Overweight and Obesity in Adult Birth by Cesarean Section: A Systematic Review With Meta-analysis.

CONTEXT: Overweight/obesity is one of the most important health problems. Birth by cesarean section has been shown to influence long-term health outcomes including obesity. OBJECTIVE: The aim of this systematic review-meta-analysis is to update acknowledgment of the increased risk of cesarean section on offspring's overweight/obesity. METHODS: This study follows the PRISMA guidelines. A systematic literature search was conducted on Scopus, PubMed, and Web of Science; we have selected all the articles published until January 2, 2022. For inclusion, studies must have reported either (i) both birth by cesarean section and adult (≥18 years) offspring's body mass index; (ii) cohort or case-control study design; and (iii) a risk estimate. Heterogeneity testing was performed using Cochran's Q and I2 statistics. Publication bias was assessed by the Egger test and the Begg test. Meta-analysis was performed through a random-effects model. RESULTS: Twelve studies with a combined population of 180 065 subjects were included in the meta-analysis. The overall analysis (N = 19) yielded a combined risk estimate for overweight/obesity of 1.19 (95% CI, 1.08-1.30) and the test of heterogeneity resulted into Q = 57.44 ( I2 = 68.67%, P ≤ .001). The risk of offspring obesity is 1.23 (95% CI, 1.09-1.39) and the test of heterogeneity resulted into Q = 39.55 ( I2 = 69.66%, P ≤ .001). Children born by cesarean section have an increased risk of obesity in adulthood.

Epigenetic Modifications Induced by Olive Oil and Its Phenolic Compounds: A Systematic Review.

Many studies demonstrated that olive oil (especially extra virgin olive oil: EVOO) phenolic compounds are bioactive molecules with anti-cancer, anti-inflammatory, anti-aging and neuroprotective activities. These effects have been recently attributed to the ability of these compounds to induce epigenetics modifications such as miRNAs expression, DNA methylation and histone modifications. In this study, we systematically review and discuss, following the PRISMA statements, the epigenetic modifications induced by EVOO and its phenols in different experimental systems. At the end of literature search through "PubMed", "Web of Science" and "Scopus", 43 studies were selected.Among them, 22 studies reported data on miRNAs, 15 on DNA methylation and 13 on histone modification. Most of the "epigenomic" changes observed in response to olive oil phenols' exposure were mechanistically associated with the cancer preventive and anti-inflammatory effects. In many cases, the epigenetics effects regarding the DNA methylation were demonstrated for olive oil but without any indication regarding the presence or not of phenols. Overall, the findings of the present systematic review may have important implications for understanding the epigenetic mechanisms behind the health effects of olive oil. However, generally no direct evidence was provided for the causal relationships between epigenetics modification and EVOO health related effects. Further studies are necessary to demonstrate the real physiological consequences of the epigenetics modification induced by EVOO and its phenolic compounds.

The Role of Diet in Osteoporotic Fracture Healing: a Systematic Review.

PURPOSE OF REVIEW: Summarize the in vivo evidences on the association between nutrition and osteoporosis fracture healing. RECENT FINDINGS: Osteoporotic fractures constitute a considerable public health burden. The healing capacity of fractures is influenced by local factors related to the fracture and by general factors (e.g., age, sex, osteoporosis, muscular mass, smoking, alcohol, drugs, and diet). The systematic review was conducted according to PRISMA statement. From the literature search on PubMed and Web of Science, from January 2016 to October 2019, twelve studies were selected and resulted highly variable in samples, exposure, methods, outcomes, and outcome assessment. Eleven studies were conducted on laboratory animals. Only one study aimed to investigate the impact of nutritional status on fracture healing in osteoporotic patients. In this review, the role of calcium/vitamin D supplementation remained controversial, while sialoglycoprotein supplementation, phytoestrogen-rich herb extract, flavonoids, and phosphorylated peptides showed a positive effect on osteoporotic fracture healing.

Antitumoral Properties of Natural Products.

Cancer is one of the major causes of death worldwide [...].

Maternal Folate Intake and Risk of Childhood Brain and Spinal Cord Tumors: A Systematic Review and Meta-Analysis.

