Steroidal Drugs Research Articles

A highly efficient mixed strain fermentation strategy to produce 11α-Hydroxyandrost-4-ene-3,17-dione from phytosterols.

11α-Hydroxyandrost-4-ene-3,17-dione (11α-OH AD) is an essential steroid hormone drug intermediate that exhibits low biotransformation efficiency. In this study, a mixed-strain fermentation strategy was established for the efficient production of 11α-OH AD from phytosterols (PS). Initially, strains were screened for efficient transformation of AD to produce 11α-OH AD. Subsequently, a dual-strain mixed-culture fermentation technique was established, with Mycolicibacterium neoaurum CICC 21097 ΔksdD (MNR) showing highly effective results. Ultimately, a one-step conversion process for the production of 11α-OH AD was achieved at a molar yield of 76.5% under optimal conditions using PS as a substrate, the highest reported yield to date. Additionally, studies revealed synergistic metabolic interactions between MNR and Aspergillus ochraceus in the mixed-culture system. These findings provide valuable insights for the industrial production of high-value products using mixed-strain fermentation.

Engineering a two-enzyme system in Mycolicibacterium neoaurum for efficient biotransformation of phytosterols to dihydrotestosterone.

Dihydrotestosterone (DHT) is a valuable steroid drug with widespread clinical applications, but traditional chemical synthesis is environmentally harmful and requires complex reaction conditions. This study introduces a one-step microbial transformation method for the production of DHT from inexpensive phytosterols (PS) using engineered Mycolicibacterium neoaurum (MNR). The heterologous expression of 5α-reductase (5α-R) and 17β-hydroxysteroid dehydrogenase (17β-HSD) in MNR enabled the efficient conversion of PS to DHT. To further enhance 5α-R activity, semi-rational mutagenesis was employed, which significantly increasing DHT production. Molecular dynamics simulations provided insights into the underlying mechanisms driving this enhancement. Additionally, the incorporation of a PntAB-based NADPH regeneration system further improved DHT yield. Process optimization resulted in a maximum DHT concentration of 1.123g·L-1, representing the first gram-scale microbial production of DHT. Compared to traditional chemical synthesis, this biotransformation method offers milder reaction conditions, reduced environmental impact, and eliminates the need for toxic catalysts. This work demonstrates a sustainable and efficient microbial method for DHT production, with significant industrial potential for the greener manufacturing of steroid hormone drugs.

An Effectiveness Test Combination of Ethanol Extracts of Buas-buas Leaves (Premna serratifolia L.) and Sappan Wood (Caesalpinia sappan L.) as Topical Antiinflammatory Agent in Male White Rats (Rattus novergicus)

Background: Inflammation is the reaction of the immune system to tissue damage resulting from physical injury, harmful chemicals, or microbial agents. Steroid and non-steroid drugs are commonly used to treat inflammation, but long-term use can result in side effects, such as hormonal disorders and gastric ulcers. Buas-buas leaves and sappan wood has potential as traditional medicines, and based on empirical evidence, they utilize both plants as anti-inflammatory, antibacterial, antioxidant, antiallergic, and antiarthritic agents, as well as for the treatment of cardiovascular disorders, cough, and leprosy. Objective: This study aimed to evaluate the effect of combining 96% ethanol extracts from buas-buas leaves and sappan wood to deliver topical anti-inflammatory benefits. Methods: This research was experimental, using thirty male rats divided into six treatment groups: a negative control group with 2% carrageenan, Biocream® control group, a positive control group with Hydrocortisone Acetate, and three treatment groups receiving a combination of ethanol extracts from buas-buas leaves and sappan wood at concentrations of 1.67%, 2.5%, and 3.75%. The test compounds were administered after carrageenan injection. Measurement of skinfold thickness on the backs of the rats was conducted every hour for 6 h using digital calipers, and the difference in skinfold thickness of each rat, AUC value, and percentage of inflammation inhibition was calculated. Data analysis involved the Kolmogorov-Smirnov test and Levene's test to assess normality and homogeneity, respectively, and was subsequently followed by One-way ANOVA and a post-hoc test. Conclusion: The combination of ethanol extracts of Buas-Buas leaves and sappan wood can provide a topical anti-inflammatory effect, with the most effective concentration being 3.75% and an inflammation inhibition percentage of 32.77%.

