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Journal of Biophotonics May 2024Photobiomodulation (PBM) has attracted widespread attention in suppressing various pain and inflammation. Primary dysmenorrhea (PD) primarily occurs in adolescents and...
Photobiomodulation (PBM) has attracted widespread attention in suppressing various pain and inflammation. Primary dysmenorrhea (PD) primarily occurs in adolescents and adult females, and the limited effectiveness and side effects of conventional treatments have highlighted the urgent need to develop and identify new adjunct therapeutic strategies. In this work, the results of pain and PGs demonstrated that 850 nm, 630 nm, and 460 nm all exhibited pain inhibition, decreased PGF and upregulated PGE, while 630 nm PBM has better effectiveness. Then to explore the underlying biological mechanisms of red light PBM on PD, we irradiated prostaglandin-F induced HUSM cells and found that low-level irradiance can restore intracellular calcium ion, ROS, ATP, and MMP levels to normal levels. And, red light enhanced cell viability and promoted cell proliferation for normal HUSM cells. Therefore, this study proposes that red light PBM may be a promising approach for the future clinical treatment of PD.
Topics: Dysmenorrhea; Female; Dinoprost; Low-Level Light Therapy; Humans; Cell Survival; Cell Proliferation; Reactive Oxygen Species; Calcium; Cell Line; Adenosine Triphosphate
PubMed: 38348528
DOI: 10.1002/jbio.202300448 -
International Journal of Molecular... Feb 2024Prostaglandins are bioactive compounds, and the activation of their receptors affects the expression of clock genes. However, the prostaglandin F receptor () has no...
Prostaglandins are bioactive compounds, and the activation of their receptors affects the expression of clock genes. However, the prostaglandin F receptor () has no known relationship with biological rhythms. Here, we first measured the locomotor period lengths of (B6.129-) mice and found that they were longer under constant dark conditions (DD) than those of wild-type (C57BL/6J) mice. We then investigated the clock gene patterns within the suprachiasmatic nucleus in mice under DD and observed a decrease in the expression of the clock gene cryptochrome 1 (), which is related to the circadian cycle. Moreover, the expression of , , and () mRNA were significantly altered in the mouse liver in mice under DD. In the wild-type mouse, the plasma prostaglandin F (PGF) levels showed a circadian rhythm under a 12 h cycle of light-dark conditions. In addition, in vitro experiments showed that the addition of PTGFR agonists altered the amplitude of ::luc activity, and this alteration differed with the timing of the agonist addition. These results lead us to hypothesize that the plasma rhythm of PGF is important for driving clock genes, thus suggesting the involvement of PGF- and -targeting drugs in the biological clock cycle.
Topics: Mice; Animals; Dinoprost; Mice, Inbred C57BL; Circadian Rhythm; Biological Clocks; Suprachiasmatic Nucleus; Gene Expression; Cryptochromes
PubMed: 38339119
DOI: 10.3390/ijms25031841 -
BMC Veterinary Research Feb 2024Intrauterine devices (IUD) are used in the veterinary practice as the non-pharmacological method of oestrus suppression in mares. When placed in the uterus, IUD create a...
BACKGROUND
Intrauterine devices (IUD) are used in the veterinary practice as the non-pharmacological method of oestrus suppression in mares. When placed in the uterus, IUD create a physical contact with the endometrium that mimics the presence of an equine embryo. However, the mechanism of their action has not been fully elucidated. The objective of the present study was to examine the effect of mechanical stimulation of IUD on mare`s endometrium in both in vitro and in vivo study. For this purpose, we demonstrated the effect of IUD on prostaglandin (PG) F and PGE secretion, and mRNA transcription of genes involved in PG synthesis pathway in equine endometrial cells in vitro. In the in vivo study, we aimed to compare short-term effect of IUD inserted on day 0 (oestrus) with day 5-6 post-ovulation (the specific time when embryo reaches uterus after fertilization) on PG secretion from equine endometrium. To determine the long-term effect on PG synthase mRNA transcription, a single endometrial biopsy was taken only once within each group of mares at certain time points of the estrous cycle from mares placement with IUD on days 0 or 5-6 post-ovualtion.
