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European Journal of Dentistry May 2024Osteoporosis is a disease characterized by disruption of the bone microarchitecture. It is observed in both sexes, but to a greater extent in women. It affects the whole...
Osteoporosis is a disease characterized by disruption of the bone microarchitecture. It is observed in both sexes, but to a greater extent in women. It affects the whole body, including the jaws. The main indicator of the presence of osteoporosis accepted by the World Health Organization is bone mineral density. The aim of this article is to find data on the influence of osteoporosis on apical periodontitis, to investigate how the intake of osteoporosis drugs affects apical periodontitis, and to establish various data that may be of benefit to the dental practitioner when treating patients with osteoporosis and apical periodontitis. Open-access publications are included. The presence of osteoporosis is important to the dentist. Apical periodontitis in these patients has a faster progression. They are characterized by inflammation and destruction of the tissues located around the tooth root. Osteoporosis has a destructive effect on bone tissue through different mechanisms: nuclear factor-κβ ligand and NLRP3/Caspase-1/IL-1β cascade. It is also associated with low estrogen levels. Various medications such as corticosteroids, bisphosphonates (alendronate, zoledronate (Zoledronic acid), calcitonin, raloxifene, and strontium used to treat osteoporosis can affect the course of apical periodontitis. When treating patients with periapical lesions, the dentist must take a proper medical history and general medical history. In cases of osteoporosis or taking bisphosphonates and other medications, consideration should be given to whether consultation with a specialist is necessary, what treatment approach would be most appropriate, and what the prognosis will be. Chronic diseases affect both the general state of the body and dental health. It has been found that in patients with osteoporosis, inflammation of the apical periodontium develops with faster bone resorption. Before starting dental treatment, it is important to specify the etiology of osteoporosis, the bone density of each patient, as well as the medications they are taking.
PubMed: 38759999
DOI: 10.1055/s-0044-1785533 -
International Journal of Molecular... Apr 2024Estrogen plays an important role in osteoporosis prevention. We herein report the possible novel signaling pathway of 17β-estradiol (E2) in the matrix mineralization of...
Estrogen plays an important role in osteoporosis prevention. We herein report the possible novel signaling pathway of 17β-estradiol (E2) in the matrix mineralization of MC3T3-E1, an osteoblast-like cell line. In the culture media-containing stripped serum, in which small lipophilic molecules such as steroid hormones including E2 were depleted, matrix mineralization was significantly reduced. However, the E2 treatment induced this. The E2 effects were suppressed by ICI182,780, the estrogen receptor (ER)α, and the ERβ antagonist, as well as their mRNA knockdown, whereas Raloxifene, an inhibitor of estrogen-induced transcription, and G15, a G-protein-coupled estrogen receptor (GPER) 1 inhibitor, had little or no effect. Furthermore, the E2-activated matrix mineralization was disrupted by PMA, a PKC activator, and SB202190, a p38 MAPK inhibitor, but not by wortmannin, a PI3K inhibitor. Matrix mineralization was also induced by the culture media from the E2-stimulated cell culture. This effect was hindered by PMA or heat treatment, but not by SB202190. These results indicate that E2 activates the p38 MAPK pathway via ERs independently from actions in the nucleus. Such activation may cause the secretion of certain signaling molecule(s), which inhibit the PKC pathway. Our study provides a novel pathway of E2 action that could be a therapeutic target to activate matrix mineralization under various diseases, including osteoporosis.
Topics: Animals; Mice; Estradiol; Osteoblasts; Signal Transduction; Calcification, Physiologic; Cell Line; p38 Mitogen-Activated Protein Kinases; Receptors, Estrogen; Estrogens; Estrogen Receptor alpha
PubMed: 38731947
DOI: 10.3390/ijms25094727 -
Pharmacological Research Jun 2024Neuropsychiatric disorders shorten human life spans through multiple ways and become major threats to human health. Exercise can regulate the estrogen signaling, which... (Review)
Review
Neuropsychiatric disorders shorten human life spans through multiple ways and become major threats to human health. Exercise can regulate the estrogen signaling, which may be involved in depression, Alzheimer's disease (AD) and Parkinson's disease (PD), and other neuropsychiatric disorders as well in their sex differences. In nervous system, estrogen is an important regulator of cell development, synaptic development, and brain connectivity. Therefore, this review aimed to investigate the potential of estrogen system in the exercise intervention of neuropsychiatric disorders to better understand the exercise in neuropsychiatric disorders and its sex specific. Exercise can exert a protective effect in neuropsychiatric disorders through regulating the expression of estrogen and estrogen receptors, which are involved in neuroprotection, neurodevelopment, and neuronal glucose homeostasis. These processes are mediated by the downstream factors of estrogen signaling, including N-myc downstream regulatory gene 2 (Ndrg2), serotonin (5-HT), delta like canonical Notch ligand 1 (DLL1), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), etc. In addition, exercise can act on the estrogen response element (ERE) fragment in the genes of estrogenic downstream factors like β-amyloid precursor protein cleavase 1 (BACE1). However, there are few studies on the relationship between exercise, the estrogen signaling pathway, and neuropsychiatric disorders. Hence, we review how the estrogen signaling mediates the mechanism of exercise intervention in neuropsychiatric disorders. We aim to provide a theoretical perspective for neuropsychiatric disorders affecting female health and provide theoretical support for the design of exercise prescriptions.
