Search

The production of androst-4-ene-3,17-dione (AD) by the steroidal microbial cell factory requires transcription factors (TFs) to participate in metabolic regulation. However, microbial cell factory lacks effective TFs that can respond to AD in its metabolic pathway. Additionally, finding and obtaining natural TFs that specifically respond to AD is a complex and onerous task. In this study, we devised an artificial TF that responds to AD, termed AdT, based on structure-guided molecular dynamics (MD) simulation. According to MD analysis of the conformational changes of AdT after binding to AD, an LBD in which the N- and C-termini exhibited convergence tendencies was used as a microswitch to guide the assembly of a DNA-binding domain lexA, a linker (GGGGS)2, and a transcription activation domain B42 into an artificial TF. As a proof of design, a AD biosensor was designed and constructed in yeast on the basis of the ligand-binding domain (LBD) of hormone receptor. In addition, the transcription factor activity of AdT was increased by 1.44-fold for its variant F320Y. Overall, we created non natural TF elements for AD microbial cell factory, and expected that the design TF strategy will be applied to running in parallel to the signaling machinery of the host cell. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the chloroform extract of the roots of Cynanchum otophyllum (Asclepiadaceae) led to the isolation of a new cardiac aglycone, characterised as Cynanchin A (1), as well as one known cardenolide (2) and nine known C21 steroidal glycosides (3-10), Their structures were established by 1D and 2D NMR spectra referring to the literature, together with high-resolution mass spectrometric analysis. In the present research, the cytotoxic activities of the 11 compounds on five different human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480) were evaluated in vitro . Most of the tested compounds showed potent inhibitory activities towards the five cell lines.

The production of androst-4-ene-3,17-dione (AD) by the steroidal microbial cell factory requires transcription factors (TFs) to participate in metabolic regulation. However, microbial cell factory lacks effective TFs that can respond to AD in its metabolic pathway. Additionally, finding and obtaining natural TFs that specifically respond to AD is a complex and onerous task. In this study, we devised an artificial TF that responds to AD, termed AdT, based on structure-guided molecular dynamics (MD) simulation. According to MD analysis of the conformational changes of AdT after binding to AD, an LBD in which the N - and C -termini exhibited convergence tendencies was used as a microswitch to guide the assembly of a DNA-binding domain lexA, a linker (GGGGS) 2 , and a transcription activation domain B42 into an artificial TF. As a proof of design, a AD biosensor was designed and constructed in yeast on the basis of the ligand-binding domain (LBD) of hormone receptor. In addition, the transcription factor activity of AdT was increased by 1.44-fold for its variant F320Y. Overall, we created non-natural TF elements for AD microbial cell factory, and expected that the design TF strategy will be applied to running in parallel to the signaling machinery of the host cell., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: The connection between corticotherapy and neuropsychiatric symptoms is widely known, being one of the first questions we need to assess when presenting with first episode psychiatric symptoms or confusional state. Aims: To date, data on cases related to inhaled corticotherapy and neuropsychiatric effects is scarce. In this paper we describe a rare case in a young woman. Methods: The clinical case presented led us to try to understand the data published on the subject in order to discuss it in greater length. Results and Conclusions: We present and discuss a 27-year-old patient’s case, with no previous psychiatric disease, who was admitted to our Psychiatric ward after the onset of severe acute behavioural disturbance characterized by aggressiveness, visual and auditory hallucinatory activity, misidentification and altered conscience status. It was later found that seven days earlier she had been prescribed inhaled corticotherapy for a minor respiratory infection. A few days after corticotherapy withdrawal, the clinical symptoms improved significantly.

Uscharin‐like non‐classical cardenolides are considered to be useful as HIF‐1 inhibitors in the treatment of cancers. To develop more potent HIF‐1 inhibitors, oximes and oxime ethers of uscharin were designed and synthesized. Oximation of uscharin exhibited unexpectedly a regioselectivity and stereoselectivity at 3′‐thiazoline but not at the 19‐aldehyde group, since either E‐ketoxime derivative 2 or its ether 5 at C‐3′ was found as the only product during oximation of uscharin using hydroxylamine or methoxyamine at room temperature. Two 19‐aldoxime derivatives 4 and 6 were also synthesized. Ketoxime analogue 2 showed more potent inhibitory effect on HIF‐1 transcriptional activity than the parental uscharin. Ketoxime ether 5 and 19‐aldoxime 6 exhibited stronger HIF‐1 suppressing effect than digoxin (the positive control drug). Moreover, ketoxime derivative 2 displayed the most potent anti‐proliferative activity against MCF‐7 cancer cells among all compounds. An analysis of structure‐activity relationship revealed that 3′‐ketoxime is a superior moiety to a thiazoline ring, while 19‐aldoxime is inferior to an aldehyde counterpart. Our findings may provide some guidance for the rational design of uscharin‐based promising HIF‐1 inhibitors. [ABSTRACT FROM AUTHOR]

