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Systematic review: The gut microbiota as a link between colorectal cancer and obesity

OBESITY REVIEWS 2025年第4期26卷 e13872页

作者： Ruiz-Malagon, Antonio Jesus Rodriguez-Sojo, Maria Jesus Redondo, Eduardo Rodriguez-Cabezas, Maria Elena Galvez, Julio Rodriguez-Nogales, Alba Univ Granada Ctr Biomed Res CIBM Dept Pharmacol Granada 18071 Spain Inst Invest Biosanit Granada Ibs GRANADA Granada Spain Inst Invest Biomed Malaga IBIMA Malga Spain Hosp Univ Virgen Las Nieves Serv Digest Granada Spain

Microbiome modulation is one of the novel strategies in medicine with the greatest future to improve the health of individuals and reduce the risk of different conditions, including metabolic, immune, inflammatory, and degenerative diseases, as well as cancer. Regarding the latter, many studies have reported the role of the gut microbiome in carcinogenesis, formation and progression of colorectal cancer (CRC), as well as its response to different systemic therapies. Likewise, obesity, one of the most important risk factors for CRC, is also well known for its association with gut dysbiosis. Moreover, obesity and CRC display, apart from microbial dysbiosis, chronic inflammation, which participates in their pathogenesis. Although human and murine studies demonstrate the significant impact of the microbiome in regulating energy metabolism and CRC development, little is understood about the contribution of the microbiome to the development of obesity-associated CRC. Therefore, this systematic review explores the evidence for microbiome changes associated with these conditions and hypothesizes that this may contribute to the pathogenesis of obesity-related CRC. Two databases were searched, and different studies on the relationship among obesity, intestinal microbiota and CRC in clinical and preclinical models were selected. Data extraction was carried out by two reviewers independently, and 101 studies were finally considered. Findings indicate the existence of a risk association between obesity and CRC derived from metabolic, immune, and microbial disorders.

关键词： colitis colorectal cancer microbiota obesity

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Plant-Derived Molecules Modulate Multidrug resistance in Gastrointestinal Cancers: A Comprehensive Review

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APPLIED SCIENCES-BASEL 2025年第3期15卷 1125-1125页

作者： Perazzoli, Gloria Mesas, Cristina Quinonero, Francisco Doello, Kevin Pena, Mercedes Cepero, Ana Rodriguez-Criado, Jorge Prados, Jose Melguizo, Consolacion Univ Granada Inst Biopathol & Regenerat Med IBIMER Ctr Biomed Res CIBM Granada 18100 Spain Biosanit Inst Granada ibs GRANADA Granada 18014 Spain Univ Granada Fac Med Dept Anat & Embryol Granada 18071 Spain Virgen de las Nieves Hosp Med Oncol Serv Granada 18014 Spain

Multidrug resistance (MDR) development against cytotoxic drugs by tumor cells is one of the main causes of treatment failure in gastrointestinal cancers, a group of cancers of great relevance due to their prevalence and/or mortality. This phenomenon is mediated by diverse mechanisms, including the overexpression of members of the superfamily of membrane transporters of the ATP-binding cassette (ABC). Most of these molecules, including P-glycoprotein (P-gp or MDR1/ABCB), MDR-associated protein 1 (MRP1/ABCC1), MRP2, and breast cancer resistance protein (BCRP/ABCG2), are integrated in the cell membrane, acting as drug efflux pumps. Despite the use of various MDR modulators as adjuvants to improve the chemotherapy response, the results have not been satisfactory. Natural products from plants, such as flavonoids, alkaloids, terpenoids, and coumarins, are capable of modifying drug resistance, suggesting an improvement in the antitumoral effect of the current treatments without generating side effects. This review aims to provide an overview of the most recent studies in relation to plant-derived molecules and extracts that modulate resistance to antitumor drugs and that could be applied in the future in clinical practice to improve the treatment of patients with gastrointestinal cancer.