Topics: Humans; Estrogens; Animals; Mental Disorders; Exercise; Exercise Therapy; Signal Transduction; Receptors, Estrogen
PubMed: 38704108
DOI: 10.1016/j.phrs.2024.107201 -
Yakugaku Zasshi : Journal of the... 2024Transdermal drug delivery is a formulation in which the drug is absorbed through the skin for systemic action. Its advantages include avoidance of first-pass effects,... (Review)
Review
Transdermal drug delivery is a formulation in which the drug is absorbed through the skin for systemic action. Its advantages include avoidance of first-pass effects, sustained drug supply, and ease of administration and discontinuation. Drugs administered transdermally transfer into the blood circulation through the stratum corneum, epidermis, and dermis. The stratum corneum on the skin surface plays a barrier function in skin absorption. Therefore, developing of transdermal drug delivery systems requires innovations that overcome the barrier function of the stratum corneum and improve skin permeation. This review examines the usefulness of transdermal formulations based on solid nanoparticles using raloxifene. Milled raloxifene was gelled with (mRal-NPs) or without menthol (Ral-NPs) using Carbopol. The drug release and transdermal penetration were measured using a Franz diffusion cell, and the therapeutic evaluation of osteoporosis was determined in an ovariectomized rat model. Although the raloxifene released from Ral-NPs remained in the nanoparticle state, the skin penetration of raloxifene nanoparticles was prevented by the stratum corneum in rat. The inclusion of menthol in the formulation attenuated the barrier function of the stratum corneum and permitted raloxifene nanoparticles to penetrate through the skin. Moreover, macropinocytosis relates to the formulation's skin penetration, including menthol (mRal-NPs). Applying mRal-NPs attenuated the decreases in calcium level and stiffness of bones of ovariectomized rats. This information can support future studies aimed at designing novel transdermal formulations.
Topics: Animals; Administration, Cutaneous; Skin Absorption; Raloxifene Hydrochloride; Menthol; Nanoparticles; Drug Delivery Systems; Rats; Humans; Skin; Nanotechnology; Drug Liberation; Osteoporosis; Female; Drug Development
PubMed: 38692925
DOI: 10.1248/yakushi.23-00178-1 -
JCEM Case Reports May 2024We report a case of persistent gynecomastia in a healthy 20-year-old man after 1 month of low-dose finasteride. Finasteride was discontinued after 2 months, and... (Review)
Review
We report a case of persistent gynecomastia in a healthy 20-year-old man after 1 month of low-dose finasteride. Finasteride was discontinued after 2 months, and gynecomastia was unchanged 5 months after drug withdrawal. The gynecomastia regressed but did not resolve after 6 months of treatment with raloxifene, a selective estrogen receptor modulator. One year later, bilateral mammoplasty was performed to remove the remaining breast tissue. Finasteride, a 5-alpha-reductase inhibitor, is widely used for the treatment of androgenetic alopecia. Gynecomastia is an expected side effect of this therapy given its mechanism of action. However, only 8 cases of gynecomastia have been reported with low-dose (1 mg daily) finasteride treatment since its approval for androgenetic alopecia in 1997. This raises the concern that gynecomastia resulting from low-dose finasteride is significantly underreported, causing inadequately informed patients. Further, because of the risk of gynecomastia, it is important for prescribing physicians to counsel patients regarding this complication and to consider early intervention when finasteride-induced gynecomastia first arises to prevent fibrosis and thus irreversible gynecomastia.
PubMed: 38660487
DOI: 10.1210/jcemcr/luae050 -
BioRxiv : the Preprint Server For... Apr 2024Currently, there are no specific antiviral therapeutic approaches targeting Human papillomaviruses (HPVs), which cause around 5% of all human cancers. Specific antiviral...