RESULTS
We showed for the first time that the incubation of the endometrial cells with the presence of IUD altered the pattern of PG synthase mRNA transcription in equine epithelial and stromal endometrial cells. In vivo, in mares placement with IUD on day 0, PGE concentrations in blood plasma were upregulated between 1 and 6, and at 10 h after the IUD insertion, compared with the control mares (P < 0.05). Moreover, the decrease of PTGFS mRNA transcription on day 16- 18, associated with an elevation in PTGES mRNA transcription on day 20 -21 of the estrous cycle in endometrial biopsies collected from mares placement with IUD on days 5-6 suggest an antiluteolytic action of IUD during the estrous cycle.
CONCLUSION
We conclude that the application of IUD may mimic the equine conceptus presence through the physical contact with the endometrium altering PG synthase transcription, and act as a potent modulator of endometrial PG secretion both in vitro and in vivo.
Topics: Horses; Animals; Female; Dinoprostone; Prostaglandin-Endoperoxide Synthases; Prostaglandins F; Endometrium; Intrauterine Devices; RNA, Messenger
PubMed: 38310284
DOI: 10.1186/s12917-024-03889-0 -
European Journal of Pharmacology Apr 2024Uterine contractions during labor and preterm labor are influenced by a complex interplay of factors, including hormones and inflammatory mediators. This complexity may...
Uterine contractions during labor and preterm labor are influenced by a complex interplay of factors, including hormones and inflammatory mediators. This complexity may contribute to the limited efficacy of current tocolytics for preterm labor, a significant challenge in obstetrics with 15 million cases annually and approximately 1 million resulting deaths worldwide. We have previously shown that the myometrium expresses bitter taste receptors (TAS2Rs) and that their activation leads to uterine relaxation. Here, we investigated whether the selective TAS2R5 agonist phenanthroline can induce relaxation across a spectrum of human uterine contractions and whether the underlying mechanism involves changes in intracellular Ca signaling. We performed experiments using samples from pregnant women undergoing scheduled cesarean delivery, assessing responses to various inflammatory mediators and oxytocin with and without phenanthroline. Our results showed that phenanthroline concentration-dependently inhibited contractions induced by PGF2α, U46619, 5-HT, endothelin-1 and oxytocin. Furthermore, in hTERT-infected human myometrial cells exposed to uterotonics, phenanthroline effectively suppressed the increase in intracellular Ca concentration induced by PGF2α, U46619, oxytocin, and endothelin-1. These results suggest that the selective TAS2R5 agonist may not only significantly reduce uterine contractions but also decrease intracellular Ca levels. This study highlights the potential development of TAS2R5 agonists as a new class of uterine relaxants, providing a novel avenue for improving the management of preterm labor.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Uterine Contraction; Calcium; Oxytocin; Phenanthrolines; Dinoprost; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Endothelin-1; Obstetric Labor, Premature; Myometrium
PubMed: 38281680
DOI: 10.1016/j.ejphar.2024.176343 -
Theriogenology Mar 2024Year 2023 is the 100-year anniversary of the discovery in guinea pigs that the lifespan of the corpus luteum (CL) is controlled by the uterus. The CL is the gatekeeper... (Review)
Review
Year 2023 is the 100-year anniversary of the discovery in guinea pigs that the lifespan of the corpus luteum (CL) is controlled by the uterus. The CL is the gatekeeper between two fundamental reproductive events - the estrous cycle and pregnancy. Uteroluteal research for the initial 33 years was productive but limited to laboratory species until the inclusion of farm animals in 1956. In the early 1960s, it was found that uterine luteolysin in sows travels unilaterally from a uterine horn to the adjacent CL which likely accounted for the heyday of uteroluteal research in the 1960s-70s. The luteolytic properties of PGF2α were demonstrated in rats in 1969. In 1971, (1) surgical separation of the lengthwise adherence between the uteroovarian vein and ovarian artery interfered with luteolysis in ewes, (2) species with primarily unilateral vs systemic uterine-induced luteolysis have a strong vs an absent or weak unilateral venoarterial transfer pathway, and (3) vascular infusions identified PGF2α as a uterine luteolysin. Vascular and PGF2α studies were beginning to merge. In 1973, a venoarterial pathway was firmly demonstrated in ewes and later in heifers by surgical anastomosis of a uterine vein or ovarian artery from a uterine-intact side to the corresponding vessel on the unilaterally hysterectomized side. More recent studies described how prostaglandins likely transfer through the walls of uterine and ovarian vessels using concentration gradients in sows and a prostaglandins transporter system in cows.