关键词： multidrug resistance gastrointestinal cancer natural products biomolecules

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Novel cisplatin-magnetoliposome complex shows enhanced antitumor activity via Hyperthermia

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SCIENTIFIC REPORTS 2025年第1期15卷 1-14页

作者： Jimenez-Lopez, M. Carmen Moreno-Maldonado, Ana Carolina Martin-Morales, Natividad O'Valle, Francisco Ibarra, M. Ricardo Goya, Gerardo F. Molina, Ignacio J. Univ Granada Inst Biopathol & Regenerat Med Ctr Biomed Res Hlth Sci Technol Pk Granada Spain Univ Zaragoza Inst Nanosci & Mat Aragon CSIC Zaragoza Spain Inst Invest Biosanit Ibs GRANADA Granada Spain

There are several methods to improve cancer patient survival rates by inducing hyperthermia in tumor tissues, which involves raising their temperature above 41 degrees C. These methods utilize different energy sources to deliver heat to the target region, including light, microwaves or radiofrequency electromagnetic fields. We have developed a new, magnetically responsive nanocarrier, consisting of liposomes loaded with magnetic nanoparticles and cis-diamminedichloroplatinum (II) (CDDP), commonly known as Cisplatin. The resulting magnetoliposome (ML) is rapidly internalized by lung and pancreas tumor cell lines, stored in intracellular vesicles, and capable of inducing hyperthermia under magnetic fields. The ML has no significant toxicity both in vitro and in vivo and, most importantly, enhances cell death by apoptosis after magnetic hyperthermia. Remarkably, mice bearing induced lung tumors, treated with CDDP-loaded nanocarriers and subjected to an applied electromagnetic field, showed an improved survival rate over those treated with either soluble CDDP or hyperthermia alone. Therefore, our approach of magnetic hyperthermia plus CDDP-ML significantly enhances in vitro cell death and in vivo survival of treated animals.

关键词： Magnetoliposomes Magnetic hyperthermia Cis-diamminedichloroplatinum (II) CDDP Lung tumor Pancreas tumor

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Trends in chronic neck and low back pain prevalence in Spain (2006-2020): differences by sex, age, and social class

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EUROPEAN SPINE JOURNAL 2025年第4期34卷 1331-1340页

作者： Huerta, Miguel a. Salazar, Alejandro Moral-Munoz, Jose A. Univ Granada Dept Pharmacol Granada Spain Univ Granada Neurosci Inst Biomed Res Ctr Granada Spain Biosanit Res Inst ibs GRANADA Granada Spain Univ Cadiz Dept Stat & Operat Res Cadiz Spain Biomed Res & Innovat Inst Cadiz INiBICA Cadiz Spain Univ Cadiz Grunenthal Fdn Observ Pain Cadiz Spain Univ Cadiz Dept Nursing & Physiotherapy Cadiz Spain

PurposeTo analyze the evolution of chronic neck and low back pain prevalence in the general Spanish population (>= 15 years) from 2006 to 2020, examining differences by sex, age, social class, and the potential influence of the COVID-19 *** repeated cross-sectional observational study was conducted based on data from six health surveys conducted in Spain between 2006 and 2020, with samples ranging from 21,007 to 29,478 subjects per survey, reported by the European Statistical System and the National Statistical institute. Overall and specific prevalence rates were calculated, and linear trends were assessed over time. The potential influence of the COVID-19 pandemic was evaluated using the Mann-Kendall test, along with prevalence forecasts up to 2020, derived from S-curve *** 2006 and 2020, the prevalence of chronic neck pain ranged from 23.64 to 12.3%, while chronic low back pain ranged from 24.01 to 14.73%. A decreasing trend was observed in both conditions, slightly more pronounced for neck pain. This trend persisted even when excluding 2020 data, which was potentially influenced by the COVID-19 pandemic, and was independent of health surveys. Forecasts indicated that the actual 2020 prevalence rates were lower (by 3.1-4.4%) than predicted. The prevalence was consistently higher among women, older individuals, and lower social classes, though all subgroups showed similar decreasing *** prevalence of chronic neck and low back pain in the Spanish population declined between 2006 and 2020. Subgroup analyses revealed consistent decreases across sex, age, and social class. The COVID-19 pandemic may have impacted the 2020 prevalence rates.