BACKGROUND: Many epidemiological studies have investigated the effect of maternal diet and prenatal multivitamin supplementation on pediatric cancer risk. Childhood brain and spinal cord tumors (CBSCT) have been attributed to different possible risk factors. METHODS: We conducted a systematic review and meta-analysis on maternal folate intake before and during pregnancy and the risk of CBSCT. We systematically reviewed publications obtained by searching the Insitute for Scientific Information Web of Knowledge and PubMed literature databases. We extracted the risk estimate of the highest and the lowest reported categories of intake from each study and conducted a meta-analysis using a random-effects model. RESULTS: The results of the pooled analysis of all 10 studies, 1 cohort and 9 case-control studies, indicated that maternal folate intake was inversely associated with CBSCT risk (OR 0.77; 95% CI 0.67-0.88, p < 0.001; I2 = 51.22%, p = 0.001). Separate analyses on the basis of the source of folate (folic acid supplementation, dietary folate) and in relation to the timing of exposure (before pregnancy, during pregnancy) found that folic acid supplementation was associated with an approximately 23% reduction in -CBSCT risk (OR 0.77, 95% CI 0.66-0.90, p = 0.001; I2 = 53.18%, p = 0.001) and consumption during pregnancy was associated with an approximately 20% reduction in CBSCT risk (OR 0.80, 95% CI 0.67-0.97, p = 0.020; I2 = 62.48%, p < 0·001). CONCLUSIONS: Maternal consumption of folic acid is associated with a reduced risk of CBSCT. Further investigations are necessary to increase the reliability of the results and estimate the relationship between dose-response and the best outcome.

Hydroxytyrosol Exerts Anti-Inflammatory and Anti-Oxidant Activities in a Mouse Model of Systemic Inflammation.

Hydroxytyrosol (3,4-dihydroxyphenil-ethanol, HT), the major phenol derived from olive oil consumption, has shown different anti-inflammatory and anti-oxidant activities in vitro which may explain the chronic-degenerative diseases preventive properties of olive oil. The aim of this study was to examine the ability of HT reduce inflammatory markers, Cyclooxygenase-2 (COX2) and Tumour Necrosis Factor alfa (TNF-α and oxidative stress in vivo on a mouse model of systemic inflammation. Balb/c mice were pre-treated with HT (40 and 80 mg/Kg b.w.) and then stimulated by intraperitoneal injection of lipopolysaccharide (LPS). Blood was collected to measure COX2 gene expression by qPCR and TNF-α level by ELISA kit in plasma. In addition, the total anti-oxidant power of plasma and the DNA damage were measured by FRAP test and COMET assay, respectively. LPS increased the COX2 expression, the TNF-α production and the DNA damage. HT administration prevented all LPS-induced effects and improved the anti-oxidant power of plasma. HT demonstrated in vivo anti-inflammatory and anti-oxidant abilities. The results may explain the health effects of olive oil in Mediterranean diet. HT represents an interesting molecule for the development of new nutraceuticals and functional food useful in chronic diseases prevention.

Apple intake and cancer risk: a systematic review and meta-analysis of observational studies.