Chemical investigation of the soft coral Lobophytum lobophytum collected from the Red Sea led to the isolation of a new compound gorgostan-5,25-dien-3β-ol (1), and two known compounds gorgosterol (2), and alismol (3). Structures were elucidated by employing extensive NMR and HR-ESI-MS experiments. [ABSTRACT FROM AUTHOR]

Background Chronic low back pain (CLBP) is one of the most common complaints affecting the population worldwide including in Lebanon. Until 15 years ago, surgery was the treatment of choice. However, conservative measures are now preferred because of the large number of post-surgical complications, in addition to the many conditions where surgery cannot be performed. Objective The aim of our study is to determine the effectiveness of transformational epidural injection of ozone (TFEOI) in the management of CLBP among the Lebanese population in the Nabatieh area in comparison with patients who received transformational epidural steroid injection (TFESI). Methods A one-year (2016-2017) retrospective study where 100 patients with CLBP were selected from two hospitals (Alnajdah, and Ragheb Harb hospitals) and divided into two groups. Fifty patients were treated with Ozone injections while the other 50 were treated with steroid injections. For each patient, we recorded the type of pain, irradiation, paresthesia, and the type of injection given (steroid or Ozone). We used the patients' files and contacted them via phone calls. The results of this study were reached based on Vas Score and Mac Nab criteria which are subjective questionnaires. Results The study showed that the TFESI was effective for a short duration (86% of results were excellent and good after one month of injection, but they decreased to 16% after six months). On the other hand, TFEOI was effective over both short and long duration (82% excellent and good after one month, 64% excellent and good after six months). Conclusion Results from this study provide that ozone injection has high benefits in the management of CLBP in the Lebanese population., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Chemeisani et al.)

Orbital apex syndrome (OAS) is a rare disease that presents with a complex of symptoms, including ophthalmoplegia, ptosis and visual loss. Due to the poor prognosis, making a prompt diagnosis and administering the appropriate treatment must be initiated without delay if OAS is suspected. We report here on a case of a patient with sphenoid fungal balls, and he presented with acute visual loss and ophthalmoplegia.

Abstract: This study was aimed to improve knowledge about swine ovarian follicular function, paying attention to angiogenesis, since new vessel growth is a fundamental event in ovarian function. In particular, we investigated a potential involvement of netrin-1, a protein known as a guidance axon factor. Firstly, we studied the expression and immunolocalization of netrin-1 in swine ovarian follicle and its effect on cultured swine granulosa cell viability and steroidogenesis. Furthermore, aortic endothelial cells were employed to verify a possible netrin-1 effect on angiogenesis. Our data demonstrate the expression and the presence of netrin-1 in swine follicular fluid; in addition, it was shown that netrin-1 inhibits granulosa cell viability and estradiol 17β levels while it stimulates progesterone production. Netrin-1 also inhibits aortic endothelial cell growth in the angiogenesis bioassay. This effect appears to be mediated by inhibiting vascular endothelial growth factor and stimulating nitric oxide. Therefore, we hypothesize that netrin-1 could be important for follicular function in the swine. [ABSTRACT FROM AUTHOR]

Abstract: The applicability of comprehensive two-dimensional gas chromatography (GC×GC) for sterol analysis was investigated by separation and identification of endogenous sterols in standards, and spiked in human urine. The modulation temperature was optimized to achieve the best separation and signal enhancement. The separation pattern of trimethylsilyl (TMS) derivatives of sterols was compared on two complementary column sets. Whilst the BPX5/BPX50 column set offers better overall separation, BPX50/BPX5 provides better peak shape and sensitivity. Comparison of the identification power of GC×GC–TOFMS against both the NIST05 MS library and a laboratory created (in-house) TOFMS library was carried out on a free sterols extract of urine, derivatised and spiked at the World Anti-Doping Agency (WADA) limit of 2ngmL−1. The average match quality for 19 analysed sterols on the BPX50/BPX5 column set was 950/1000 when searched against the in-house library; only four were identified against the NIST05 library, at a match threshold of 800. The match quality of GC×GC–TOFMS spectra was superior to that for analysis using 1D GC–TOFMS for sterols spiked in urine at 10ngmL−1. An r 2 >0.997 was obtained for the concentration range between 0.25ngmL−1 and 10ngmL−1 for three selected sterols. The lowest limit of detection (LOD) was obtained for estrone (0.1ngmL−1) and the highest LOD was for 5α-androstan-3α,11β-diol-17-one, epitestosterone and cholesteryl butyrate (1ngmL−1), using a match threshold of at least 800 and signal-to-noise ratio of at least 10. TOFMS coupled to GC×GC enabled satisfactory identification of sterols in urine at their LOD. A minimum acceptable match (MAM) criterion for urinary sterols using 2D retention times and TOF mass spectra is introduced. This study shows that GC×GC–TOFMS yields high specificity for steroids derived from urine, with detection limits appropriate for use in doping control. [Copyright &y& Elsevier]

