Article
Cell Biology
Johnson M. Moliki, Tawanda J. Nhundu, Leo Maritz, Chanel Avenant, Janet P. Hapgood
Summary: The pro-inflammatory cytokine CCL20 can be regulated by glucocorticoids and progestins, as well as other pro-inflammatory mediators, and this regulation can impact immune function and disease outcomes.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2023)
Article
Immunology
Alexis J. Bick, Chanel Avenant, Michele Tomasicchio, Zephne van der Spuy, Janet P. Hapgood
Summary: Both luteal phase progesterone levels and the use of the progestin-only contraceptive depo-medroxyprogesterone acetate (DMPA-IM) have been linked to increased S/HIV acquisition. The mechanisms underlying these associations are not well understood. This study found that DMPA-IM increases HIV-1 infection in a different manner than luteal phase hormones, involving the glucocorticoid receptor and changes in CCR5 and CD69 expression.
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2022)
Article
Chemistry, Analytical
Claire E. Knezevic, Teresa L. Parsons, Ryann Gollings, Aashish Pandey, Mark A. Marzinke
Summary: A multiplexed LC-MS/MS assay for the quantification of ETO, LNG, MPA, and NET has been developed and validated. The assay showed acceptable precision and accuracy for all progestins and may be used to evaluate progestin pharmacology in downstream studies.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Obstetrics & Gynecology
Richard H. Cockrum, Jackie Soo, Sandra A. Ham, Kenneth S. Cohen, Shari G. Snow
Summary: This study evaluated the association between seven progestogens and incident acute venous thromboembolism (VTE) among women of reproductive age. Higher-dose progestogens, specifically norethindrone acetate and medroxyprogesterone acetate, were found to be significantly associated with increased odds of VTE. Further research on progestogen type, dose, and indication for use is warranted.
OBSTETRICS AND GYNECOLOGY
(2022)
Article
Obstetrics & Gynecology
Dawn Palaszewski, Margaret Abraham
Summary: Adolescents experiencing severe uterine bleeding typically only require medical management, with surgical intervention being rarely necessary; the decision to use estrogen should be personalized based on risk-benefit assessment.
OBSTETRICS AND GYNECOLOGY
(2021)
Article
Plant Sciences
Kailiang Li, Djeneba Diakite, Julia Austin, Jung-Ho Lee, Daniel D. Lantvit, Brian T. Murphy, Joanna E. Burdette
Summary: Baicalein functions as a PR antagonist in vivo and attenuates the antiproliferative effect of P4 on luminal epithelium, while not changing levels of PR or GR RNA or protein in the uterus. RNA sequencing data suggest that transcripts significantly altered by baicalein are regulated in the opposite direction by P4, indicating potential opposing effects of baicalein and P4 in the uterus.
JOURNAL OF NATURAL PRODUCTS
(2022)
Review
Obstetrics & Gynecology
Sara Clemenza, Tommaso Capezzuoli, Ecem Eren, Jose M. Garcia Garcia, Silvia Vannuccini, Felice Petraglia
Summary: Estrogen dependence and progesterone resistance are essential in the development of endometriosis, making hormonal therapies the most effective treatment. Progestins, as synthetic compounds, mimic the effects of progesterone and are the first-line approach for long-term management. They suppress ovarian steroidogenesis, decrease inflammation, induce apoptosis in endometriotic cells, and inhibit angiogenesis, ultimately relieving pain and improving the quality of life. Available progestin options include Di-enogest, Medroxyprogesterone acetate, and Norethisterone acetate, but other progestins such as Dyhidrogesterone, Levonorgestrel, and Desogestrel have also shown efficacy in treating endometriosis-associated pain. This review aims to summarize the evidence on the use of progestins for endometriosis treatment.
MINERVA OBSTETRICS AND GYNECOLOGY
(2023)
Article
Immunology
Jenell S. Coleman, Clarissa P. Diniz, Edward J. Fuchs, Mark A. Marzinke, Wutyi Aung, Rahul P. Bakshi, Homayoon Farzadegan, Jay H. Bream, Tricia L. Nilles, Sherry Hudson, Namandje N. Bumpus, George J. Schwartz, Michael A. Rosenblum, James F. Rooney, Craig W. Hendrix
Summary: Depot medroxyprogesterone acetate (DMPA) does not affect the pharmacokinetics or renal function of emtricitabine and tenofovir disoproxil fumarate (F/TDF). F/TDF reduces HIV infection while DMPA alone does not increase HIV infection.
