Unveiling the neuroprotective properties of isoflavones: current evidence, molecular mechanisms and future perspectives.

Neurodegenerative diseases encompass a wide range of debilitating and incurable brain disorders characterized by the progressive deterioration of the nervous system's structure and function. Isoflavones, which are naturally occurring polyphenolic phytochemicals, have been found to regulate various cellular signaling pathways associated with the nervous system. The main objective of this comprehensive review is to explore the neuroprotective effects of isoflavones, elucidate the underlying mechanisms, and assess their potential for treating neurodegenerative disorders. Relevant data regarding isoflavones and their impact on neurodegenerative diseases were gathered from multiple library databases and electronic sources, including PubMed, Google Scholar, Web of Science, and Science Direct. Numerous isoflavones, including genistein, daidzein, biochanin A, and formononetin, have exhibited potent neuroprotective properties against various neurodegenerative diseases. These compounds have been found to modulate neurotransmitters, which in turn contributes to their ability to protect against neurodegeneration. Both in vitro and in vivo experimental studies have provided evidence of their neuroprotection mechanisms, which involve interactions with estrogenic receptors, antioxidant effects, anti-inflammatory properties, anti-apoptotic activity, and modulation of neural plasticity. This review aims to provide current insights into the neuroprotective characteristics of isoflavones and shed light on their potential therapeutic applications in future clinical scenarios.

Exploring the role of LIAS-related cuproptosis in systemic lupus erythematosus.

BACKGROUND: Cuproptosis is a novel mode of cell death, which is strongly related to energy metabolism in mitochondria and regulated by protein lipoylation. Currently, the molecular mechanisms of cuproptosis-related genes (CRGs) involved in systemic lupus erythematosus (SLE) largely remained unclear, our study is aimed to explore the mechanisms of cuproptosis and CRGs involved in SLE. METHODS: Bulk RNA-seq datasets were collected to display the expressions of CRGs in peripheral blood mononuclear cells (PBMCs) of SLE and healthy individuals, and then ROC analysis was used to establish the diagnostic models of CRGs. Next, the immune infiltration analyses were applied to reveal the difference of immune cells infiltration in LIAS-low and LIAS-high group. Additionally, WGCNA analysis was performed to find the gene modules significantly correlated with the LIAS expression level. We also performed the functional enrichment analyses for LIAS-related gene modules to determine the potential pathways involved in the development of SLE. Finally, scRNA-seq dataset was used to cluster immune cell subsets, reveal the activated pathways, and study cell-cell interactions in LIAS-low and LIAS-high cells. RESULT: We found CDKN2A was significantly increased and LIAS was significantly decreased in SLE patients compared with healthy individuals. The AUC score showed that LIAS had a great diagnostic value than other CRGs. Additionally, the results of immune infiltration analyses showed that immune cells proportion were diverse in LIAS-low and LIAS-high samples. The gene sets related to LIAS expression level were involved in dephosphorylation of JAK1 by SHP1, phosphorylation of STAT2, cytokine signaling in immune system, expression of interferon-alpha and beta, inhibition of JAK kinase activity by SOCS1/3, and so on. Finally, the results of cell-cell communication showed that CCL- (CCL5 + CCR1) and ANNEXIN- (ANXA1 + FPR1) might play an essential role in the communication network between LIAS-low and LIAS-high cells. CONCLUSION: Above findings inferred that LIAS-mediated cuproptosis might involve in a comprehensive cellular and molecular mechanism to cause the occurrence and development of SLE.

Danggui Buxue Tang potentiates the cytotoxicity of 5-fluorouracil on colorectal adenocarcinoma cells: A signaling mediated by c-Jun N-terminal kinase.

