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Human Reproduction Update Jul 2023Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as... (Review)
Review
BACKGROUND
Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as well as the elimination of infected or damaged cells throughout life. Quality control through regulation of cell death pathways is particularly important in the germline, which is responsible for the generation of offspring. Women are born with their entire supply of germ cells, housed in functional units known as follicles. Follicles contain an oocyte, as well as specialized somatic granulosa cells essential for oocyte survival. Follicle loss-via regulated cell death-occurs throughout follicle development and life, and can be accelerated following exposure to various environmental and lifestyle factors. It is thought that the elimination of damaged follicles is necessary to ensure that only the best quality oocytes are available for reproduction.
OBJECTIVE AND RATIONALE
Understanding the precise factors involved in triggering and executing follicle death is crucial to uncovering how follicle endowment is initially determined, as well as how follicle number is maintained throughout puberty, reproductive life, and ovarian ageing in women. Apoptosis is established as essential for ovarian homeostasis at all stages of development and life. However, involvement of other cell death pathways in the ovary is less established. This review aims to summarize the most recent literature on cell death regulators in the ovary, with a particular focus on non-apoptotic pathways and their functions throughout the discrete stages of ovarian development and reproductive life.
SEARCH METHODS
Comprehensive literature searches were carried out using PubMed and Google Scholar for human, animal, and cellular studies published until August 2022 using the following search terms: oogenesis, follicle formation, follicle atresia, oocyte loss, oocyte apoptosis, regulated cell death in the ovary, non-apoptotic cell death in the ovary, premature ovarian insufficiency, primordial follicles, oocyte quality control, granulosa cell death, autophagy in the ovary, autophagy in oocytes, necroptosis in the ovary, necroptosis in oocytes, pyroptosis in the ovary, pyroptosis in oocytes, parthanatos in the ovary, and parthanatos in oocytes.
OUTCOMES
Numerous regulated cell death pathways operate in mammalian cells, including apoptosis, autophagic cell death, necroptosis, and pyroptosis. However, our understanding of the distinct cell death mediators in each ovarian cell type and follicle class across the different stages of life remains the source of ongoing investigation. Here, we highlight recent evidence for the contribution of non-apoptotic pathways to ovarian development and function. In particular, we discuss the involvement of autophagy during follicle formation and the role of autophagic cell death, necroptosis, pyroptosis, and parthanatos during follicle atresia, particularly in response to physiological stressors (e.g. oxidative stress).
WIDER IMPLICATIONS
Improved knowledge of the roles of each regulated cell death pathway in the ovary is vital for understanding ovarian development, as well as maintenance of ovarian function throughout the lifespan. This information is pertinent not only to our understanding of endocrine health, reproductive health, and fertility in women but also to enable identification of novel fertility preservation targets.
Topics: Adult; Animals; Female; Humans; Apoptosis; Granulosa Cells; Mammals; Oocytes; Ovarian Follicle; Ovary; Regulated Cell Death; Homeostasis
PubMed: 36857094
DOI: 10.1093/humupd/dmad005 -
Cells Jul 2023The current review aims to provide an overview of the most recent research on the potentials of concentrated growth factors used in the maxillary sinus lift technique. (Review)
Review
Maxillary Sinus Augmentation Using Autologous Platelet Concentrates (Platelet-Rich Plasma, Platelet-Rich Fibrin, and Concentrated Growth Factor) Combined with Bone Graft: A Systematic Review.
BACKGROUND
The current review aims to provide an overview of the most recent research on the potentials of concentrated growth factors used in the maxillary sinus lift technique.
MATERIALS AND METHODS
"PRP", "PRF", "L-PRF", "CGF", "oral surgery", "sticky bone", "sinus lift" were the search terms utilized in the databases Scopus, Web of Science, and Pubmed, with the Boolean operator "AND" and "OR".
RESULTS
Of these 1534 studies, 22 publications were included for this review.
DISCUSSION
The autologous growth factors released from platelet concentrates can help to promote bone remodeling and cell proliferation, and the application of platelet concentrates appears to reduce the amount of autologous bone required during regenerative surgery. Many authors agree that growth factors considerably enhance early vascularization in bone grafts and have a significantly positive pro-angiogenic influence in vivo when combined with alloplastic and xenogeneic materials, reducing inflammation and postoperative pain and stimulating the regeneration of injured tissues and accelerating their healing.
CONCLUSIONS
Even if further studies are still needed, the use of autologous platelet concentrates can improve clinical results where a large elevation of the sinus is needed by improving bone height, thickness and vascularization of surgical sites, and post-operative healing.