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
(2023)
Article
Oncology
Xiangyan Ruan, Alfred O. O. Mueck
Summary: This study systematically investigates the role of PGRMC1 in breast cancer. In vitro and animal experiments demonstrate that PGRMC1 plays a critical role in synthetic progestogen-induced breast cancer proliferation. Clinical studies show that the expression of PGRMC1 in breast cancer tissue is associated with tumor characteristics and patient survival. Therefore, PGRMC1 may serve as a predictive marker for the prognosis of breast cancer patients and the risk of breast cancer during hormone replacement therapy.
Article
Public, Environmental & Occupational Health
Lisa M. Noguchi, Jeanne M. Marrazzo, Barbara Richardson, Sharon L. Hillier, Jennifer E. Balkus, Thesla Palanee-Phillips, Gonasagrie Nair, Ravindre Panchia, Jeanna Piper, Kailazarid Gomez, Gita Ramjee, Z. Mike Chirenje
Summary: Among South African participants in the VOICE trial, there were differences in baseline HSV-2 prevalence between DMPA-IM and NET-EN users, but no significant differences in the incidence of chlamydia, gonorrhea, trichomoniasis, syphilis, or HSV-2 infection were found.
FRONTIERS IN REPRODUCTIVE HEALTH
(2021)
Article
Chemistry, Medicinal
T. A. Fedotcheva, N. Sheina, V. A. Parshin, A. Semeikin, V. A. Votyakov, N. L. Shimanovsky
Summary: Gestobutanoyl, a pregnane steroid, demonstrates glucocorticoid, mineralocorticoid, and antiandrogenic effects in rats, but lacks estrogenic activity.
PHARMACEUTICAL CHEMISTRY JOURNAL
(2021)
Article
Critical Care Medicine
Aliasgar Esmail, Suzette Oelofse, Carl Lombard, Rubeshan Perumal, Linda Mbuthini, Akhter Goolam Mahomed, Ebrahim Variava, John Black, Patrick Oluboyo, Nelile Gwentshu, Eric Ngam, Tertius Ackerman, Linde Marais, Lynelle Mottay, Stuart Meier, Anil Pooran, Michele Tomasicchio, Julian Te Riele, Brigitta Derendinger, Norbert Ndjeka, Gary Maartens, Robin Warren, Neil Martinson, Keertan Dheda
Summary: The study explored the effectiveness of a new all-oral regimen compared to a standard injectable-based regimen for the treatment of drug-resistant tuberculosis. The all-oral regimen showed significantly improved treatment outcomes but had a higher incidence of drug toxicity. These findings provide important insights for the development of future treatment regimens for drug-resistant tuberculosis.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Editorial Material
Chemistry, Multidisciplinary
John G. Woodland, Kelly Chibale
Summary: This article traces the history of quinine from being a medicine used for colonialism to its roles as a chemical target, fluorescence standard, and key ingredient in popular drinks.
Article
Materials Science, Biomaterials
Mona T. Elsemary, Michelle F. Maritz, Louise E. Smith, Majid Warkiani, Veronika Bandara, Silvana Napoli, Simon C. Barry, Justin T. Coombs, Benjamin Thierry
Summary: CAR-T cell therapy manufacturing process is complex and costly with potential defects. Inertial microfluidics can effectively increase cell viability, reduce cryoprotectant usage, and maintain CAR-T cell functionality.