Danggui Buxue Tang (DBT) is a well-known Chinese herbal recipe often prescribed in clinical treatment for menopausal and cardiovascular symptoms. 5-Fluorouracil (5-FU) is a chemotherapy drug that treats several cancers; however, it causes severe adverse effects and multidrug resistance. Combining natural medications can reduce the side effects of 5-FU use. Hence, we aimed to determine the role of DBT in strengthening the anticancer capabilities of 5-FU in a cultured colorectal adenocarcinoma cell line (HT-29 cell) and xenograft nude mice. HT-29 cells cultured with DBT did not exhibit cytotoxicity. However, co-administration of DBT with 5-FU significantly increased apoptosis and the expression of apoptotic markers. The inhibition of proliferation induced by DBT and 5-FU was shown to be mediated by c-Jun N-terminal kinase signaling. In addition, the potentiation effect of 5-FU and DBT was demonstrated in reducing tumor size, expressions of Ki67 and CD34 in HT-29 xenograft mice. This finding suggests that DBT can work with 5-FU as a novel chemotherapeutic strategy for treating colon cancer.

Effects and mechanisms of dietary bioactive compounds on breast cancer prevention.

Breast cancer (BC) is the most often diagnosed cancer among females globally and has become an increasing global health issue over the last decades. Despite the substantial improvement in screening methods for initial diagnosis, effective therapy remains lacking. Still, there has been high recurrence and disease progression after treatment of surgery, endocrine therapy, chemotherapy, and radiotherapy. Considering this view, there is a crucial requirement to develop safe, freely accessible, and effective anticancer therapy for BC. The dietary bioactive compounds as auspicious anticancer agents have been recognized to be active and their implications in the treatment of BC with negligible side effects. Hence, this review focused on various dietary bioactive compounds as potential therapeutic agents in the prevention and treatment of BC with the mechanisms of action. Bioactive compounds have chemo-preventive properties as they inhibit the proliferation of cancer cells, downregulate the expression of estrogen receptors, and cell cycle arrest by inducing apoptotic settings in tumor cells. Therapeutic drugs or natural compounds generally incorporate engineered nanoparticles with ideal sizes, shapes, and enhance their solubility, circulatory half-life, and biodistribution. All data of in vitro, in vivo, and clinical studies of dietary bioactive compounds and their impact on BC were collected from Science Direct, PubMed, and Google Scholar. The data of chemopreventive and anticancer activity of dietary bioactive compounds were collected and orchestrated in a suitable place in the review. These shreds of data will be extremely beneficial to recognize a series of additional diet-derived bioactive compounds to treat BC with the lowest side effects.

Broad-spectrum antiviral activity of Spatholobus suberectus Dunn against SARS-CoV-2, SARS-CoV-1, H5N1, and other enveloped viruses.

The current COVID-19 pandemic caused by SARS-Cov-2 is responsible for more than 6 million deaths globally. The development of broad-spectrum and cost-effective antivirals is urgently needed. Medicinal plants are renowned as a complementary approach in which antiviral natural products have been established as safe and effective drugs. Here, we report that the percolation extract of Spatholobus suberectus Dunn (SSP) is a broad-spectrum viral entry inhibitor against SARS-CoV-1/2 and other enveloped viruses. The viral inhibitory activities of the SSP were evaluated by using pseudotyped SARS-CoV-1 and 2, HIV-1ADA and HXB2 , and H5N1. SSP effectively inhibited viral entry and with EC50 values ranging from 3.6 to 5.1 µg/ml. Pre-treatment of pseudovirus or target cells with SSP showed consistent inhibitory activities with the respective EC50 value of 2.3 or 2.1 µg/ml. SSP blocked both SARS-CoV-2 spike glycoprotein and the host ACE2 receptor. In vivo studies indicated that there was no abnormal toxicity and behavior in long-term SSP treatment. Based on these findings, we concluded that SSP has the potential to be developed as a drug candidate for preventing and treating COVID-19 and other emerging enveloped viruses.

In-Silico Drug Toxicity and Interaction Prediction for Plant Complexes Based on Virtual Screening and Text Mining.