Functional Expression and Construction of a Self-Sufficient Cytochrome P450 Chimera for Efficient Steroidal C14α Hydroxylation in Escherichia coli.

C14-functionalized steroids enabled diverse biological activities in anti-gonadotropin and anticancer therapy. However, access to C14-functionalized steroids was impeded by the deficiency of chemical synthetic methods. Recently, several membrane-bound fungal cytochrome P450s (CYPs) have been identified with steroid C14α-hydroxylation activity. However, the lack of efficient heterologous overexpression strategy hampered their further characterization and molecular engineering. In the present study, sequences of fungi-derived CYP genes encoding putative 14α-hydroxylase were selected and bioinformatically analyzed. Substitution of the N-terminal hydrophobic helix by a soluble maltose binding protein tag significantly enhanced the soluble expression level in Escherichia coli. A novel CYP originated from Bipolaris oryzae was discovered with high steroidal C14α-hydroxylation activity when coupled with the redox partner CPRlun. A catalytically self-sufficient chimeric CYP-CPR was built by intramolecular fusion, and the electronic transfer rate was improved. A coenzyme NADPH regeneration system was finally constructed by the co-expression of glucose dehydrogenase. The developed soluble multi-enzyme cascade biotransformation system supported the selective C14α-hydroxylation toward progesterone with a final titer of 34.54 mg/L, the highest level achieved in E. coli-based heterologous expression system. This study provides insightful ideas on the functional expression of fungi-derived CYPs and promises an efficient C14α-hydroxylation system for steroidal drugs through protein engineering.

Exosome-delivered NR2F1-AS1 and NR2F1 drive phenotypic transition from dormancy to proliferation in treatment-resistant prostate cancer via stabilizing hormonal receptors

Cancer cells acquire the ability to reprogram their phenotype in response to targeted therapies, yet the transition from dormancy to proliferation in drug-resistant cancers remains poorly understood. In prostate cancer, we utilized high-plasticity mouse models and enzalutamide-resistant (ENZ-R) cellular models to elucidate NR2F1 as a key factor in lineage transition and ENZ resistance. Depletion of NR2F1 drives ENZ-R cells into a relative dormancy state, characterized by reduced proliferation and heightened drug resistance, while NR2F1 overexpression yields contrasting outcomes. Transcriptional sequencing analysis of NR2F1-silenced prostate cancer cells and tissues from the Cancer Genome Atlas-prostate cancer and SU2C cohorts indicated exosomes as the most enriched cell component, with pathways implicated in steroid hormone biosynthesis and drug metabolism. Moreover, NR2F1-AS1 forms a complex with SRSF1 to upregulate NR2F1 expression, facilitating its binding with ESR1 to sustain hormonal receptor expression and enhance proliferation in ENZ-R cells. Furthermore, HnRNPA2B1 interacts with NR2F1 and NR2F1-AS1, assisting their packaging into exosomes, wherein exosomal NR2F1 and NR2F1-AS1 promote the proliferation of dormant ENZ-R cells. Our works offer novel insights into the reawaking of dormant drug-resistant cancer cells governed by NR2F1 upregulation triggered by exosome-derived NR2F1-AS1 and NR2F1, suggesting therapeutic potential for phenotype reversal.Graphical

Enhancement of the Degradation of Phytosterol Side Chains in Mycolicibacterium by Eliminating the Redox Sensitivity of Key Thiolase and Augmenting Cell Activity

Androstenedione (AD) is a vital intermediate in the synthesis of steroid drugs, making its efficient production critical in the steroid drug industry. Acetyl-CoA acetyltransferase (FadA5), a thiolase enzyme, plays an important role in the metabolic process of degrading phytosterol side chains in Mycolicibacterium to produce AD. This work is the first systematic analysis of the role of FadA5 in the transformation of phytosterols by Mycolicibacterium to produce AD. The relationship between redox potential and AD production was examined using resting cells, and it was confirmed that FadA5 is a key enzyme for AD production. Mutating the 87th cysteine of FadA5 to alanine reduced its redox effect, enhancing the substrate tolerance and biotransformation capacity of the strain. Co-expressing Vitreoscilla hemoglobin (VHb) and propionyl-CoA metabolized the transcription activator (PrpR), decreased intracellular reactive oxygen species levels, and improved cell viability. The AD yield of MSP-fA5C87A-VP/ΔfA5 was 2.541 g/L, an increase of 16.83% over the control strain. Using a repeated batch fermentation process, the production efficiency of the MSP-fA5C87A-VP/ΔfA5 strain was 0.658 g/L/d, which was 1.82 times higher than that of the control strain. These findings provide a theoretical basis for understanding and regulating steroid side-chain catabolism in Mycolicibacterium and offer support for the rational modification of industrial strains for steroidal drug precursor production.