Topics: Maxillary Sinus; Bone Regeneration; Platelet-Rich Plasma; Intercellular Signaling Peptides and Proteins; Fibrin
PubMed: 37443831
DOI: 10.3390/cells12131797 -
Clinical and Experimental Dermatology Sep 2023Gender-affirming hormone therapy (GAHT) leads to changes in body composition, secondary sex characteristics and in the distribution and pattern of hair growth....
Gender-affirming hormone therapy (GAHT) leads to changes in body composition, secondary sex characteristics and in the distribution and pattern of hair growth. Transgender individuals undergoing GAHT may experience altered hair growth patterns that may be affirming and desirable, or undesirable with a subsequent impact on their quality of life. Given increasing numbers of transgender individuals commencing GAHT worldwide and the clinical relevance of the impact of GAHT on hair growth, we systematically reviewed the existing literature on the impact of GAHT on hair changes and androgenic alopecia (AGA). The majority of studies used grading schemes or subjective measures of hair changes based on patient or investigator's examination. Very few studies used objective quantitative measures of hair parameters but demonstrated statistically significant changes in hair growth length, diameter and density. Feminizing GAHT with estradiol and/or antiandrogens in transgender women may reduce facial and body hair growth and also can improve AGA. Masculinizing GAHT with testosterone in transgender men may increase facial and body hair growth as well as induce or accelerate AGA. The impact of GAHT on hair growth may not align with a transgender person's hair growth goals and specific treatment for AGA and/or hirsutism may be sought. Further research on how GAHT affects hair growth is required.
Topics: Male; Female; Humans; Quality of Life; Hair; Alopecia; Transgender Persons; Testosterone
PubMed: 37311161
DOI: 10.1093/ced/llad203 -
Strahlentherapie Und Onkologie : Organ... Dec 2023Tumor-associated macrophages (TAMs) are the most represented cells of the immune system in the tumor microenvironment (TME). Besides its effects on cancer cells,... (Review)
Review
OBJECTIVE
Tumor-associated macrophages (TAMs) are the most represented cells of the immune system in the tumor microenvironment (TME). Besides its effects on cancer cells, radiation therapy (RT) can alter TME composition. With this systematic review, we provide a better understanding on how RT can regulate macrophage characterization, namely the M1 antitumor and the M2 protumor polarization, with the aim of describing new effective RT models and exploration of the possibility of integrating radiation with other available therapies.
METHODS
A systematic search in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was carried out in PubMed, Google Scholar, and Scopus. Articles from January 2000 to April 2020 which focus on the role of M1 and M2 macrophages in the response to RT were identified.
RESULTS
Of the 304 selected articles, 29 qualitative summary papers were included in our analysis (16 focusing on administration of RT and concomitant systemic molecules, and 13 reporting on RT alone). Based on dose intensity, irradiation was classified into low (low-dose irradiation, LDI; corresponding to less than 1 Gy), moderate (moderate-dose irradiation, MDI; between 1 and 10 Gy), and high (high-dose irradiation, HDI; greater than 10 Gy). While HDI seems to be responsible for induced angiogenesis and accelerated tumor growth through early M2-polarized TAM infiltration, MDI stimulates phagocytosis and local LDI may represent a valid treatment option for possible combination with cancer immunotherapeutic agents.
CONCLUSION
TAMs seem to have an ambivalent role on the efficacy of cancer treatment. Radiation therapy, which exerts its main antitumor activity via cell killing, can in turn interfere with TAM characterization through different modalities. The plasticity of TAMs makes them an attractive target for anticancer therapies and more research should be conducted to explore this potential therapeutic strategy.
Topics: Humans; Tumor-Associated Macrophages; Neoplasms; Macrophages; Tumor Microenvironment
PubMed: 37347290
DOI: 10.1007/s00066-023-02097-3 -
Medicina (Kaunas, Lithuania) Dec 2023: Korean and traditional Chinese medicine state that pyrite is effective for fracture treatment, but supporting clinical data are limited. This systematic review aimed... (Meta-Analysis)
Meta-Analysis Review
: Korean and traditional Chinese medicine state that pyrite is effective for fracture treatment, but supporting clinical data are limited. This systematic review aimed to investigate the therapeutic role of Chinese patent medicine containing pyrite (CPMP) in clinical treatment for fractures. : Seven electronic databases were searched using the keywords "pyrite", "pyritum", and "zirantong" between inception and December 2022, yielding 29 published clinical studies. Randomized controlled trials that included CPMP were considered eligible regardless of the fracture type. Quality assessment and meta-analysis of the included RCTs were also performed. : Most studies showed high heterogeneity (I > 50%) and significant results ( < 0.05). Compared to the results of the control group, CPMP was more effective in terms of the primary outcome related to the efficacy rate, including the total effective rate, callus growth rate, bone union, and edema disappearance time (all < 0.00001) and in terms of secondary outcomes related to pain reduction, namely pain intensity and pain disappearance time, than the control group (both < 0.01). CPMP was more effective than the control group in terms of erythrocyte sedimentation rate ( < 0.01), hematocrit ( < 0.01), erythrocyte aggregation ( < 0.05), and plasma viscosity ( < 0.05). CPMP did not cause serious side effects, and the incidence of complications was significantly less than that in the control group. : CPMP may be a safe and effective alternative treatment for fractures and may be beneficial in preventing postoperative complications, reducing pain, relieving symptoms, and accelerating healing.