Potential drug toxicities and drug interactions of redundant compounds of plant complexes may cause unexpected clinical responses or even severe adverse events. On the other hand, super-additivity of drug interactions between natural products and synthetic drugs may be utilized to gain better performance in disease management. Although without enough datasets for prediction model training, based on the SwissSimilarity and PubChem platforms, for the first time, a feasible workflow of prediction of both toxicity and drug interaction of plant complexes was built in this study. The optimal similarity score threshold for toxicity prediction of this system is 0.6171, based on an analysis of 20 different herbal medicines. From the PubChem database, 31 different sections of toxicity information such as "Acute Effects", "NIOSH Toxicity Data", "Interactions", "Hepatotoxicity", "Carcinogenicity", "Symptoms", and "Human Toxicity Values" sections have been retrieved, with dozens of active compounds predicted to exert potential toxicities. In Spatholobus suberectus Dunn (SSD), there are 9 out of 24 active compounds predicted to play synergistic effects on cancer management with various drugs or factors. The synergism between SSD, luteolin and docetaxel in the management of triple-negative breast cancer was proved by the combination index assay, synergy score detection assay, and xenograft model.

New Insights into Dietary Pterostilbene: Sources, Metabolism, and Health Promotion Effects.

Pterostilbene (PTS), a compound most abundantly found in blueberries, is a natural analog of resveratrol. Several plant species, such as peanuts and grapes, produce PTS. While resveratrol has been extensively studied for its antioxidant properties, recent evidence also points out the diverse therapeutic potential of PTS. Several studies have identified the robust pharmacodynamic features of PTS, including better intestinal absorption and elevated hepatic stability than resveratrol. Indeed, due to its higher bioavailability paired with reduced toxicity compared to other stilbenes, PTS has become an attractive drug candidate for the treatment of several disease conditions, including diabetes, cancer, cardiovascular disease, neurodegenerative disorders, and aging. This review article provides an extensive summary of the nutraceutical potential of PTS in various disease conditions while discussing the crucial mechanistic pathways implicated. In particular, we share insights from our studies about the Nrf2-mediated effect of PTS in diabetes and associated complications. Moreover, we elucidate the important sources of PTS and discuss in detail its pharmacokinetics and the range of formulations and routes of administration used across experimental studies and human clinical trials. Furthermore, this review also summarizes the strategies successfully used to improve dietary availability and the bio-accessibility of PTS.

Crosstalk between Depression and Breast Cancer via Hepatic Epoxide Metabolism: A Central Comorbidity Mechanism.

Breast cancer (BC) is a serious global challenge, and depression is one of the risk factors and comorbidities of BC. Recently, the research on the comorbidity of BC and depression has focused on the dysfunction of the hypothalamic-pituitary-adrenal axis and the persistent stimulation of the inflammatory response. However, the further mechanisms for comorbidity remain unclear. Epoxide metabolism has been shown to have a regulatory function in the comorbid mechanism with scattered reports. Hence, this article reviews the role of epoxide metabolism in depression and BC. The comprehensive review discloses the imbalance in epoxide metabolism and its downstream effect shared by BC and depression, including overexpression of inflammation, upregulation of toxic diols, and disturbed lipid metabolism. These downstream effects are mainly involved in the construction of the breast malignancy microenvironment through liver regulation. This finding provides new clues on the mechanism of BC and depression comorbidity, suggesting in particular a potential relationship between the liver and BC, and provides potential evidence of comorbidity for subsequent studies on the pathological mechanism.

Characterization of acute pain-induced behavioral passivity in mice: Insights from statistical modeling.

Affective-motivational disturbances are highly inconsistent in animal pain models. The reproducibility of the open-field test in assessing anxiety, malaise or disability remains controversial despite its popularity. While traumatic, persistent or multiregional pain models are commonly considered more effective in inducing negative affect or functional impairment, the early psychobehavioral changes before pain chronification are often underexplored. Here, we aimed to clarify the fundamental relationship between hypernociception and passive distress-like behavior using a model of transient inflammatory pain. To minimize latent confounders and increase data consistency, male C57BL/6N mice were habituated to the open-field arena 6 times before receiving the unilateral intraplantar injection of prostaglandin E2 (PGE2) or vehicle. Open-field (40-min exploration) and nociceptive behavior were evaluated repeatedly along the course of hypernociception in both wild-type and transgenic mice with a known pronociceptive phenotype. To reduce subjectivity, multivariate open-field behavioral outcomes were analyzed by statistical modeling based on exploratory factor analyses, which yielded a 2-factor solution. Within 3 hr after PGE2 injection, mice developed significantly reduced center exploration (factor 1) and a marginally significant increase in their habituation tendency (factor 2), which were not apparent in vehicle-injected mice. The behavioral passivity generally improved as hypernociception subsided. Therefore, transient inflammatory irritation is sufficient to suppress mouse open-field exploratory activity. The apparent absence of late affective-motivational changes in some rodents with prolonged hypernociception may not imply a lack of preceding or underlying neuropsychological alterations. Procedural pain after invasive animal experiments, however small, should be assessed and adequately controlled as a potential research confounder.