Effect of Ginger Oil Massage on Joint Pain among Elderly Inmates of Old Age Home: A Quasi-experimental Study

Introduction: Joint pain is widespread among elderly and is usually accompanied by stiffness that increases with daily activities. Ginger has been found to have similar properties to Non Steroidal Antii-inflammatory Drugs (NSAIDs) in reducing pain and inflammation associated with musculoskeletal conditions. Aim: To investigate the effect of ginger oil massage on joint pain in elderly inmates in old age homes. Materials and Methods: The study adopted a quasiexperimental one-group pretest post-test design and the study was conducted in the old age home Bengaluru, Karnataka, India, from October 2020 to April 2021. Purposive sampling technique was used to select 30 inmates of an old age home located in Bangalore and having joint pain with a score of >1 on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale. The demographic proforma and the WOMAC were used to collect the data. A skin test was performed, to check for any sensitivity reactions and massage using ginger essential oil diluted in coconut oil was administered on the knee joint on alternate days, for six sessions extending over a period of two weeks. The post-test was assessed after third and final (6th) session of massage. Repeated Measures (RM) Analysis of Variance (ANOVA) was computed to determine the difference in pre and post-test WOMAC scores and a significance level of p<0.05 and a confidence interval of 95% was considered to indicate a statistically significant difference. Results: The mean age of the elderly was 69.500±7.505 years with a range 61-82 years. Repeated measure ANOVA demonstrated a significant difference in the second (13.10±5.38) and first post-test WOMAC scores (14.10±6.19) compared to the mean pretest WOMAC score (37.97±12.83) (F=121.14, p<0.001), indicating that ginger oil massage was effective in reducing joint pain among the elderly. Conclusion: Ginger oil massage resulted in the reduction of knee pain and joint stiffness among elderly and therefore, can be a used as an alternative therapy for the elderly with joint pain.

Synthesis of novel estradiol bisselenocyanate with unique 2-selenocyano-17-selenocyanoesteryl structure and evaluation of antitumor activity.

Cancer is one of the most significant diseases that afflict human beings. The pursuit of high efficacy and low-toxicity anticancer drugs has always been a paramount research objective for scientists. In the present study, we incorporated two selenocyano pharmacophores into the 2-site and 17-branch chain of the steroid nucleus in various manners, utilizing estradiol as the fundamental framework. Consequently, several estradiol bisselenocyanate compounds with a 2-selenocyano-17-selenocyanoester structure were synthesized. When compared to the positive control steroidal anti-tumor drug 2-methoxyestradiol, certain derivatives exhibited superior inhibitory activity against tumor cells in vitro, surpassing their monoselenocyanate precursors. The representative compound 4b induced programmed apoptosis in HeLa cells in a concentration-dependent manner during apoptosis and cell cycle experiments, while causing G2 phase arrest predominantly in the cell cycle. Moreover, compound 4b exhibited significant inhibitory effects on cell migration and demonstrated remarkable inhibitory activity against HeLa xenograft tumors in zebrafish models. These findings suggest that these compounds hold potential as promising candidates for anti-tumor drugs and warrant further investigation.

Effect of TetR Family Transcriptional Regulator PccD on Phytosterol Metabolism of Mycolicibacterium.

Androstenedione (AD) is an important intermediate for the production of steroidal drugs. The process of transforming phytosterols into AD by Mycolicibacterium is mainly the degradation process of the phytosterol side chain, and the excessive accumulation of propionyl-CoA produced by Mycobacterium will produce toxic effects, which seriously restricts the transformation performance of strains. In this study, Mycolicibacterium sp. LZ2 (Msp) was used as the research object to study the transcription factor PccD of the TetR family, which has the role of propionyl-CoA metabolism regulation. By constructing overexpression and deletion strains of pccD, it was confirmed that pccD had an inhibitory effect on the transcription of propionyl-CoA carboxylase genes (pccA and pccB). Electrophoretic Mobility Shift Assay (EMSA) and DNase I footprint analysis demonstrated that PccD is directly involved in the transcriptional regulation of pccA and pccB and is a negative transcriptional regulator of the pcc operon. In the study of phytosterol transformation, the growth rate and bacterial viability of Msp-ΔpccD were higher than Msp, but the growth of Msp-pccD was inhibited. As a result of testing of intracellular propionyl-CoA levels and AD production yields, it was found that lower propionyl-CoA levels and higher AD production yields were observed in Msp-ΔpccD. The results expand the cognition of propionyl-CoA metabolism regulation and provide a theoretical basis and reference for the rational transformation of phytosterol transformation strains and secondary metabolite synthesis strains with propionyl-CoA as a substrate, which has important research significance.

