efficient against several types of cancer. The epoxide function has been frequently associated with anticancer activity, particularly the 1,2-epoxide function. For this reason, three 1,2-epoxysteroid derivatives previously synthesised (EP1, EP2 and EP3) and one synthesised for the first time (oxysteride) were evaluated against H1299 (lung), PC3 (prostate) and HCC1806 (triple-negative breast) cancer cell lines. A human non-tumour cell line, MRC-5 (normal lung cell line) was also used. EP2 was the most active compound in all cell lines with IC50 values of 2.50, 3.67 and 1.95 µM, followed by EP3 with IC50 values of 12.65, 15.10 and 14.16 µM in H1299, PC3 and HCC1806 cells, respectively. Additional studies demonstrated that EP2 and EP3 induced cell death by apoptosis at lower doses and apoptosis/necrosis at higher doses, proving that their effects were dose-dependent. Both compounds also exerted their cytotoxicity by ROS production and by inducing double-strand breaks. Furthermore, EP2 and EP3 proved to be much less toxic against a normal lung cell line, MRC5, indicating that both compounds might be selective, and they also demonstrated suitable in silico ADME and toxicity parameters. Finally, none of the compounds induced haemoglobin release. Altogether, these results point out the extreme relevance of both compounds, especially EP2, in the potential treatment of these types of cancer.

Development of new steroid-based hydrazide and (thio)semicarbazone compounds with anticancer properties.

Most breast and prostate cancers are caused by abnormal production or action of steroidal hormones. Hormonal drugs based on steroid scaffolds represent a significant class of chemotherapeutics that are routinely used in chemotherapy. In this study, the synthesis of new 17a-homo lactone and 17α-(pyridine-2-ylmethyl) androstane derivatives with hydrazide and semicarbazone motifs is presented. All compounds were screened for their effect on cell viability against a panel of five cancer cell lines and one healthy cell line. Two compounds showed significant cytotoxicity against cancer cells, with low toxicity against healthy cells. The relative binding affinities of compounds for the ligand-binding domains of estrogen receptor α, estrogen receptor ß, androgen receptor and glucocorticoid receptor were tested using a fluorescence screen in yeast. Potential for inhibition of aldo-keto reductase 1C3 and 1C4 activity was measured in vitro. Experimental results are analyzed in the context of molecular docking simulations. Our results could help guide design of steroid compounds with improved anticancer properties against androgen- and estrogen-dependent cancers.

Comparison of greater occipital nerve blockade with radiofrequency and steroid in chronic migraine.

OBJECTIVES: The study aims to retrospectively compare steroid and radiofrequency treatments for the greater occipital nerve(GON) under ultrasound guidance in chronic migraine. METHODS: Monthly average headache attack frequency, attack duration, visual analog scale(VAS) and the number of days analgesics were taken were recorded. Under ultrasound guidance, GON block was administered once a week for a total of four sessions. In the final session, 4 mg of dexamethasone was added to the local anesthetic for the steroid group (n:26). Pulsed radiofrequency (RF) treatment was applied to the RF group (n:25) just before the last session of the GON block. The pain course in the week following the procedure monthly average headache attack frequency, attack duration, VAS and the number of days analgesics were taken in a month were compared for both groups at 1-3-6 months. RESULTS: In the first month, a statistically significant decrease in attack frequency was observed in the RF group. However, no statistically significant differences were found between the groups in other findings at different time intervals. A significant decrease headache attack duration,VAS, and the number of days analgesics were taken in a month was observed in both treatment groups. Both treatments were found to be effective, but the effect size of the treatment was higher in the RF group compared to the steroid group. CONCLUSION: Although the results were better in the group receiving pulsed RF treatment, except for the attack frequency in the first month, no statistically significant superiority of one treatment method over the other was determined.

Cevanine-type steroidal alkaloids from the bulbs of Fritillaria cirrhosa D. Don.

Eight previously undescribed cevanine-type steroidal alkaloids, cirrhosinones I-N and cirrhosinols A-B, along with five known analogs, were isolated from the bulbs of Fritillaria cirrhosa D. Don. Their structures were elucidated on the basis of comprehensive analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and single-crystal X-ray diffraction analyses. All compounds revealed weak NO inhibitory activities in the LPS-stimulated NR8383 cells at the concentration of 20 µM, with inhibition ratios ranging from 5.1% to 14.3%.

Role of procalcitonin, interleukin-6 and interleukin-10 as a predictive marker for the use of perioperative steroid in maxillofacial trauma patients.

Maxillofacial trauma often brings significant challenges for surgeons in terms of preoperative oedema. Steroids offer oedema reduction, yet potentially increase the risks of postoperative infection. This study explores procalcitonin (PCT), as a marker for bacterial infection risk, and interleukins IL-6 and IL-10, which respectively signify pro-inflammatory and anti-inflammatory responses, as potential indicators of infection and inflammation in these trauma cases and thereby aid in refining perioperative guidelines for the use of steroids. A prospective study was conducted at a tertiary public hospital in India from 2019 to 2022 on patients >18 years with facial trauma. After specific exclusions, patients were randomised into steroid (Group A) and non-steroid (Group B) groups. Various parameters including oedema, PCT, IL-6, and IL-10 levels were measured and analysed using SPSS software. Out of 80 patients, 44 were in Group A and 36 in Group B. Post-24 hours, Group A showed significant oedema reduction, with 25 patients displaying a decline to mild oedema, versus 10 patients in Group B (p = 0.034). However, Group A witnessed a higher infection risk, with 20 patients showing positive wound cultures versus three in Group B. Subgroup analysis revealed a link between higher PCT levels and infections (p = 0.039). Additionally, Group A showed less intraoperative bleeding and reduced operating time. While perioperative steroids mitigate swelling, they might increase postoperative infection risk. Elevated PCT levels indicate potential wound infections, suggesting those patients should avoid perioperative steroids. IL-6 and IL-10 trends during perioperative phases can predict pronounced oedema outcomes.