Diet-Derived Phytochemicals Targeting Colon Cancer Stem Cells and Microbiota in Colorectal Cancer.

Colorectal cancer (CRC) is a fatal disease caused by the uncontrolled propagation and endurance of atypical colon cells. A person's lifestyle and eating pattern have significant impacts on the CRC in a positive and/or negative way. Diet-derived phytochemicals modulate the microbiome as well as targeting colon cancer stem cells (CSCs) that are found to offer significant protective effects against CRC, which were organized in an appropriate spot on the paper. All information on dietary phytochemicals, gut microbiome, CSCs, and their influence on CRC were accessed from the various databases and electronic search engines. The effectiveness of CRC can be reduced using various dietary phytochemicals or modulating microbiome that reduces or inverses the progression of a tumor as well as CSCs, which could be a promising and efficient way to reduce the burden of CRC. Phytochemicals with modulation of gut microbiome continue to be auspicious investigations in CRC through noticeable anti-tumorigenic effects and goals to CSCs, which provides new openings for cancer inhibition and treatment.

Impact of consumption of repeatedly heated cooking oils on the incidence of various cancers- A critical review.

Repeated heating of vegetable oils at high temperatures during cooking is a very common cooking practice. Repeatedly heated cooking oils (RCO) can generate varieties of compounds, including polycyclic aromatic hydrocarbons (PAH), some of which have been reported as carcinogenic. RCO is one of the commonly consumed cooking and frying medium. These RCO consumption and inhalation of cooking fumes can pose a serious health hazard. Taking into account exploratory study, the present review aims to provide the consumption of RCO and its fumes cause the high incidence of genotoxic, mutagenic, tumorogenic and various cancers. The information on RCO and its fumes were collected through a library database and electronic search (ScienceDirect, PubMed, and Google Scholar). Remarkable studies demonstrated that the health adverse effects of RCO and its cooking fumes have been often attributed to their detrimental properties and ease to genotoxic, mutagenic and carcinogenic activities. RCO and its cooking fumes were found to enhance the incidence of aberrant cells, including breaks, fragments, exchanges and multiple chromosomal damages and micronuclei in a dose-dependent manner. Furthermore, the large consumption of RCO has been associated with a number of malignancies, including lung, colorectal, breast, and prostate cancers. The present review provides additional insights into the polluting features of PAHs produced various cancers via cooking activities in indoor environments.

Anti-Diabetic Effects and Mechanisms of Dietary Polysaccharides.

Diabetes mellitus is a multifactorial, heterogeneous metabolic disorder, causing various health complications and economic issues, which apparently impacts the human's life. Currently, commercial diabetic drugs are clinically managed for diabetic treatment that has definite side effects. Dietary polysaccharides mainly derive from natural sources, including medicinal plants, grains, fruits, vegetables, edible mushroom, and medicinal foods, and possess anti-diabetic potential. Hence, this review summarizes the effects of dietary polysaccharides on diabetes and underlying molecular mechanisms related to inflammatory factors, oxidative stress, and diabetes in various animal models. The analysis of literature and appropriate data on anti-diabetic polysaccharide from electronic databases was conducted. In vivo and in vitro trials have revealed that treatment of these polysaccharides has hypoglycemic, hypolipidemic, antioxidant, and anti-inflammatory effects, which enhance pancreatic ß-cell mass and alleviates ß-cell dysfunction. It enhances insulin signaling pathways through insulin receptors and activates the PI3K/Akt pathway, and eventually modulates ERK/JNK/MAPK pathway. In conclusion, dietary polysaccharides can effectively ameliorate hyperglycemia, hyperlipidemia, low-grade inflammation, and oxidative stress in type 2 diabetes mellitus (T2DM), and, thus, consumption of polysaccharides can be a valuable choice for diabetic control.