Currently, there are no specific antiviral therapeutic approaches targeting Human papillomaviruses (HPVs), which cause around 5% of all human cancers. Specific antiviral reagents are particularly needed for HPV-related oropharyngeal cancers (HPVOPCs) whose incidence is increasing and for which there are no early diagnostic tools available. We and others have demonstrated that the estrogen receptor alpha (ERα) is overexpressed in HPVOPCs, compared to HPV-negative cancers in this region, and that these elevated levels are associated with an improved disease outcome. Utilizing this HPV specific overexpression profile, we previously demonstrated that estrogen attenuates the growth and cell viability of HPV keratinocytes and HPV cancer cells . Expansion of this work failed to replicate this sensitization. The role of stromal support from the tumor microenvironment (TME) has previously been tied to both the HPV lifecycle and therapeutic responses. Our investigations revealed that co-culture with fibroblasts attenuated HPV specific estrogen growth responses. Continuing to monopolize on the HPV specific overexpression of ERα, our co-culture models then assessed the suitability of the selective estrogen receptor modulators (SERMs), raloxifene and tamoxifen, and showed growth attenuation in a variety of our models to one or both of these drugs Utilization of these SERMs closely resembled the sensitization predicted by our co-culture models. Therefore, the fibroblast co-culture model better predicts responses. We propose that utilization of our co-culture model can accelerate cancer therapeutic drug discovery.
PubMed: 38644998
DOI: 10.1101/2024.04.09.588680 -
Schizophrenia Research May 2024Maternal immune activation (MIA) during pregnancy is known to increase the risk of development of schizophrenia in the offspring. Sex steroid hormone analogues have been...
Maternal immune activation (MIA) during pregnancy is known to increase the risk of development of schizophrenia in the offspring. Sex steroid hormone analogues have been proposed as potential antipsychotic treatments but the mechanisms of action involved remain unclear. Estrogen has been shown to alter N-methyl-d-aspartate (NMDA) receptor binding in the brain. We therefore studied the effect of chronic treatment with 17β-estradiol, its isomer, 17α-estradiol, and the selective estrogen receptor modulator, raloxifene, on MIA-induced psychosis-like behaviour and the effect of the NMDA receptor antagonist, MK-801. Pregnant rats were treated with saline or the viral mimetic, poly(I:C), on gestational day 15. Adult female offspring were tested for changes in baseline prepulse inhibition (PPI) and the effects of acute treatment with MK-801 on PPI and locomotor activity. Poly(I:C) offspring had significantly lower baseline PPI compared to control offspring, and this effect was prevented by 17β-estradiol and raloxifene, but not 17α-estradiol. MK-801 reduced PPI in control offspring but had no effect in poly(I:C) offspring treated with vehicle. Chronic treatment with 17β-estradiol and raloxifene restored the effect of MK-801 on PPI. There were no effects of MIA or estrogenic treatment on MK-801 induced locomotor hyperactivity. These results show that MIA affects baseline PPI as well as NMDA receptor-mediated regulation of PPI in female rats, and strengthen the view that estrogenic treatment may have antipsychotic effects.
Topics: Animals; Female; Estradiol; Raloxifene Hydrochloride; Schizophrenia; Pregnancy; Prepulse Inhibition; Disease Models, Animal; Dizocilpine Maleate; Poly I-C; Receptors, N-Methyl-D-Aspartate; Prenatal Exposure Delayed Effects; Rats; Excitatory Amino Acid Antagonists; Male; Selective Estrogen Receptor Modulators; Estrogens; Motor Activity
PubMed: 38642484
DOI: 10.1016/j.schres.2024.04.008 -
Revista Brasileira de Ortopedia Apr 2024To evaluate the effects of estrogen, raloxifene and genistein on the expression of (kisspeptin), (kisspeptin receptor), (androgen receptor) and (insulin...
To evaluate the effects of estrogen, raloxifene and genistein on the expression of (kisspeptin), (kisspeptin receptor), (androgen receptor) and (insulin receptor) in the bones of ovariectomized rats. Forty-eight adult rats were randomly divided into 6 groups, containing 8 animals each: G1-nonovariectomized control; G2-ovariectomized and treated with conjugated equine estrogens (50 µg/Kg/day); G3-ovariectomized and treated with raloxifene (0.75 mg/kg/day); G4-ovariectomized animal that received soy extract with genistein (300 mg/kg/day); G5-ovariectomized animal that received estrogen and genistein; and G6-ovariectomized animal that received estrogen and raloxifene. Three months after surgery, the castrated animals received the drugs orally daily for 120 days. All animals were sacrificed after this period, by deepening the anesthesia. The left tibia was removed for total RNA extraction and analysis of gene expression of , , and , by quantitative real-time polymerase chain reaction (qRT-PCR). was not detected in any of the treated groups. , and showed higher expression in the G3 group ( < 0.001), while lower levels of transcripts for these genes were observed in G4 and G5. G2 animals showed hypoexpression of the evaluated genes. The results indicate that raloxifene, alone or combined with estrogen, was able to induce the expression of genes associated with the recovery of bone tissue homeostasis in ovariectomized rats.