Topics: Humans; Fractures, Bone; Medicine, East Asian Traditional; Asian People; Pain; Iron; Sulfides
PubMed: 38256337
DOI: 10.3390/medicina60010076 -
Cell Biochemistry and Function Mar 2024The demand for efficient and accelerated osseointegration in dental implantology has led to the exploration of innovative tissue engineering strategies. Immediate... (Review)
Review
The demand for efficient and accelerated osseointegration in dental implantology has led to the exploration of innovative tissue engineering strategies. Immediate implant loading reduces treatment duration and necessitates robust osseointegration to ensure long-term implant success. This review article discusses the current studies of tissue engineering innovations for enhancing osseointegration in immediate dental implant loading in the recent decade. Keywords "tissue engineering," "osseointegration," "immediate implant loading," and related terms were systematically searched. The review highlights the potential of bioactive materials and growth factor delivery systems in promoting osteogenic activity and accelerating bone regeneration. The in vivo experiment demonstrates significantly improved osseointegration in the experimental group compared to traditional immediate loading techniques, as evidenced by histological analyses and biomechanical assessments. It is possible to revolutionize the treatment outcomes and patient satisfaction in dental implants by integrating bioactive materials and growth factors.
Topics: Humans; Osseointegration; Immediate Dental Implant Loading; Tissue Engineering; Treatment Outcome; Osteogenesis
PubMed: 38491807
DOI: 10.1002/cbf.3974 -
Phytomedicine : International Journal... Apr 2024Stomach diseases have become global health concerns. Protoberberine alkaloids (PBAs) are a group of quaternary isoquinoline alkaloids from abundant natural sources and... (Review)
Review
BACKGROUND
Stomach diseases have become global health concerns. Protoberberine alkaloids (PBAs) are a group of quaternary isoquinoline alkaloids from abundant natural sources and have been shown to improve gastric disorders in preclinical and clinical studies. The finding that PBAs exhibit low oral bioavailability but potent pharmacological activity has attracted great interest.
PURPOSE
This review aims to provide a systematic review of the molecular mechanisms of PBAs in the treatment of gastric disorders and to discuss the current understanding of the pharmacokinetics and toxicity of PBAs.
METHODS
The articles related to PBAs were collected from the Web of Science, Pubmed, and China National Knowledge Infrastructure databases using relevant keywords. The collected articles were screened and categorized according to their research content to focus on the gastroprotective effects, pharmacokinetics, and toxicity of PBAs.
RESULTS
Based on the results of preclinical studies, PBAs have demonstrated therapeutic effects on chronic atrophic gastritis and gastric cancer by activating interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (STAT6) pathway and suppressing transforming growth factor-beta 1 (TGF-β1)/phosphoinositide 3-kinase (PI3K), Janus kinase-2 (JAK2)/signal transducers and activators of transcription 3 (STAT3), and mitogen-activated protein kinase (MAPK) pathways. The major PBAs exhibit similar pharmacokinetic properties, including rapid absorption, slow elimination, and low bioavailability. Notably, the natural organ-targeting property of PBAs may account for the finding of their low blood levels and high pharmacological activity. PBAs interact with other compounds, including conventional drugs and natural products, by modulation of metabolic enzymes and transporters. The potential tissue toxicity of PBAs should be emphasized due to their high tissue accumulation.
CONCLUSION
This review highlights the gastroprotective effects, pharmacokinetics, and toxicity of PBAs and will contribute to the evaluation of drug properties and clinical translational studies of PBAs, accelerating their transfer from the laboratory to the bedside.