Immune compromise can modify the severity and manifestation of some parasitic infections. More widespread use of newer immnosuppressive therapies, the growing population of individuals with immunocompromised states as well as the prolonged survival of these patients have altered the pattern of parasitic infection. This review article discusses the burden and immunology of parasitic infections in patients who are immunocompromised secondary to congenital immunodeficiency, malnutrition, malignancy, and immunosuppressive medications. This review does not address the literature on parasitic infections in the setting of HIV-1 infection. [ABSTRACT FROM AUTHOR]

Liquid chromatography coupled to tandem mass spectrometry has been used for the detection and the structural characterization of T-rich model oligonucleotides covalently modified by estradiol-2,3-quinone. After separation by gradient elution, adducts were analyzed by negative electrospray mass spectrometry, enabling to evidence and localize the modifications in the oligonucleotide sequence. Modifications by one molecule of estrogen were evidenced on purines (A, G) whereas no reaction was observed on pyrimidic bases (T). Isomeric adducts were differentiated using tandem mass spectrometry, and energy resolved mass spectrometry allowed to underline differences in the behavior of the adducts towards collisional excitation into an ion trap device. [Copyright &y& Elsevier]

Leptin is a hormone secreted mainly by the adipose cells with a primary role in the regulation of body weight by establishing a feedback loop between the energy reserves and the hypothalamic centers that control food intake. Recent data suggest that, in addition, leptin interacts with other endocrine systems to provide critical information about the size of the fat stores, acting as a permissive factor that allows the triggering of energy-demanding situations, as the onset of puberty and the reproduction, only when the size of the fuel reserve is large enough to guarantee its success. In addition, leptin appears to play a role during pregnancy and lactation, as it is produced by the placenta and is present in maternal milk. The fact that leptin levels are always higher in females, even after correcting for body fat content, suggests that the interaction between the adipose tissue and the reproductive system is modulated in a different way in males and females by androgenic and estrogenic hormones. In fact, adipose tissue samples taken from male donors are completely refractory in vitro to the action of both estrogens and androgens. On the contrary, dihydrotestosterone, androstenedione and dehydroepiandrosterone-S are potent inhibitors of leptin secretion, while estradiol induces a strong stimulation in adipose tissue taken from women. Testosterone is devoid of activity in either gender. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 19-month-old toddler with perinatally acquired hepatitis C infection. The child is positive with hepatitis C virus (HCV) RNA and HCV antibody and got her infection from her mother who had a history of intravenous drug use. The article discusses the use of steroids as a treatment for type 2 autoimmune hepatitis which may exacerbate the HCV infection.

Seven undescribed C21 steroids, namely cynanchin A – G , together with thirteen known analogues, were isolated from the roots of cynanchum otophyllum. Their structures were elucidated by 1D, 2D NMR and MS spectra, as well as chemical methods. Meanwhile, all of isolates were tested for their anti-hepatic fibrosis activity. Among them, compounds 4–6 , 10–12 and 14–17 showed moderate or significant inhibitory effects for the proliferation of hepatic stellate cells (HSCs) induced by transforming growth factor- β 1 (TGF- β 1) in vitro. Seven undescribed steriods together with thirteen known compounds were isolated from the roots of Cynanchum otophyllum. Some of them showed moderate or marked anti-hepatic fibrosis activity. Unlabelled Image [ABSTRACT FROM AUTHOR]

Orbital apex syndrome (OAS) is a rare disease that presents with a complex of symptoms, including ophthalmoplegia, ptosis and visual loss. Due to the poor prognosis, making a prompt diagnosis and administering the appropriate treatment must be initiated without delay if OAS is suspected. We report here on a case of a patient with sphenoid fungal balls, and he presented with acute visual loss and ophthalmoplegia.