PubMed: 38606141
DOI: 10.1055/s-0044-1779319 -
Heliyon Mar 2024Leishmaniasis is one of the top 10 neglected tropical diseases. Globally, it impacts more than 12 million individuals. In light of the absence of a safer, affordable...
Leishmaniasis is one of the top 10 neglected tropical diseases. Globally, it impacts more than 12 million individuals. In light of the absence of a safer, affordable treatment for the Leishmaniasis, along with therapeutic failures and drug resistance, novel therapeutic strategies are necessary to discover new drugs. Treatment would benefit by concentrating on the precise targets that are crucial for the parasite to survive. A target that aids in the organism's survival under oxidative stress is trypanothione synthetase (TyS), which is a component of the trypanothione pathway in spp. To find potential TyS inhibitors for the purpose of discovering novel antileishmanial drugs, we used a virtual screening strategy. Using the Glide module of Schrodinger-suite 2023, an FDA-approved library containing 2000 drugs from the ZINC-15 database was screened against the TyS. Dostinex, raloxifene, and formoterol showed good docking scores of -10.568 kcal/mol, -10.446 kcal/mol, and -56.21 kcal/mol, as well as good binding energies of -70.41 kcal/mol, -56.21 kcal/mol, and -64.15 kcal/mol respectively. The stability of the ligand-protein complexes was assessed further with the help of Desmond to execute a 100-ns molecular dynamics simulation. The Prime module was utilised to perform post-MM/GBSA analysis on these three molecules along with the toxicity profiling using Protox II web server. This study suggests that dostinex, formoterol, and raloxifene may act as effective inhibitors of the TyS receptor which could be used as novel antileishmanial agents for the therapeutic applications. Thorough preclinical studies are necessary to confirm the identified compounds chemotherapeutic qualities.
PubMed: 38509977
DOI: 10.1016/j.heliyon.2024.e27602 -
Brain, Behavior, and Immunity May 2024Dopamine dysregulation contributes to psychosis and cognitive deficits in schizophrenia that can be modelled in rodents by inducing maternal immune activation (MIA). The...
Dopamine dysregulation contributes to psychosis and cognitive deficits in schizophrenia that can be modelled in rodents by inducing maternal immune activation (MIA). The selective estrogen receptor (ER) modulator, raloxifene, can improve psychosis and cognition in men and women with schizophrenia. However, few studies have examined how raloxifene may exert its therapeutic effects in mammalian brain in both sexes during young adulthood (age relevant to most prevalent age at diagnosis). Here, we tested the extent to which raloxifene alters dopamine-related behaviours and brain transcripts in young adult rats, both control and MIA-exposed females and males. We found that raloxifene increased amphetamine (AMPH)-induced locomotor activity in female controls, and in contrast, raloxifene reduced AMPH-induced locomotor activity in male MIA offspring. We did not detect overt prepulse inhibition (PPI) deficits in female or male MIA offspring, yet raloxifene enhanced PPI in male MIA offspring. Whereas, raloxifene ameliorated increased startle responsivity in female MIA offspring. In the substantia nigra (SN), we found reduced Drd2s mRNA in raloxifene-treated female offspring with or without MIA, and increased Comt mRNA in placebo-treated male MIA offspring relative to placebo-treated controls. These data demonstrate an underlying dopamine dysregulation in MIA animals that can become more apparent with raloxifene treatment, and may involve selective alterations in dopamine receptor levels and dopamine breakdown processes in the SN. Our findings support sex-specific, differential behavioural responses to ER modulation in MIA compared to control offspring, with beneficial effects of raloxifene treatment on dopamine-related behaviours relevant to schizophrenia found in male MIA offspring only.
Topics: Humans; Young Adult; Rats; Female; Male; Animals; Adult; Raloxifene Hydrochloride; Dopamine; Receptors, Estrogen; Selective Estrogen Receptor Modulators; Amphetamine; RNA, Messenger; Prenatal Exposure Delayed Effects; Behavior, Animal; Poly I-C; Disease Models, Animal; Mammals
PubMed: 38431238
DOI: 10.1016/j.bbi.2024.02.034