A critical review on hepatoprotective effects of bioactive food components.

BACKGROUND: Bioactive food components are nonessential biomolecules, which help to give beneficial effects to human being against several diseases. Natural bioactive food components derived from plants and animals, such as phytosterols, carotenoids, polyphenols and fatty acids, have been proposed as valuable substitutions for anticipation and management of hepatotoxic effects and its chronic complications based on in vitro and in vivo studies. OBJECTIVES OF THE STUDY: To summarize drugs and chemical-induced hepatotoxicity and review how various bioactive food components attenuate the hepatotoxicity via cellular mechanisms. RESULTS: Remarkable studies demonstrated that the health promoting effects of bioactive components originated from plants have been frequently attributed to their antioxidant properties and facilitate to increase cellular antioxidant defense system and thereby scavenge free radicals, inhibit lipid peroxidation, augment anti-inflammatory potential, and further protect the liver from damage. CONCLUSION: In this critical review, we summarize current progress in clarifying the molecular mechanism in hepatotoxicity and curative potential of the bioactive food components and its successive clinical outcomes in the field of drug discovery and overcome the problems of medication and chemical-induced hepatotoxic effects.

Causal Relationship between Diet-Induced Gut Microbiota Changes and Diabetes: A Novel Strategy to Transplant Faecalibacterium prausnitzii in Preventing Diabetes.

The incidence of metabolic disorders, including diabetes, has elevated exponentially during the last decades and enhanced the risk of a variety of complications, such as diabetes and cardiovascular diseases. In the present review, we have highlighted the new insights on the complex relationships between diet-induced modulation of gut microbiota and metabolic disorders, including diabetes. Literature from various library databases and electronic searches (ScienceDirect, PubMed, and Google Scholar) were randomly collected. There exists a complex relationship between diet and gut microbiota, which alters the energy balance, health impacts, and autoimmunity, further causes inflammation and metabolic dysfunction, including diabetes. Faecalibacterium prausnitzii is a butyrate-producing bacterium, which plays a vital role in diabetes. Transplantation of F. prausnitzii has been used as an intervention strategy to treat dysbiosis of the gut's microbial community that is linked to the inflammation, which precedes autoimmune disease and diabetes. The review focuses on literature that highlights the benefits of the microbiota especially, the abundant of F. prausnitzii in protecting the gut microbiota pattern and its therapeutic potential against inflammation and diabetes.

Anti-Obesity Effects of Medicinal and Edible Mushrooms.

Obesity is a group of metabolic disorders caused by multiple factors, including heredity, diet, lifestyle, societal determinants, environment, and infectious agents, which can all lead to the enhancement of storage body fat. Excess visceral fat mass in adipose tissue generate several metabolic disorders, including cardiovascular diseases with chronic inflammation based pathophysiology. The objective of the current review is to summarize the cellular mechanisms of obesity that attenuate by antioxidant potentials of medicinal and edible mushrooms. Studies have showed that mushrooms potentially have antioxidant capacities, which increase the antioxidant defense systems in cells. They boost anti-inflammatory actions and thereby protect against obesity-related hypertension and dyslipidemia. The practice of regular consumption of mushrooms is effective in the treatment of metabolic syndrome, including obesity, and thus could be a good candidate for use in future pharmaceutical or nutraceutical applications.

Telomerase Inhibitors from Natural Products and Their Anticancer Potential.

Telomeres and telomerase are nowadays exploring traits on targets for anticancer therapy. Telomerase is a unique reverse transcriptase enzyme, considered as a primary factor in almost all cancer cells, which is mainly responsible to regulate the telomere length. Hence, telomerase ensures the indefinite cell proliferation during malignancy-a hallmark of cancer-and this distinctive feature has provided telomerase as the preferred target for drug development in cancer therapy. Deactivation of telomerase and telomere destabilization by natural products provides an opening to succeed new targets for cancer therapy. This review aims to provide a fundamental knowledge for research on telomere, working regulation of telomerase and its various binding proteins to inhibit the telomere/telomerase complex. In addition, the review summarizes the inhibitors of the enzyme catalytic subunit and RNA component, natural products that target telomeres, and suppression of transcriptional and post-transcriptional levels. This extensive understanding of telomerase biology will provide indispensable information for enhancing the efficiency of rational anti-cancer drug design.