关键词： Epidemiology Low back pain Neck pain Social determinants Chronic disease COVID-19

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Interventions for recurrent embryo implantation failure: An umbrella review

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INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS 2025年第2期169卷 539-556页

作者： Almohammadi, Abdulla Choucair, Fadi Khan, Khalid S. Bueno-Cavanillas, Aurora Cano-Ibanez, Naomi Sidra Med Reprod Med Unit Al Luqta St Doha Qatar Univ Granada Fac Med Dept Prevent Med & Publ Hlth Granada Spain Consortium Biomed Res Epidemiol & Publ Hlth CIBERE Granada Spain Inst Biosanit Res IBs Granada Spain

BackgroundRecurrent implantation failure (RIF) has a multifactorial etiology. An umbrella review was undertaken to evaluate the multiple proposed *** summarize and assess the strength of evidence of interventions for RIF from published systematic reviews (SR) of randomized clinical trials (RCTs).Search StrategyAfter prospective registration (PROSPERO CRD42023414255), a systematic search was conducted in the Cochrane Library, Scopus and Medline from inception until March *** CriteriaSRs of RCTs, with or without meta-analyses (MA), were included if they reported clinical pregnancy rates (CPR) or live birth rates (LBR).Data Collection and AnalysisThe methodological quality of the included SRs was appraised independently in duplicate using the AMSTAR 2 tool. For each intervention, the MAs of RCTs with statistically significant improvements were counted as a percentage of the total assessing the strength of evidence using the GRADE *** resultsA total of 47 SRs were included: 32 reviews covered immunomodulatory interventions, 10 (68 RCTs) covered uterine and endometrial interventions, one covered antibiotics, and four (69 RCTs) addressed mixed approaches, including laboratory interventions. AMSTAR 2 appraised 41 (88%) SRs as critically low or low, and 6 (12%) as moderate or high in quality. The SRs often had a level of overlap of RCTs (median 33.3%), inconsistent definitions of RIF, and varied comparisons for the interventions. Considering the significant meta-analytic evidence of high-moderate GRADE strength: Granulocyte colony-stimulating factor (G-CSF) showed improvement in CPR in 9/13 (69.2%) MAs and LBR in 1/7 (14%);intralipid infusion showed improvement in CPR in 4/6 (57.14%) MAs and LBR in 3/4 (75%);peripheral blood mononuclear cells (PBMC) showed improvement in CPR in 4/8 (50%) MAs and LBR 3/5 (60%);platelet-rich plasma (PRP) intervention showed improvement in CPR in 6/10 (60%) MAs and LBR in 1/5 (20%);human chorionic gona

关键词： assisted reproductive technologies live birth meta-analysis pregnancy randomized controlled trial recurrent implantation failure

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Protective Effect of Dietary Fiber on Blood Pressure and Vascular Dysfunction Through Regulation of Sympathetic Tone and Immune response in Genetic Hypertension

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PHYTOTHERAPY resEARCH 2025年第4期39卷 1858-1875页

作者： Gonzalez-Correa, Cristina Moleon, Javier Minano, Sofia Robles-Vera, Inaki de la Visitacion, Nestor Guerra-Hernandez, Eduardo Toral, Marta Jimenez, Rosario Duarte, Juan Romero, Miguel Univ Granada Ctr Biomed Res CIBM Sch Pharm Dept Pharmacol Granada Spain Inst Invest Biosanit Granada Ibs GRANADA Granada Spain Ctr Nacl Invest Cardiovasc CNIC Madrid Spain Univ Granada Dept Nutr & Bromatol Granada Spain Ciber Enfermedades Cardiovasc CIBERCV Madrid Spain

The mechanisms underlying the antihypertensive effect of dietary fibers remain poorly understood. This study investigates whether dietary fiber supplementation can prevent cardiovascular damage and high blood pressure in a genetic model of neurogenic hypertension. Six-week-old male spontaneously hypertensive rats (SHR) and their respective normotensive control, Wistar Kyoto rats (WKY), were divided into four groups: Untreated WKY, untreated SHR, SHR treated with resistant starch (SHR + RS), and SHR treated with inulin-type fructans (SHR + ITF) for 12 weeks. Additionally, a faecal microbiota transplantation (FMT) experiment was conducted, transferring faecal content from treated SHR donors to recipient SHRs. A diet rich in RS fiber reduced vascular oxidative stress, inflammation, and high blood pressure. These protective effects were associated with a reshaped gut microbiota, leading to increased short-chain fatty acid production, reduced endotoxemia, decreased sympathetic activity, and a restored balance between Th17 and Treg lymphocytes in mesenteric lymph nodes and aorta. Elevated plasma levels of acetate and butyrate in the SHR + RS group correlated with increased expression of aortic GPR41, GRP43 and PPAR delta. Conversely, ITF treatment failed to prevent hypertension or endothelial dysfunction in SHR. FMT from the SHR + RS group to recipient SHR partially replicated these beneficial effects. This study highlights the antihypertensive benefits of dietary insoluble RS fiber, which are attributed to enhanced short-chain fatty acids production in the gut. This leads to improved gut permeability, reduced sympathetic tone, and diminished vascular T-cell accumulation. Therefore, dietary interventions with RS fiber may offer promising therapeutic strategies for preventing hypertension.