OBJECTIVE: Conflicting results on the association between fruit consumption and cancer risk have been reported. Little is known about the cancer preventive effects of different fruit types. The present meta-analysis investigates whether an association exists between apple intake and cancer risk. DESIGN: Relevant observational studies were identified by literature search (PubMed, Web of Science and Embase). A random-effect model was used to estimate the cancer risk in different anatomical sites. Between-study heterogeneity and publication bias were assessed using adequate statistical tests. RESULTS: Twenty case-control (three on lung, five on colorectal, five on breast, two on oesophageal, three on oral cavity, two on prostate and one each on pancreas, bladder, larynx, ovary, kidney and brain cancer) and twenty-one cohort (seven on lung, two on colorectal, three on breast and one each on oesophageal, pancreas, bladder, kidney, endometrial, head-neck, urothelial and stomach cancer) studies met the inclusion criteria. Comparing the highest v. lowest level of apple consumption, the reduction of lung cancer risk was statistically highly significant in both case-control (OR=0·75; 95% CI 0·63, 0·88; P=0·001, I 2=0 %) and cohort studies (relative risk=0·89; 95% CI 0·84, 0·94; P<0·001, I 2=53 %). Instead, in the case of colorectal (OR=0·66; 95% CI 0·54, 0·81; P<0·001, I 2=55%), breast (OR=0·79; 95% CI 0·73, 0·87; P<0·001, I 2=1 %) and overall digestive tract (OR=0·50; 95% CI 0·36, 0·69; P<0·001, I 2=90 %) cancers a significant preventive effect of apples was found only in case-control studies while prospective studies indicated no effect. No evidence of publication bias could be detected for colorectal, oral cavity, oesophageal and breast cancer. However, some confounding effects may be present and related to the consumption of other fruit which have not been considered as adjusting factors. CONCLUSIONS: The present meta-analysis indicates that consumption of apples is associated with a reduced risk of cancer in different anatomical sites.

Garlic consumption and colorectal cancer risk in man: a systematic review and meta-analysis.

OBJECTIVE: Colorectal cancer shows large incidence variations worldwide that have been attributed to different dietary factors. We conducted a meta-analysis on the relationship between garlic consumption and colorectal cancer risk. DESIGN: We systematically reviewed publications obtained by searching ISI Web of Knowledge, MEDLINE and EMBASE literature databases. We extracted the risk estimate of the highest and the lowest reported categories of intake from each study and conducted meta-analysis using a random-effects model. RESULTS: The pooled analysis of all fourteen studies, seven cohort and seven case-control, indicated that garlic consumption was not associated with colorectal cancer risk (OR=0·93; 95 % CI 0·82, 1·06, P=0·281; I 2=83·6 %, P≤0·001). Separate analyses on the basis of cancer sites and sex also revealed no statistically significant effects on cancer risk. However, when separately analysed on the basis of study type, we found that garlic was associated with an approximately 37 % reduction in colorectal cancer risk in the case-control studies (combined risk estimate=0·63, 95 % CI 0·48, 0·82, P=0·001; I 2=75·6 %, P≤0·001). CONCLUSIONS: Our results suggest that consumption of garlic is not associated with a reduced colorectal cancer risk. Further investigations are necessary to clarify the discrepancy between results obtained from different types of epidemiological studies.

Preventive activity of olive oil phenolic compounds on alkene epoxides induced oxidative DNA damage on human peripheral blood mononuclear cells.

The aim of this study was to investigate the ability of epoxides of styrene (styrene-7,8-oxide; SO) and 1,3-butadiene (3,4-epoxy-1-butene; 1,2:3,4:-diepoxybutane) to cause oxidative stress and oxidative DNA damage on human peripheral blood mononuclear cells (PBMCs) and whether a complex mixture of olive oil phenols (OOPE) could prevent these effects. The DNA damage was measured by the single-cell gel electrophoresis (SCGE; comet assay). We found that the DNA damage induced by alkene epoxides could be prevented by N-acetyl-cysteine (10 mM) and catalase (100 U/ml). Alkene epoxides caused a significant (P < 0.05) increase of both peroxide concentration in extra- and intracellular environment and formamidopyrimidine DNA glycosylase (FPG)- and Endonuclease III (ENDO III)-sensitive sites in PBMCs, demonstrating the presence of oxidized bases. OOPE (1 µg of total phenols/ml) was able to prevent the alkene epoxide induced DNA damage both after 2 and 24 h of incubation. In addition, OOPE completely inhibited the SO-induced intracellular peroxide accumulation in PBMCs and prevented the oxidative DNA damage induced by SO, as evidenced by the disappearance of both FPG- and ENDO III-sensitive sites. This is the first study demonstrating the ability of OOPE to prevent the DNA damage induced by alkene epoxides providing additional information about the chemopreventive properties of olive oil.

Benzene Exposure and Lung Cancer Risk: A Systematic Review and Meta-Analysis of Human Studies.