NOVEL HYBRIDS OF QUINOLINE LINKED PYRIMIDINE DERIVATIVES AS CYCLOOXYGENASE INHIBITORS: MOLECULAR DOCKING, ADMET STUDY, AND MD SIMULATION

Objective: Finding novel anti-inflammatory compounds is a crucial sector of research despite the significant advances this field has made. Inefficiency and unfavorable side effects are indeed potential drawbacks of conventional therapy utilizing steroidal or nonsteroidal drugs. This study aims to screen the designed quinoline-linked pyrimidine derivatives as Cyclooxygenase (COX) inhibitors. Methods: In the present study, we assessed the binding interactions of designed quinoline-linked pyrimidine derivatives with COX enzymes using a molecular docking approach. Using Molecular Dynamics (MD) simulations, the compound’s behavior was further investigated and its stability and conformational dynamics were demonstrated. Schrödinger's QikProp program was utilized to analyze the Absorption, Distribution, Metabolism, and Excretion (ADME) properties and toxicity properties were further investigated using Osiris Property Explorer. Additionally, the protein-ligand complexes' binding free energy has been ascertained using the Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) approach, which offered crucial information regarding the strength of their interactions. Results: The designed quinoline-linked pyrimidine derivatives fulfilled the Lipinski Rule of Five and had physicochemical characteristics within acceptable ranges, better ADME properties, and were non-toxic. Among the designed compounds, QPDU1 and QPDT6 showed correspondingly good docking scores for COX-1 and COX-2. QPDT6 was additionally analyzed by MD simulation studies to thoroughly examine the interaction between protein and ligand and their stability. Conclusion: The proposed compounds exhibit strong binding affinities to COX enzymes, stable interactions in MD simulations, and favorable drug-like features. These results support the need for more research and development of these substances as possible anti-inflammatory drugs.

Modification of B-Nor Steroids Mediated by Filamentous Fungus Fusarium culmorum: Focus on 15α-Hydroxylase Activity.

The metabolic activities of microorganisms to modify the chemical structures of organic compounds are an effective tool for the production of high-value steroidal drugs or active pharmaceutical ingredients (APIs). The integration of biotransformation into the synthesis of APIs can greatly reduce the number of reaction steps and achieve higher process efficiency, thus enabling their greener production. The current research efforts are focused on either the optimization of existing processes or identification of new potentially useful bioconversions. This study aimed to assess the catalytic abilities of the filamentous fungus Fusarium culmorum AM 282 to transform B-nor analogues (5(6→7)abeo compounds) of steroid hormones: androstenedione (AD), dehydroepiandrosterone (DHEA) and its acetate. Our previous studies have demonstrated that this strain is an active hydroxylating catalyst for many steroidal compounds with diverse structures. The results presented in this work showed that the hydroxylation of B-nor steroids occurred with the regio- and stereoselectivity typical of this strain in relation to the corresponding natural hormones of the standard 6:6 A/B series. After the transformations of B-nor-DHEA and its acetate, 15α-hydroxy-B-nor-DHEA was obtained as the sole product of the reaction, while the transformation of the AD analogue resulted in a mixture of its 15α- and 6α-hydroxy derivatives. A detailed analysis of the transformation course indicated that all the obtained hydroxy derivatives could be the result of the activity of the same enzyme. The presented results may provide a basis for research aimed at understanding the molecular nature of cytochrome P-450 monooxygenase from F. culmorum AM 282 with its ability for 15α-hydroxylation of steroidal compounds. An analysis of the pharmacokinetic and pharmacodynamic properties of the obtained metabolites with cheminformatics tools suggests their potential biological activity.

The Challenges of Local Intra-Articular Therapy.