关键词： dietary fiber endothelial dysfunction gut dysbiosis gut sympathetic tone hypertension immune system

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Specific microbiome patterns and their association with breast cancer: the intestinal microbiota as a potential biomarker and therapeutic strategy

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CLINICAL & TRANSLATIONAL ONCOLOGY 2025年第1期27卷 15-41页

作者： Amaro-da-Cruz, Alba Rubio-Tomas, Teresa Alvarez-Mercado, Ana I. Univ Granada Fac Sci Dept Chem Engn Granada 18071 Spain Fdn Res & Technol Hellas Inst Mol Biol & Biotechnol Iraklion Crete Greece Complejo Hosp Univ Granada Inst Invest Biosanit Ibs GRANADA Granada 18014 Spain Univ Granada Inst Nutr & Food Technol Biomed Res Ctr Armilla 18016 Spain Univ Granada Sch Pharm Dept Pharmacol Granada 18071 Spain

Breast cancer (BC) is one of the most diagnosed cancers in women. Based on histological characteristics, they are classified as non-invasive, or in situ (tumors located within the milk ducts or milk lobules) and invasive. BC may develop from in situ carcinomas over time. Determining prognosis and predicting response to treatment are essential tools to manage this disease and reduce its incidence and mortality, as well as to promote personalized therapy for patients. However, over half of the cases are not associated with known risk factors. In addition, some patients develop resistance to treatment and relapse. Therefore, it is necessary to identify new biomarkers and treatment strategies that improve existing therapies. In this regard, the role of the microbiome is being researched as it could play a role in carcinogenesis and the efficacy of BC therapies. This review aims to describe specific microbiome patterns associated with BC. For this, a literature search was carried out in PubMed database using the MeSH terms "Breast Neoplasms" and "Gastrointestinal Microbiome", including 29 publications. Most of the studies have focused on characterizing the gut or breast tissue microbiome of the patients. Likewise, studies in animal models and in vitro that investigated the impact of gut microbiota (GM) on BC treatments and the effects of the microbiome on tumor cells were included. Based on the results of the included articles, BC could be associated with an imbalance in the GM. This imbalance varied depending on molecular type, stage and grade of cancer, menopause, menarche, body mass index, and physical activity. However, a specific microbial profile could not be identified as a biomarker. On the other hand, some studies suggest that the GM may influence the efficacy of BC therapies. In addition, some microorganisms and bacterial metabolites could improve the effects of therapies or influence tumor development.

关键词： Breast cancer Microbiome Biomarkers Therapy Microbiota Chemotherapy

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Advances in the use of nanoparticles for specific cell-target delivery of anti-cancer agents

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LIFE SCIENCES 2025年 371卷 123604页

作者： Diaz-Ruano, Ana Belen Gomez-Jimenez, Eliana Llamas-Jimenez, Gloria Ramirez-Munoz, Arena Espejo-Hijano, Pablo Rubio-Navarro, Alfonso Picon-Ruiz, Manuel Univ Granada Univ Hosp Granada Inst Invest Biosanit ibs GRANADA Granada 18100 Spain Univ Granada Biopathol & Regenerat Med Inst IBIMER Ctr Biomed Res CIBM Granada 18100 Spain Univ Granada Fac Med Dept Human Anat & Embryol Granada 18016 Spain Univ Granada Excellence Res Unit Modeling Nat MNat Granada 18100 Spain Univ Granada Fac Med Dept Biochem & Mol Biol & Immunol 3 Granada 18016 Spain

In recent decades, cancer has emerged as one of the leading causes of death in developed countries. To revert this progression, scientists have focused on the design of new strategies for early detection of this disease and the development of more effective treatments for its eradication. Regarding the latter, one of the main research efforts has been directed toward designing more specific delivery systems for the administration of anti-tumoral agents. In this sense, the efficacy of conventional therapies used for cancer treatment, such as chemotherapy, immune checkpoint inhibitors and radiation therapy, are often limited by their lack of specificity and their potential to cause adverse secondary effects on healthy tissues. Therefore, designing specific cell-targeted delivery systems for anti-tumoral agents presents a promising approach to overcoming the limitations of conventional cancer therapies. In this review we summarize the advances in the use of nanoparticles for Specific CellTarget Delivery of anti-tumoral agents from in vitro to clinical studies.