Lung cancer is a leading cause of death with nearly 1.8 million deaths estimated worldwide in 2020. Although benzene is classified as a human carcinogen (Group 1) on the basis of its association with acute myeloid/non-lymphocytic leukaemia, there is still limited evidence that it may influence lung cancer risk. This study examined the potential link between benzene exposure and risk of lung cancer using a systematic review of epidemiological studies and meta-analysis. We searched through PubMed, Web of Science and Scopus databases up to 10 February 2023 to identify all articles on the association between benzene exposure and lung cancer (incidence or prevalence) and/or mortality. We extracted the risk estimates of the highest and the lowest reported categories of benzene exposure and conducted a meta-analysis using a random-effects model. Heterogeneity and publication bias were analysed using an I2 test and funnel plots asymmetry, respectively. Twenty-one studies were included in the final analysis, with a total of 10,750 lung cancer cases and 2899 lung cancer deaths. Overall, risk estimates of lung cancer prevalence and mortality in association with benzene exposure were 1.20 (n = 14; 95% CI 1.05-1.37) and 1.15 (n = 13; 95% CI 1.02-1.30), respectively. In all cases, heterogeneity was quite large, while no significant publication bias was observed. When only studies that adjusted for smoking habit were selected, the risk for lung cancer increased by up to 34% (n = 9; 95% CI 1.10-1.64). Our data, which show a strong association between benzene exposure and lung cancer risk, may have important public health implications. However, further studies are needed to identify the lung cancer risk associated with benzene exposure considering different smoking conditions.

Effects of Phenols from Olive Vegetation Water on Mutagenicity and Genotoxicity of Stored-Cooked Beef Patties.

This explorative study aimed to assess the mutagenicity and genotoxicity of stored-cooked beef patties formulated with and without phenols (7.00 mg of phenols/80-g patty) extracted from olive vegetation water (OVW), as related to the formation of cholesterol oxidation products (COPs) and heterocyclic amines (HCAs). The patties were packaged in a modified atmosphere, sampled during cold storage (4 °C) for 9 days, and grilled at 200 °C. The genotoxicity was evaluated by the Comet assay. The patty extract was found to be genotoxic on primary peripheral blood mononuclear cells (PBMCs), while no mutagenicity was detected. The addition of OVW phenols significantly decreased the genotoxicity of the patty extract and reduced the total COPs content in stored-cooked patties (4.59 times lower than control); however, it did not affect the content of total HCAs (31.51-36.31 ng/patty) and the revertants' number. Therefore, these results demonstrate that the OVW phenols were able to counteract the formation of genotoxic compounds in stored-cooked beef patties.

Pinoresinol inhibits proliferation and induces differentiation on human HL60 leukemia cells.

Pinoresinol (PIN), one of the simplest lignans, is the precursor of other dietary lignans that are present in whole-grain cereals, legumes, fruits, and other vegetables. Several experimental and epidemiological evidences suggest that lignans may prevent human cancer in different organs. In this study we investigated the chemopreventive properties of PIN on cell lines derived from different sites either expressing or not the functional tumor suppressor protein p53. It was found that PIN inhibited the proliferation of p53 wild type colon and prostate tumor cells (HCT116 and LNCaP) while in breast cells the inhibition of growth was observed only in p53 mutant cells (MDA-MB-231). A potent antiproliferative activity of PIN was also observed on p53 null cells HL60 (IC50% 8 µM), their multidrug resistant variant HL60R (IC50% 32 µM) and K562. On HL60 cells, PIN caused a block of cell cycle in the G0/G1 phase, induced a weak proapoptotic effect but it was a good trigger of differentiation (NBT reduction and CD11b expression). PIN caused an upregulation of the CDK inhibitor p21(WAF1/Cip1) both at mRNA and protein levels so suggesting that this could be a mechanism by which PIN reduced proliferation and induced differentiation on HL60 cells.

Hysterectomy and thyroid cancer risk: A systematic review and meta-analysis.