Fibroblast-like synoviocytes (FLSs) are among the main disease-driving players in most cases of monoarthritis (MonoA), oligoarthritis, and polyarthritis. In this review, we look at the characteristics and therapeutic challenges at the onset of arthritis and during follow-up management. In some cases, these forms of arthritis develop into autoimmune polyarthritis, such as rheumatoid arthritis (RA), whereas local eradication of the RA synovium could still be combined with systemic treatment using immunosuppressive agents. Currently, the outcomes of local synovectomies are well studied; however, there is still a lack of a comprehensive analysis of current local intra-articular treatments highlighting their advantages and disadvantages. Therefore, the aim of this study is to review local intra-articular therapy strategies. According to publications from the last decade on clinical studies focused on intra-articular treatment with anti-inflammatory molecules, a range of novel slow-acting forms of steroidal drugs for the local treatment of synovitis have been investigated. As pain is an essential symptom, caused by both inflammation and cartilage damage, various molecules acting on pain receptors are being investigated in clinical trials as potential targets for local intra-articular treatment. We also overview the new targets for local treatment, including surface markers and intracellular proteins, non-coding ribonucleic acids (RNAs), etc.

Comparison of Outcomes of Bell’s Palsy Patients Treated with Steroid and Steroid with Antiviral Drug in a Tertiary Care Hospital

Background: Bell’s palsy is the most common acute mononeuropathy associated with idiopathic unilateral facial weakness, characterized by facial asymmetry. Though steroids have effectiveness in managing Bell’s palsy, the use of antiviral is still debatable. Objective: To compare the outcome of Bell’s palsy with treatment by steroid versus combination of steroid and antiviral drugs. Methodology: A prospective analytical study was performed on 84 patients with acute Bell’s palsy attending at Neurology outpatient department of Mymensingh Medical College Hospital from July 2014 to June 2016. The patients were divided into two groups purposively after initial assessment as per House-Brackmann grading system (HBS). Group-I patients were treated with oral prednisolone and oral valacyclovir and Group-II patients were treated with oral prednisolone only. Both groups received facial exercises as per demonstration and proper eye care throughout the study period. Follow-up was done after 2 weeks, 4 weeks and 3 months for collection of data about recovery according to reassessment. Results: The analysis revealed that recovery rates at all 3 follow-ups were higher in the combination group than that of the prednisolone-only group [29(67.44%) versus 18 (43.90%) at 2nd week follow-up, 35(81.39%) versus 25(60.97%) at 4th week follow up and 40 (93.02%) versus 30(73.17%) at 3rd month follow-up]. Moreover, the expected recovery rate was higher in severe Bell’s palsy patients in the combination group than in steroid-alone group (22, 88.0% complete recovery versus 13, 54.17% complete recovery at the end of 3 months of treatment) [p=0.034]. haemorrhagic shock, spinal cord damage, septic shock and crush syndrome. Conclusion: The study showed antiviral (valacyclovir) plus steroid (prednisolone) to be more effective than steroid (prednisolone) alone in the treatment of Bell’s palsy. Moreover, outcome was more favorable in combination groups presenting with severe disease. Lessen their severity. Journal of Monno Medical College December, 2023; 9 (2):58-62

Neglected Pulmonary Infection Caused by Exophiala dermatitidis Misidentified as Rhodotorula spp.

Exophiala dermatitidis is an emerging black fungus that causes pulmonary infections that may be underestimated by conventional culture methods. We encountered one case that initially appeared to be yeast and was misidentified as Rhodotorula spp. using a commercial identification kit. Thus, genetic identification and clinical background investigations were conducted on 46 strains of Rhodotorula spp. The sequences of the internal transcribed spacer and large-subunit RNA genes (D1/D2 regions) of 43 isolates, excluding two environmental isolates and one difficult-to-culture isolate, were determined and genetically identified. Notably, 22 isolates were identified as E. dermatitidis and misidentified as Rhodotorula spp. using the conventional method. Based on the exclusion criteria, the clinical information of 11 patients was retrospectively reviewed. Five cases (definite) had definite exacerbation of pulmonary infections due to E. dermatitidis, and six cases (possible) had undeniable infections. Of the 11 cases of pulmonary infection suggested to be caused by E. dermatitidis, comorbidities included two cases of chronic pulmonary aspergillosis (CPA), three cases of pulmonary non-tuberculous mycobacterial (NTM) infection and one case of pulmonary nocardiosis, suggesting a trend towards simultaneous detection of chronic pulmonary infections. Steroid and immunosuppressive drug use was observed in five cases, and β-D-glucan elevation was observed in three of five definite cases of pulmonary infections due to E. dermatitidis. The possibility of E. dermatitidis infection should be considered when Rhodotorula spp. are isolated from cultures of airway-derived specimens, and, in addition to CPA and NTM, identification of E. dermatitidis may be important in chronic pulmonary infections.