关键词： Nanoparticles Cancer Treatment Trials

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Cannabidiol effects in stem cells: A systematic review

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BIOFACTORS 2025年第1期51卷 e2148页

作者： Mesas, Cristina Moreno, Javier Doello, Kevin Pena, Mercedes Lopez-Romero, Juan M. Prados, Jose Melguizo, Consolacion Univ Granada Inst Biopathol & Regenerat Med IBIMER Ctr Biomed Res CIBM Granada Spain Inst Invest Biosanitaria Granada Ibs GRANADA Granada 18012 Spain Virgen Nieves Hosp Serv Med Oncol Granada Spain Univ Malaga Fac Sci Dept Organ Chem Malaga Spain Univ Granada Fac Med Dept Anat & Embryol Granada 18071 Spain

Stem cells play a critical role in human tissue regeneration and repair. In addition, cancer stem cells (CSCs), subpopulations of cancer cells sharing similar characteristics as normal stem cells, are responsible for tumor metastasis and resistance to chemo- and radiotherapy and to tumor relapse. Interestingly, all stem cells have cannabinoid receptors, such as cannabidiol (CBD), that perform biological functions. The aim of this systematic review was to analyze the effect of CBD on both somatic stem cells (SSCs) and CSCs. Of the 276 articles analyzed, 38 were selected according to the inclusion and exclusion criteria. A total of 27 studied the effect of CBD on SSCs, finding that 44% focused on CBD differentiation effect and 56% on its protective activity. On the other hand, 11 articles looked at the effect of CBD on CSCs, including glioblastoma (64%), lung cancer (27%), and breast cancer (only one article). Our results showed that CBD exerted a differentiating and protective effect on SCCs. In addition, this molecule demonstrated an antiproliferative effect on some CSCs, although most of the analyses were performed in vitro. Therefore, although in vivo studies should be necessary to justify its clinical use, CBD and its receptors could be a specific target to act on both SSCs and CSCs.

关键词： stem cellscancer stem cells CBD in vitro in vivo

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The quality and reporting of recommendation documents to enhance the integrity of clinical trials: A systematic review and critical appraisal

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MEDICINA DE FAMILIA-SEMERGEN 2025年第2期51卷 102333页

作者： Butt, F. A. Nunez-Nunez, M. Juhasz, B. Bueno-Cavanillas, A. Khan, K. S. Univ Granada Dept Prevent Med & Publ Hlth Granada Spain Biosanit Res Inst Granada Ibs GRANADA Granada Spain Consortium Biomed Res Epidemiol & Publ Hlth CIBERE Madrid Spain Semmelweis Univ Dept Family Med Budapest Hungary

Background: Randomised clinical trials (RCTs) hold the highest validity level in effectiveness research. However, there is a growing concern regarding their trustworthiness. We aimed to appraise the quality and reporting of recommendation documents regarding research integrity to describe their contribution towards fostering RCT integrity. Methods: Following prospective registration (https://***/10.17605/***/DN93K), searches of electronic databases (Scopus, PubMed, Google Scholar) and relevant websites were performed from inception to 30 July 2023 without language limitations. Data extraction and document appraisal using adapted versions of AGREE II, RIGHT and ACCORD checklists were carried out in duplicate. Appraisal data were synthesised as % of the maximum score and documents were classified as: good >= 70%, average 50-69%, and poor < 50%. results: From 1310 citations 14 recommendation documents were selected. Of these, 11 documents (78%) were of poor quality according to all three appraisal checklists. Reviewer agreement was 86-100% regarding the checklist items. The top three documents were: " International multi-stakeholder consensus statement on clinical trial integrity"(score 70% on AGREE II, 96% on RIGHT and 88% on ACCORD);" Development of consensus on essential virtues for ethics and research integrity"(score 51% on AGREE II, 71% on RIGHT and 77% on ACCORD);and " Hong Kong principles for assessing researchers"(score 19% on AGREE II, 57% on RIGHT and 10% on ACCORD). Conclusion There is a room from improvement in the quality and reporting of recommendation documents to help fostering RCT integrity. All stakeholders in the RCT lifecycle making concerted efforts to improve trust in evidence-based medicine need robust guidance to underpin research integrity policies and guidelines.

关键词： Recommendation document Clinical trial research integrity

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