Background: Incidence rates of thyroid cancer have increased. Recent studies findings suggest that women who underwent a hysterectomy have an elevated relative risk of thyroid cancer. The aim of our meta-analysis is to summarize the evidence about the association between hysterectomy and thyroid cancer risk. Methods: PubMed, Web of Science, and Scopus database were searched for studies published up to 5 September 2023. The PRISMA statement was followed. Heterogeneity was explored with Q statistic and the I2 statistic. Publication bias was assessed with Begg's and Egger's tests. Results: Sixteen studies met the criteria. The pooled analysis showed a significantly 64% increment of thyroid cancer risk in association with any hysterectomy (OR 1.64, 95% CI 1.48-1.81; I2 = 28.68%, p = 0.156). Hysterectomy without oophorectomy was a stronger predictor of risk than hysterectomy with oophorectomy. The pooled analysis of data regarding hysterectomy without oophorectomy showed a statistically significant increment of thyroid cancer risk by 59%. Hysterectomy with oophorectomy was associated with an increase of thyroid cancer risk of 39% (OR 1.39, 95% CI 1.16-1.67; I2 = 42.10%, p = 0.049). Significant publication bias was not detected. Conclusions: Our findings help with decision making around these surgeries.

Adherence to Data-Driven Dietary Patterns and Lung Cancer Risk: A Systematic Review and Dose-Response Meta-Analysis.

The effect of dietary patterns on lung cancer risk is currently debated. In this study, we evaluated the association between different "a posteriori" dietary patterns and lung cancer risk. The search was carried out (February 2023) through Scopus, Web of Science, and PubMed databases. Meta-analysis was performed by a random-effects model using risk values (RR and OR) extracted from the 12 selected studies. Two main dietary patterns were identified and named "Western/meat" and "Healthy/prudent". The highest adherence to the "Western/meat" dietary pattern significantly increased the lung cancer risk (OR = 1.39; 95% CI: 1.17-1.65; p = 0.0002) while the highest adherence to the "Healthy/prudent" pattern reduced it (OR = 0.65; 95% CI: 0.51-0.83; p = 0.001). A linear trend between both dietary patterns and lung cancer risk was observed. However, a statistically significant inverse dose-response trend was found only for the "Healthy/prudent" dietary pattern (regression coefficient = -0.0031, p = 0.003). Subgroup analyses showed that the "Western/meat" pattern significantly increased the lung cancer risk in former (n = 4) (OR = 1.93, 95% CI: 1.11-3.36) and current smokers (n = 7) (OR = 1.35, 95% CI: 1.06-1.71). Similarly, the "Healthy/prudent" pattern exerts a protective effect on former (n = 4) (OR = 0.61, 95% CI: 0.44-0.85) and current smokers (n = 8) (OR = 0.64, 95% CI: 0.46-0.88). For both dietary patterns, no significant effect was observed on never-smokers.

Anti-proliferative and pro-apoptotic activities of hydroxytyrosol on different tumour cells: the role of extracellular production of hydrogen peroxide.

PURPOSE: Several recently published data suggest that the anti-proliferative and pro-apoptotic properties of hydroxytyrosol [3,4-dihydroxyphenyl ethanol (3,4-DHPEA)] on HL60 cells may be mediated by the accumulation of hydrogen peroxide (H2O2) in the culture medium. The aim of this study was to clarify the role played by H2O2 in the chemopreventive activities of 3,4-DHPEA on breast (MDA and MCF-7), prostate (LNCap and PC3) and colon (SW480 and HCT116) cancer cell lines and to investigate the effects of cell culture medium components and the possible mechanisms at the basis of the H2O2-producing properties of 3,4-DHPEA. METHODS: The proliferation was measured by the MTT assay and the apoptosis by both fluorescence microscopy and flow cytometry. The concentration of H2O2 in the culture medium was measured by the ferrous ion oxidation-xylenol orange method. RESULTS: It was found that the H2O2-inducing ability of 3,4-DHPEA is completely prevented by pyruvate and that the exposure of cells to conditions not supporting the H2O2 accumulation (addition of either catalase or pyruvate to the culture medium) inhibited the anti-proliferative effect of 3,4-DHPEA. Accordingly, the sensitivity of the different cell lines to the anti-proliferative effect of 3,4-DHPEA was inversely correlated with their ability to remove H2O2 from the culture medium. With regard to the mechanism by which 3,4-DHPEA causes the H2O2 accumulation, it was found that superoxide dismutase increased the H2O2 production while tyrosinase, slightly acidic pH (6,8) and absence of oxygen (O2) completely prevented this activity. In addition, different transition metal-chelating compounds did not modify the H2O2-producing activity of 3,4-DHPEA. CONCLUSIONS: The pro-oxidant activity of 3,4-DHPEA deeply influences its 'in vitro' chemopreventive activities. The main initiation step in the H2O2-producing activity is the auto-oxidation of 3,4-DHPEA by O2 with the formation of the semiquinone, superoxide ions (O2(-)) and 2H(+).