Pharmacokinetics and Pharmacodynamics of Systemic Corticosteroids in Autoimmune and Inflammatory Diseases: A Review of Current Evidence.

Systemic corticosteroids have a long history of use in the treatment of autoimmune and inflammatory diseases. Both efficacy and safety show large interindividual variability (IIV), suggesting that corticosteroids may have the potential for individualised dosing strategies to optimise therapy. This systematic review aims to provide an overview of current evidence on the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of systemic corticosteroids in patients with autoimmune and inflammatory diseases. A systematic literature search was conducted in PubMed and Embase for PK/PD studies of systemic corticosteroids in autoimmune and inflammatory diseases in humans published until December 2023. Studies were scored from 1 to 5 according to criteria for the levels of evidence, as inspired by the Oxford Centre for Evidence-Based Medicine. Twelve studies (1981-2016) were included. The majority of these studies had a small sample size. The corticosteroids involved were prednisone, prednisolone, methylprednisolone and budesonide. Substantial IIV of corticosteroid PK was described in all studies. Evidence for a relationship between the PK of corticosteroids and efficacy was inconclusive and limited. However, there was some evidence for a relationship between the PK of prednisolone and the severity of Cushingoid features. There is insufficient evidence to draw firm conclusions on the potential associations between PK and clinical outcome of systemic corticosteroid treatment in autoimmune and inflammatory diseases. This is remarkable given the many decades that steroid drugs have been used in clinical care. Prospective research is recommended with robust and well-defined cohorts to fully quantify the PK/PD associations of corticosteroids.

High-efficiency bioconversion of phytosterol to bisnoralcohol by metabolically engineered Mycobacterium neoaurum in a micro-emulsion system.

21-Hydroxy-20-methylpregn-4-en-3-one (4-HBC, bisnoralcohol) is a crucial intermediate for the synthesis of steroidal drugs. Significant challenges including by-products formation and poor substrate solubility were still confronted in its main synthetic route by microbial conversion from phytosterol. Construction of a direct bioconversion pathway to 4-HBC and an efficient substrate emulsion system is therefore urgently required. In this study, three novel isoenzymes of 3-ketosteroid-Δ1-dehydrogenase (KstD) and 3-ketosteroid 9α-hydroxylase (KsH) in Mycobacterium neoaurum were excavated and identified as KstD4, KstD5, and KsHA3. A strain capable of fully directing the synthesis of 4-HBC was metabolically engineered via serial genetic deletion combined with enhanced expression of cholesterol oxidase (ChOx2) and enoyl-CoA hydratase (EchA19). Moreover, a micro-emulsion system combined with soybean oil and hydroxypropyl-β-cyclodextrin improved substrate solubility and bioavailability. In batch fermentation, molar yield of 96.7% with 39.5 gL-1 4-HBC was obtained from 50 gL-1 phytosterol. Our findings demonstrate the potential for industrial-scale biosynthesis of 4-HBC.

Identification of Risk Factors for Primary Osteoporosis: The Role of Cervical Ligament Ossification.