Topics: Pregnancy; Animals; Female; Cattle; Sheep; Swine; Rats; Guinea Pigs; Luteolysis; Dinoprost; Corpus Luteum; Uterus; Mammals
PubMed: 38266370
DOI: 10.1016/j.theriogenology.2024.01.014 -
The Journal of Reproduction and... Apr 2024Two studies were conducted to evaluate the effects of the follicular wave on ovarian function and fertility in dairy heifers and lactating cows. In study 1, the estrous...
Two studies were conducted to evaluate the effects of the follicular wave on ovarian function and fertility in dairy heifers and lactating cows. In study 1, the estrous cycle of the selected Holstein heifers was initially synchronized using two intra-muscular prostaglandin F (PGF) administrations 11 days apart. Heifers in group FFW (n = 14) received an intra-muscular 500 μg PGF administration on day 7 after detecting standing estrus, while Heifers in group SFW (n = 14) were administered PGF 13 days after detecting standing estrus. The pregnancy rates of FFW (n = 98) and SFW (n = 100) heifers were also determined 35-37 days after artificial insemination (AI). In Study 2, healthy Holstein lactating cows (n = 28) were randomly assigned to either the FFW (n = 14) or SFW (n = 14) groups. The estrous cycles of the cows were presynchronized using two intra-muscular administrations of PGF given 14 days apart. Then, the emergences of the follicular waves were induced using an Ovsynch protocol. The pregnancy rate of FFW (n = 99) versus SFW (n = 98) cows was also determined 35-37 days after AI. The ovulatory follicle and corpus luteum (CL) resulting from the ovulatory follicle of FFW were larger than those of the dominant follicle and the CL of SFW in dairy heifers and lactating cows. However, the pregnancy rate did not differ between the FFW and SFW groups in heifers and lactating cows 35-37 days after AI. In conclusion, although the characteristics of the ovulatory follicles in FFW versus SFW animals differed, the follicular wave in dairy heifers or lactating cows did not affect fertility.
Topics: Pregnancy; Cattle; Animals; Female; Progesterone; Lactation; Ovarian Follicle; Corpus Luteum; Fertility; Insemination, Artificial; Gonadotropin-Releasing Hormone; Estrus Synchronization; Dinoprost
PubMed: 38246626
DOI: 10.1262/jrd.2023-084 -
Oncology Research 2023Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. Current therapies are effective for HCC patients with early disease, but many patients suffer...
Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. Current therapies are effective for HCC patients with early disease, but many patients suffer recurrence after surgery and have a poor response to chemotherapy. Therefore, new therapeutic targets are needed. We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different. The analysis showed that AKR1C3 was upregulated in tumors, and high AKR1C3 expression was associated with a poorer prognosis in HCC patients. , assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines. Knockdown of AKR1C3 in Huh7 cells reduced tumor growth . To explore the mechanism, we performed pathway enrichment analysis, and the results linked the expression of AKR1C3 with prostaglandin F2 alpha (PGF2α) downstream target genes. Suppression of AKR1C3 activity reduced the production of PGF2α, and supplementation with PGF2α restored the growth of indomethacin-treated Huh7 cells. Knockdown of the PGF receptor (PTGFR) and treatment with a PTGFR inhibitor significantly reduced HCC growth. We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib. In summary, our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α, and suppression of PTGFR limited HCC growth. Therefore, targeting the AKR1C3-PGF2α-PTGFR axis may be a new strategy for the treatment of HCC.