Topics: Phosphatidylinositol 3-Kinases; Alkaloids; Berberine Alkaloids; Drugs, Chinese Herbal
PubMed: 38367423
DOI: 10.1016/j.phymed.2024.155444 -
The International Journal of Oral &... Nov 2023The clinical use of bioactive substances, such as growth factors, have significantly increased, however, potential regenerative effects derived from the addition of...
Do recombinant, purified or concentrated growth factors enhance the regenerative potential of particulate bone graft substitutes in maxillary sinus floor augmentation? A systematic review and meta-analysis.
BACKGROUND
The clinical use of bioactive substances, such as growth factors, have significantly increased, however, potential regenerative effects derived from the addition of different growth factors to bone substitutes on maxillary sinus floor augmentation (MSA) procedures is still controversial. This systematic review (SR) aimed at answering the following question: "Do recombinant, purified and concentrated growth factors enhance the regenerative potential of particulate bone graft substitutes in maxillary sinus floor augmentation?".
METHODS
Human studies comparing histomorphometric data of the outcomes of interest new bone formation, residual graft material, and fibrous tissue ratio following MSA procedures employing particulate bone grafts/substitutes in combination or not with growth factors were retrieved from PubMed/MEDLINE, Web of Science, Cochrane and Scopus online databases and complemented with a hand search. Controlled studies published in English up to December 2022 and reporting on histomorphometric data expressed as percent volume of the outcomes of interest were considered. Risk of bias was assessed, and a meta-analysis (MA) was performed to investigate the effects of supplementary growth factors on new bone formation, remaining graft particles and fibrous tissue ratio.
RESULTS
Data of 613 samples from 477 patients reported in 22 publications were included. MA showed PRP or PRF resulted in 49% more new bone formation than in areas in control groups (P=0.004), and those areas supplemented with growth factors presented 57% less residual graft particles after healing (P<0.0001). A significant (P=0.03) 1.85-fold increase in connective tissue formation was noted in areas treated with rhBMP after healing.
CONCLUSION
The MA provided evidence that selective supplementary growth factors may enhance new bone formation and accelerate particulate graft turnover, while rhBMP may significantly increase connective tissue formation in MSA procedures in humans.
PubMed: 37939238
DOI: 10.11607/jomi.10553 -
The Cochrane Database of Systematic... Nov 2023Many infants are fed infant formulas to promote growth. Some formulas have a high protein content (≥ 2.5 g per 100 kcal) to accelerate weight gain during the first... (Review)
Review
BACKGROUND
Many infants are fed infant formulas to promote growth. Some formulas have a high protein content (≥ 2.5 g per 100 kcal) to accelerate weight gain during the first year of life. The risk-benefit balance of these formulas is unclear.
OBJECTIVES
To evaluate the benefits and harms of higher protein intake versus lower protein intake in healthy, formula-fed term infants.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, OpenGrey, clinical trial registries, and conference proceedings in October 2022.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of healthy formula-fed infants (those fed only formula and those given formula as a complementary food). We included infants of any sex or ethnicity who were fed infant formula for at least three consecutive months at any time from birth. We excluded quasi-randomized trials, observational studies, and infants with congenital malformations or serious underlying diseases. We defined high protein content as 2.5 g or more per 100 kcal, and low protein content as less than 1.8 g per 100 kcal (for exclusive formula feeding) or less than 1.7 g per 100 kcal (for complementary formula feeding).
DATA COLLECTION AND ANALYSIS
Four review authors independently assessed the risk of bias and extracted data from trials, and a fifth review author resolved discrepancies. We performed random-effects meta-analyses, calculating risk ratios (RRs) or Peto odds ratios (Peto ORs) with 95% confidence intervals (CIs) for dichotomous outcomes, and mean differences (MDs) with 95% CIs for continuous outcomes. We used the GRADE approach to evaluate the certainty of the evidence.