BACKGROUND Long-term clinical practice has suggested a possible association between ossification of cervical ligament (OCL) and primary osteoporosis (POP). However, there is a lack of relevant research data. This study aimed to clarify the potential relationship between OCL and POP, and propose new strategies for preventing the onset of POP. MATERIAL AND METHODS The study involved 107 patients. The patients' diagnosis included OCL (ossification of the posterior longitudinal ligament, ossification of the ligamentum flavum, and ossification of the nuchal ligament) and POP. Bone mineral density (BMD), types of OCL, types of ossification of posterior longitudinal ligament, age, sex, serum calcium, serum phosphorus, alkaline phosphatase, type I collagen amino-terminal extension peptide, type I collagen degradation products, osteocalcin N-terminal molecular fragments, 25-hydroxyvitamin D, and history of taking steroid drugs were collected. SPSS24.0 and GraphPad Prism 8 were used to obtain the risk factors for POP. RESULTS One-way analysis of variance found that OCL, ossification of posterior longitudinal ligament, alkaline phosphatase, and osteocalcin N-terminal molecular fragments had statistical significance on BMD of the femoral neck (P<0.05). The independent sample t test showed that patient sex had statistical significant effect on BMD (femoral neck) (P=0.036). Incorporating the above factors into multiple linear regression analysis, it was found that OCL, alkaline phosphatase, and osteocalcin N-terminal molecular fragments were risk factors affecting BMD of femoral neck (P<0.05). CONCLUSIONS OCL, osteocalcin N-terminal molecular fragments, and alkaline phosphatase are risk factors for POP.

Production of Steroid Hormones in Galena Opava

The drug product Antigest of the company Spofa was launched as soon as in 1965 and Czechoslovakia thus became forth country in the world where oral anticonception was introduced. The gestagen component of Antigest was methenmanidon acetate (superlutin), an original substance developed in the Research Institute of Natural Drugs. Superlutin and some other steroid drugs were produced in the Galena Opava plant. In the article, all the syntheses utilized in the manufacture of steroid drugs in Galena are described and the reasons why the manufacture of steroid drugs was terminated at the beginning of eighties are explained.

Association Between the Oxidative Balance Score and Endometriosis: A Population-Based Study.

To investigate the association between the oxidative balance score (OBS) and endometriosis. This cross-sectional study used four cycles of the National Health and Nutrition Examination Survey (NHANES) (1999-2000, 2001-2002, 2003-2004, and 2005-2006). OBS involved 16 dietary nutrients and 4 lifestyle factors, including 5 pro-oxidants and 15 anti-oxidants. According to weighted quartiles, the OBS was divided into four categories: < 12.54, 12.54-18.70, 18.71-24.68, and > 24.68. Endometriosis was diagnosed based on a question from the reproductive health questionnaire. Weighted multivariate logistic analysis was used to investigate the association between OBS and endometriosis. Subgroup analysis was performed based on menstrual regularity and female hormone use. A total of 5095 women were included, with 1140 (22.37%), 1232 (24.18%), 1224 (24.02%), and 1499 (29.42%) women in the OBS < 12.54, of 12.54-18.70, of 18.71-24.68, and > 24.68 categories, respectively. After adjusting age, race, family poverty-to-income ratio (PIR), education level, uterine fibroids, menstrual regularity, oophorectomy, female hormone use, hypertension, dyslipidemia, and steroid drug, a high OBS (> 24.68) was found to be associated with lower odds of endometriosis [odds ratio (OR) = 0.70, 95% confidence interval (CI): 0.50-0.97, P = 0.033] compared to a low OBS (< 12.54). The similar result was also found in women with irregular menstruation (OR = 0.58, 95% CI: 0.37-0.91, P = 0.020) and with female hormone use (OR = 0.71, 95% CI: 0.52-0.98, P = 0.037). A high OBS was associated with lower odds of endometriosis, especially in women with irregular menstruation and female hormone use.

Biotransformation of hydrocortisone succinate with whole cell cultures of Monascus purpureus and Cunninghamella echinulata

Hydrocortisone succinate (1) is a synthetic anti-inflammatory drug and key intermediate in the synthesis of other steroidal drugs. This work is based on the fungal biotransformation of 1, using Monascus purpureus and Cunninghamella echinulata strains. Comopound 1 was transformed into four metabolites, identified as hydrocortisone (2), 11β-hydroxyandrost-4-en-3,17-dione (3), Δ1-cortienic acid (4), and hydrocortisone-17-succinate (5), obtained through side chain cleavage, hydrolysis, dehydrogenation, and oxidation reactions. These compounds have previously been synthesized either chemically or enzymatically from different precursors. Though this is not the first report on the biotransformation of 1, but it obviously is a first, where the biotransformed products of compound 1 have been characterized structurally with the help of modern spectroscopic techniques. It is noteworthy that these products have already shown biological potential, however a more thorough investigation of the anti-inflammatory properties of these metabolites would be of high value. These results not only emphasize upon the immense potential of biotransformation in catalysis of reactions, otherwise not-achievable chemically, but also holds promise for the development of novel anti-inflammatory compounds.