Topics: Humans; Aldo-Keto Reductases; Dinoprost; Carcinoma, Hepatocellular; Liver Neoplasms; Cell Line; Indomethacin; Aldo-Keto Reductase Family 1 Member C3
PubMed: 38188684
DOI: 10.32604/or.2023.030975 -
The Journal of Reproduction and... Feb 2024This study investigated the effects of timed artificial insemination (TAI) and equine chorionic gonadotropin (eCG) administration on lactating dairy cows under...
This study investigated the effects of timed artificial insemination (TAI) and equine chorionic gonadotropin (eCG) administration on lactating dairy cows under heat-stress conditions (average temperature-humidity index: 80). Timed artificial insemination was performed on the cows with (n = 57) or without (control, n = 41) supplementation with 500 IU of eCG at the day of PGF treatment using the CIDR-Ovsynch protocol. GnRH was administered, and a progesterone device (CIDR) was inserted on Day -10 of the treatment protocol. The CIDR was removed on Day -3, and the cows were treated with PGF. Two days later, a 2 GnRH injection was administered. Subsequently, AI was performed on Day 0 (16-20 h after the 2 GnRH injection), and pregnancy was diagnosed on Days 32 and 60. Plasma progesterone (P) concentrations were measured after AI. Results showed that the eCG group had a higher pregnancy per AI (P/AI) than the control group (43.9 vs. 12.2%, P = 0.002), which was also accompanied by elevated P levels. Four cows in the eCG group had multiple calves, representing 7.0 and 16.0% of the group and pregnant cows, respectively. In conclusion, 500 IU of eCG combined with CIDR-Ovsynch in lactating dairy cows under severe heat stress conditions successfully improved fertility. However, the protocol may have a slight risk of multiple births.
Topics: Pregnancy; Female; Cattle; Animals; Horses; Progesterone; Lactation; Dinoprost; Gonadotropin-Releasing Hormone; Estrus Synchronization; Insemination, Artificial; Chorionic Gonadotropin
PubMed: 38171736
DOI: 10.1262/jrd.2023-069 -
Theriogenology Mar 2024The first luteal response to pregnancy in farm animals at 12-18 days after ovulation involves maintenance of the corpus luteum (CL) if pregnancy has occurred. In most... (Review)
Review
The first luteal response to pregnancy in farm animals at 12-18 days after ovulation involves maintenance of the corpus luteum (CL) if pregnancy has occurred. In most common farm species, regression of the CL results from production of a luteolysin (PGF2α) by the nongravid uterus, and maintenance of the CL involves the production of an antiluteolysin (PGE2) by the gravid uterus and conceptus. The proximal component of a unilateral pathway from a uterine horn to the adjacent CL for transport of PGF2α and PGE2 is the uterine venous and lymphatic vessels and the distal component is the ovarian artery. The mechanisms for venolymphatic arterial transport of PGF2α and PGE2 from a uterine horn to the adjacent CL ovary and transfer of each prostaglandin through the walls of the uteroovarian vein and ovarian artery occur by similar mechanisms probably as a consequence of similarities in molecular structure between the two prostaglandins. Reported conclusions or interpretations during the first luteal response to pregnancy in sows and ewes are that PGE2 increases in concentration in the uteroovarian vein and ovarian artery and counteracts the negative effect of PGF2α on the CL. In cows, treatment with PGE2 increases circulating progesterone concentrations and prevents spontaneous luteolysis and luteolysis induced by estradiol, an intrauterine device, or PGF2α. The prevailing acceptance that interferon tau is the primary factor for maintaining the CL during early pregnancy in ruminants will likely become tempered by the increasing reports on PGE2.