Genotoxicity of alkene epoxides in human peripheral blood mononuclear cells and HL60 leukaemia cells evaluated with the comet assay.

Volatile organic compounds (VOCs) exert their carcinogenic activity through the production of epoxide metabolites. Because of their high reactivity some epoxides are also produced in the chemical industry for the synthesis of other compounds. Therefore, human exposure to VOCs epoxides does occur and may be an important human health concern. In this study, the in vitro genotoxic potential of epoxides originating from 1,3-butadiene (3,4-epoxy-1-butene: EB; 1,2:3,4-diepoxybutane: DEB), isoprene (3,4-epoxy-2-methyl-1-butene: IO), styrene (styrene-7,8-oxide: SO), propylene (propylene oxide: PO) and 1-butene (1,2-epoxy-butane: BO) in human peripheral blood mononuclear cells (PBMCs) and promyelocytic leukaemia cells (HL60) was measured with the comet assay (single-cell gel electrophoresis, SCGE). The effect of inclusion of foetal calf serum (FCS, 5%) in the cell-culture medium and different durations of exposure (2h, 24h) were also investigated. All epoxides tested produced DNA damage in a concentration range that did not reduce cell viability. HL60 cells were more resistant than PBMCs to the DNA damage induced by the different epoxides. With the exception of IO, the treatment for 24h resulted in an increase of DNA damage. FCS slightly protected PBMCs from the genotoxic effects induced by IO and BO, whilst no such effect was noted for the other compounds. Overall, the dose-dependent effects that were seen allowed us to define a genotoxicity scale for the different epoxides as follows: SO>EB>DEB>IO>PO>BO, which is in partial agreement with the International Agency for Research on Cancer (IARC) classification of the carcinogenic hazards.

Exogenous Hormone Factors in Relation to the Risk of Malignant Melanoma in Women: A Systematic Review and Meta-Analysis.

The influence of exogenous female hormones on the risk of developing malignant melanoma in women remains controversial. The aim of our review and meta-analysis is to summarize the evidence and derive a more accurate estimation of the association between oral contraceptives (OCs) or menopausal hormone therapy (MHT) and the risk of developing malignant melanoma in women. PubMed, Web of Science, and Scopus database were searched for studies published up until October 2021. The PRISMA statement and MOOSE guidelines were followed. Studies were pooled using a random effects model. Heterogeneity was explored with the chi-square-based Cochran's Q statistic and the I2 statistic. Publication bias was assessed with Begg's test and Egger's test. Forty-six studies met the eligibility criteria. The pooled analysis (26 studies) on OC use and the risk of developing cutaneous malignant melanoma (CMM) showed no significant association, but demonstrated significant association for cohort studies (OR 1.08, 95% CI 1.01-1.16; I2 = 0.00%, p = 0.544). The pooled analysis (16 studies) showed a significantly increased risk of CMM in association with MHT (OR 1.15, 95% CI 1.08-1.23; I2 = 25.32%, p = 0.169). Stratifying the results by study design showed that a significant increased risk of CMM was associated with MHT in the cohort studies (OR 1.12; 95% CI 1.04-1.19; I2 = 0%, p = 0.467). No significant publication bias could be detected. Further studies are needed to investigate the potential association with formulation, duration of use, and dosage of use, and to better understand the role of possible confounders.