MAIN RESULTS
We included 11 RCTs (1185 infants) conducted in high-income countries. Seven trials (1629 infants) compared high-protein formula against standard-protein formula, and four trials (256 infants) compared standard-protein formula against low-protein formula. The longest follow-up was 11 years. High-protein formula versus standard-protein formula We found very low-certainty evidence that feeding healthy term infants high-protein formula compared to standard-protein formula has little or no effect on underweight (MD in weight-for-age z-score 0.05 SDs, 95% CI -0.09 to 0.19; P = 0.51, I = 61%; 7 studies, 1629 participants), stunting (MD in height-for-age z-score 0.15 SDs, 95% CI -0.05 to 0.35; P = 0.14, I = 73%; 7 studies, 1629 participants), and wasting (MD in weight-for-height z-score -0.12 SDs, 95% CI -0.31 to 0.07; P = 0.20, I = 94%; 7 studies, 1629 participants) in the first year of life. We found very low-certainty evidence that feeding healthy infants high-protein formula compared to standard-protein formula has little or no effect on the occurrence of overweight (RR 1.26, 95% CI 0.63 to 2.51; P = 0.51; 1 study, 1090 participants) or obesity (RR 1.96, 95% CI 0.59 to 6.48; P = 0.27; 1 study, 1090 participants) at five years of follow-up. No studies reported all-cause mortality. Feeding healthy infants high-protein formula compared to standard-protein formula may have little or no effect on the occurrence of adverse events such as diarrhea, vomiting, or milk hypersensitivity (RR 0.93, 95% CI 0.76 to 1.13; P = 0.44, I = 0%; 4 studies, 445 participants; low-certainty evidence) in the first year of life. Standard-protein formula versus low-protein formula We found very low-certainty evidence that feeding healthy infants standard-protein formula compared to low-protein formula has little or no effect on underweight (MD in weight-for-age z-score 0.0, 95% CI -0.43 to 0.43; P = 0.99, I = 81%; 4 studies, 256 participants), stunting (MD in height-for-age z-score -0.01, 95% CI -0.36 to 0.35; P = 0.96, I = 73%; 4 studies, 256 participants), and wasting (MD in weight-for-height z-score 0.13, 95% CI -0.29 to 0.56; P = 0.54, I = 95%; 4 studies, 256 participants) in the first year of life. No studies reported overweight, obesity, or all-cause mortality. Feeding healthy infants standard-protein formula compared to low-protein formula may have little or no effect on the occurrence of adverse events such as diarrhea, vomiting, or milk hypersensitivity (Peto OR 1.55, 95% CI 0.70 to 3.40; P = 0.28, I = 0%; 2 studies, 206 participants; low-certainty evidence) in the first four months of life.
AUTHORS' CONCLUSIONS
We are unsure if feeding healthy infants high-protein formula compared to standard-protein formula has an effect on undernutrition, overweight, or obesity. There may be little or no difference in the risk of adverse effects between infants fed with high-protein formula versus those fed with standard-protein formula. We are unsure if feeding healthy infants standard-protein formula compared to low-protein formula has any effect on undernutrition. There may be little or no difference in the risk of adverse effects between infants fed with standard-protein formula versus those fed with low-protein formula. The findings of six ongoing studies and two studies awaiting classification studies may change the conclusions of this review.
Topics: Infant; Humans; Milk Hypersensitivity; Overweight; Thinness; Growth Disorders; Obesity; Malnutrition; Diarrhea; Vomiting
PubMed: 37929831
DOI: 10.1002/14651858.CD013758.pub2 -
Cureus Sep 2023The information for protein synthesis is given by the genes. These proteins are responsible for controlling functions like cell growth, differentiation, cell... (Review)
Review
The information for protein synthesis is given by the genes. These proteins are responsible for controlling functions like cell growth, differentiation, cell maturation, and cell death. In the case of genetic mutations, the protein functions get disturbed leading to a drastic shift in the normal physiological functions of cell growth, differentiation, and proliferation, making the normal cell cancerous. The Harvey rat sarcoma virus (HRAS) gene is an oncogene that belongs to the rat sarcoma virus (RAS) family. HRAS gene provides the instructions for making the HRAS protein that plays an important role in regulating cell division and when the HRAS gene gets mutated it gets involved in initiating cancer. HRAS mutation has been frequently noted in head and neck cancers; however, the mechanism of HRAS mutation involved in the initiation of oral squamous cell carcinoma (OSCC) still remains unexplored. An elaborate systematic literature search was done in PubMed, Scopus, and Web of Science databases. It was found that the Ras-dependent mutations affect the involved upstream and downstream components of the Ras-Raf-MAPK (rat sarcoma virus-rapidly accelerated fibrosarcoma-mitogen-activated protein kinase) pathway deregulating the signal leading to tumorigenesis. The Ras mutation can affect the Ras-Raf-MAPK pathway at different stages. The disease caused is based on the frequency of the HRAS mutation and it can lead to diverse cellular outcomes as it is mainly associated with cell division, differentiation, growth, survival, and the cell cycle. The crosstalk between the signaling pathways is controlled by the signaling molecules resulting in the creation of molecular networks. The balance of these molecular networks is very important to determine the cellular outcome. This systematic review inspects the molecular network of HRAS and its vital role in carcinogenesis. It is aimed at exploring and summarizing the contributions of the HRAS mutation involved in the pathogenesis of OSCC.
PubMed: 37868370
DOI: 10.7759/cureus.45505