Inhibition of protein misfolding and aggregation by steroidal quinoxalin-2(1H)-one and their molecular docking studies.

A series of D-ring fused 16-substituted steroidal quinoxalin-2(1H)-one attached to an electron-releasing (ER) or electron-withdrawing (EW) groups via steroidal oxoacetate intermediate were synthesized to investigate their protein aggregation inhibition potential using human lysozyme (HLZ). The influence of the type of substituent at the C-6 positions of the quinoxalin-2(1H)-one ring on the protein aggregation inhibition potential was observed, showing that the EW moiety improved the protein aggregation inhibition potency. Of all the evaluated compounds, NO2-substituted quinoxalin-2(1H)-one derivative 13 was the most active compound and had a maximum protein aggregation inhibition effect. Significant stabilization effects strongly support the binding of the most biologically active steroidal quinoxalin-2(1H)-one with docking studies. The predicted physicochemical and ADME properties lie within a drug-like space which shows no violation of Lipinski's rule of five except compounds 12 and 13. Combined, our results suggest that D-ring fused 16-substituted steroidal quinoxalin-2(1H)-one has the potential to modulate the protein aggregation inhibition effect.

Bioinformatics analysis of PANoptosis regulators in the diagnosis and subtyping of steroid-induced osteonecrosis of the femoral head.

In this study, we aimed to investigate the involvement of PANoptosis, a form of regulated cell death, in the development of steroid-induced osteonecrosis of the femoral head (SONFH). The underlying pathogenesis of PANoptosis in SONFH remains unclear. To address this, we employed bioinformatics approaches to analyze the key genes associated with PANoptosis. Our analysis was based on the GSE123568 dataset, allowing us to investigate both the expression profiles of PANoptosis-related genes (PRGs) and the immune profiles in SONFHallowing us to investigate the expression profiles of PRGs as well as the immune profiles in SONFH. We conducted cluster classification based on PRGs and assessed immune cell infiltration. Additionally, we used the weighted gene co-expression network analysis (WGCNA) algorithm to identify cluster-specific hub genes. Furthermore, we developed an optimal machine learning model to identify the key predictive genes responsible for SONFH progression. We also constructed a nomogram model with high predictive accuracy for assessing risk factors in SONFH patients, and validated the model using external data (area under the curve; AUC = 1.000). Furthermore, we identified potential drug targets for SONFH through the Coremine medical database. Using the optimal machine learning model, we found that 2 PRGs, CASP1 and MLKL, were significantly correlated with the key predictive genes and exhibited higher expression levels in SONFH. Our analysis revealed the existence of 2 distinct PANoptosis molecular subtypes (C1 and C2) within SONFH. Importantly, we observed significant variations in the distribution of immune cells across these subtypes, with C2 displaying higher levels of immune cell infiltration. Gene set variation analysis indicated that C2 was closely associated with multiple immune responses. In conclusion, our study sheds light on the intricate relationship between PANoptosis and SONFH. We successfully developed a risk predictive model for SONFH patients and different SONFH subtypes. These findings enhance our understanding of the pathogenesis of SONFH and offer potential insights into therapeutic strategies.

Biochar-based polymeric film as sustainable and efficient sorptive phase for preconcentration of steroid hormones in environmental waters and wastewaters.

BACKGROUND: The environmental impact of sample preparation should be minimized through simplification of the procedures and the use of natural, renewable and/or reusable materials. In such scenario, thin-film microextraction fulfils the former criteria, as it enables few steps and miniaturization, thus small amount of extraction phase. At the same time, the use of sorbents such as biochars obtained from biomass waste is even more promoted due to their availability at low cost and increased life-cycle in a circular economy vision. However, it is not always easy to combine these criteria in sample preparation. RESULTS: A thin film microextraction was developed for the determination of steroids in aqueous samples, entailing a membrane made of cellulose triacetate and a wood-derived biochar (Nuchar®) as carbon precursor. Different characterization techniques showed the successful preparation, whereas the sorption kinetics experiments demonstrated that biochar is responsible for the extraction with the polymer acting as a smart support. After a study about membranes' composition in terms of biochar amounts (4 %, 10 %, 16 % wt) and type of synthesis set up, the ceramic 3D-mold was selected, achieving reproducible and ready-to-use membranes with composition fixed as 10 %. Different elution conditions, viz. type and time of agitation, type, composition and volume of eluent, were evaluated. The final microextraction followed by HPLC-MS/MS quantification was successfully validated in river and wastewater treatment plant effluent samples in terms of accuracy (R% 64-123 %, RSD<19 % in river; R% 61-118 %, RSD <18 % in effluent, n = 4), sensitivity (MQLs 0.2-8.5 ng L-1) and robustness. SIGNIFICANCE: This novel biochar-based polymeric film proved to be a valid and sustainable sorbent, in terms of extraction capability, ease of preparation and greenness. By comparison with literature and the greenness evaluation with the most recent metric tools, this method expands the potential applicability of the thin-film microextraction and opens up innovative scenarios for sustainable procedures entailing the use of biochars entrapped in bio-polymers.