Article
Pharmacology & Pharmacy
Pouya Dehghankelishadi, Michelle F. Maritz, Parisa Badiee, Benjamin Thierry
Summary: This study demonstrates the potential of using high-density lipoprotein nanoparticles as a delivery system for radio-sensitising RNA in head and neck cancer cells. The results show enhanced radiation effects and increased apoptosis when miR34a is delivered by HDL nanoparticles.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
Parisa Badiee, Michelle F. Maritz, Benjamin Thierry
Summary: A nanoformulation of a small molecule GSK3 inhibitor has been developed as a potential alternative to antibody-based checkpoint inhibition. The nanoformulation efficiently inhibits PD-1 expression and improves the survival and proliferation of CAR-T cells, while also increasing the population of memory T cells.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Chemistry, Multidisciplinary
Pouya Dehghankelishadi, Michelle F. Maritz, Nicole Dmochowska, Parisa Badiee, Edward Cheah, Ivan Kempson, Ross Berbeco, Benjamin Thierry
Summary: This study developed a nanoparticle formulation of simvastatin, which enhanced the radiobiological response in head and neck squamous cell carcinoma models. The formulation achieved this by improving cellular uptake and utilizing the biological activity of high density lipoprotein nanoparticles. The radiosensitizing potency of the formulation was also validated in a mouse model.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Biochemistry & Molecular Biology
Maleshigo Komane, Chanel Avenant, Renate Louw-du Toit, Donita J. Africander, Janet P. Hapgood
Summary: This study compared the GR activities of several progestins and found that MPA, ETG, and NES have stronger binding affinities to GR and exhibit transactivation and transrepression activities, while LNG and NET show little to no activity in transactivation models but have some transrepressive activity.
Editorial Material
Biochemistry & Molecular Biology
Susan Winks, John G. Woodland, Goonaseelan 'Colin' Pillai, Kelly Chibale
Summary: The H3D Centre, a research unit based in South Africa, has achieved numerous successes and could potentially serve as a valuable model for drug discovery and development in Africa.
Review
Biochemistry & Molecular Biology
Alexis J. Bick, Salndave B. Skosana, Chanel Avenant, Janet P. Hapgood
Summary: Quantification of serum progestin levels in clinical contraceptive studies is crucial for understanding progestin pharmacokinetics and improving the accuracy of self-reported contraceptive use. Current methods vary widely and lack standardization, leading to potential overestimation of progestin levels. Inter-individual and inter-study variation in maximum progestin concentrations post-injection highlights the need for standardized quantification methods and sampling time.
Article
Immunology
Alexis J. Bick, Chanel Avenant, Michele Tomasicchio, Zephne van der Spuy, Janet P. Hapgood
Summary: Both luteal phase progesterone levels and the use of the progestin-only contraceptive depo-medroxyprogesterone acetate (DMPA-IM) have been linked to increased S/HIV acquisition. The mechanisms underlying these associations are not well understood. This study found that DMPA-IM increases HIV-1 infection in a different manner than luteal phase hormones, involving the glucocorticoid receptor and changes in CCR5 and CD69 expression.
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2022)
Article
Cell Biology
Johnson M. Moliki, Tawanda J. Nhundu, Leo Maritz, Chanel Avenant, Janet P. Hapgood
Summary: The pro-inflammatory cytokine CCL20 can be regulated by glucocorticoids and progestins, as well as other pro-inflammatory mediators, and this regulation can impact immune function and disease outcomes.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Aliasgar Esmail, Philippa Randall, Suzette Oelofse, Michele Tomasicchio, Anil Pooran, Richard Meldau, Edson Makambwa, Lynelle Mottay, Shameem Jaumdally, Gregory Calligaro, Stuart Meier, Marianna de Kock, Tawanda Gumbo, Robin Mark Warren, Keertan Dheda
Summary: Two in every five patients with active tuberculosis (TB) remain undiagnosed or unreported, highlighting the need for urgent implementation of community-based active case-finding strategies. Through an open-label, randomized controlled trial in periurban informal settlements of Cape Town, South Africa, it was found that portable, battery-operated molecular diagnostic tools can shorten time-to-treatment initiation compared to conventional POC smear microscopy, potentially curtailing transmission.
Editorial Material
Chemistry, Medicinal
John G. Woodland, Gregory S. Basarab, Koketso Mogwera, Susan Winks, Kelly Chibale
ACS INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Gemma Turon, Jason Hlozek, John G. Woodland, Ankur Kumar, Kelly Chibale, Miquel Duran-Frigola
Summary: Streamlined data-driven drug discovery remains challenging, especially in resource-limited settings. Here, the authors present ZairaChem, an AI/ML tool that streamlines QSAR/QSPR modelling, implemented for the first time at the H3D Centre in South Africa.
NATURE COMMUNICATIONS
(2023)