Topics: Pregnancy; Animals; Female; Sheep; Swine; Cattle; Animals, Domestic; Dinoprost; Dinoprostone; Corpus Luteum; Luteolysis; Progesterone; Prostaglandins; Ruminants; Lutein
PubMed: 38169182
DOI: 10.1016/j.theriogenology.2023.12.028 -
Mechanisms of acupuncture for primary dysmenorrhea based on PI3K/Akt/mTOR signaling pathway in rats.Zhen Ci Yan Jiu = Acupuncture Research Dec 2023To observe the effect of electroacupuncture(EA) on phosphatidylinositol-3-kinases(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway of...
OBJECTIVES
To observe the effect of electroacupuncture(EA) on phosphatidylinositol-3-kinases(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway of uterus tissue in rats with primary dysmenorrhea(PDM), so as to investigate its mechanisms underlying improvement of PDM.
METHODS
Thirty healthy non-pregnant female SD rats were randomly divided into blank, model and EA groups, with 10 rats in each group. The PDM model was established by subcutaneous injection of estradiol diphenhydrate combined with intraperitoneal injection of oxytocin. For rats of the EA group, EA(50 Hz, a tolerable current intensity) was applied to "Guanyuan"(CV4) and bilateral "Sanyinjiao"(SP6) for 20 min, once a day for 10 consecutive days. The number of writhing, wri-thing score, and writhing latency were observed. The uterine histopathological changes were observed by H.E. staining, and the ultrastructural changes of uterine tissue cells in each group were observed by transmission electron microscopy. The contents of prostaglandin E2(PGE2), prostaglandin F2α(PGF2α) and ratios of PGF2α/PGE2 in the serum and uterine tissue were detected by ELISA. The relative expression levels of PI3K, Akt and mTOR and their phosphorylation proteins in the uterine tissue were detected by Western blot and the ratios were calculated.
RESULTS
Compared with the blank group, the number and score of writhing, latency of writhing, pathological injury score, contents of PGF2α and ratios of PGF2α/PGE2 in the serum and uterine tissue, and the levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in the uterine tissue were significantly increased in the model group(<0.01, <0.05), while contents of PGE2 in the serum and uterine tissue were reduced(<0.05). In comparison with the model group, the number of writhing and writhing score, pathological injury score, contents of PGF2α and ratios of PGF2α/PGE2 in both the serum and uterine tissue, the levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR were obviously decreased(<0.05, <0.01), whereas the writhing latency was considerably prolonged in the EA group(<0.01), with elevated contents of PGE2 in the serum and uterine tissue(<0.05). H.E. staining showed slight dilation of uterine glandular cavity, and severe endometrial edema with extensive cell shedding and a large number of vacuole-like degeneration, apoptosis, pyknosis or fragmentation or disappearance of the nucleus, and neutrophil infiltration in the model group, which were relatively milder in the EA group. Ultrastructural results showed irregular fibroblasts of uterine tissue cells, obvious cytoplasmic edema, reduction in cytoplasmic electron density, seriously irregular nuclei, severe edema of mitochondria with dissolved matrix, fracture and disappearance of mitochondrial crests and vacuolation, and moderate dilation of rough endoplasmic reticulum in the model group, which were milder in the EA group.
CONCLUSIONS
EA can improve pain and uterine inflammatory response in PDM rats, which may be associated with its functions in reducing uterine PGF2α and down-regulating PI3K/Akt/mTOR signaling.
Topics: Humans; Rats; Female; Animals; Rats, Sprague-Dawley; Dysmenorrhea; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Dinoprost; Dinoprostone; Acupuncture Points; Signal Transduction; Electroacupuncture; TOR Serine-Threonine Kinases; Edema; Mammals
PubMed: 38146249
DOI: 10.13702/j.1000-0607.20230007