Polyphenol-Rich Dry Common Beans (Phaseolus vulgaris L.) and Their Health Benefits.

Polyphenols are plant metabolites with potent anti-oxidant properties, which help to reduce the effects of oxidative stress-induced dreaded diseases. The evidence demonstrated that dietary polyphenols are of emerging increasing scientific interest due to their role in the prevention of degenerative diseases in humans. Possible health beneficial effects of polyphenols are based on the human consumption and their bioavailability. Common beans (Phaseolus vulgaris L.) are a greater source of polyphenolic compounds with numerous health promoting properties. Polyphenol-rich dry common beans have potential effects on human health, and possess anti-oxidant, anti-diabetic, anti-obesity, anti-inflammatory and anti-mutagenic and anti-carcinogenic properties. Based on the studies, the current comprehensive review aims to provide up-to-date information on the nutritional compositions and health-promoting effect of polyphenol-rich common beans, which help to explore their therapeutic values for future clinical studies. Investigation of common beans and their impacts on human health were obtained from various library databases and electronic searches (Science Direct PubMed, and Google Scholar).

Polyphenol-Rich Lentils and Their Health Promoting Effects.

Polyphenols are a group of plant metabolites with potent antioxidant properties, which protect against various chronic diseases induced by oxidative stress. Evidence showed that dietary polyphenols have emerged as one of the prominent scientific interests due to their role in the prevention of degenerative diseases in humans. Possible health beneficial effects of polyphenols are measured based on the human consumption and their bioavailability. Lentil (Lens culinaris; Family: Fabaceae) is a great source of polyphenol compounds with various health-promoting properties. Polyphenol-rich lentils have a potential effect on human health, possessing properties such as antioxidant, antidiabetic, anti-obesity, anti-hyperlipidemic, anti-inflammatory and anticancer. Based on the explorative study, the current comprehensive review aims to give up-to-date information on nutritive compositions, bioactive compounds and the health-promoting effect of polyphenol-rich lentils, which explores their therapeutic values for future clinical studies. All data of in vitro, in vivo and clinical studies of lentils and their impact on human health were collected from a library database and electronic search (Science Direct, PubMed and Google Scholar). Health-promoting information was gathered and orchestrated in the suitable place in the review.

Spin-orbit interaction in a two-dimensional hole gas at the surface of hydrogenated diamond.

Hydrogenated diamond possesses a unique surface conductivity as a result of transfer doping by surface acceptors. Yet, despite being extensively studied for the past two decades, little is known about the system at low temperature, particularly whether a two-dimensional hole gas forms at the diamond surface. Here we report that (100) diamond, when functionalized with hydrogen, supports a p-type spin-3/2 two-dimensional surface conductivity with a spin-orbit interaction of 9.74 ± 0.1 meV through the observation of weak antilocalization effects in magneto-conductivity measurements at low temperature. Fits to 2D localization theory yield a spin relaxation length of 30 ± 1 nm and a spin-relaxation time of ∼ 0.67 ± 0.02 ps. The existence of a 2D system with spin orbit coupling at the surface of a wide band gap insulating material has great potential for future applications in ferromagnet-semiconductor and superconductor-semiconductor devices.

Ankle arthroscopy to manage sequelae after ankle fractures.

PURPOSE: The role of ankle arthroscopy in managing the consequences of ankle fractures is yet to be fully established. This study aims to assess this procedure in terms of the accuracy of preoperative diagnosis, re-operation rate and patient-reported outcomes. METHODS: Sixty-six patients were identified [mean age 40 years (SD 13 years)] who had undergone ankle arthroscopy following a fracture of the distal tibia or fibula. Medical case notes were reviewed to ascertain details of the index injury, intra-operative findings and identify any further procedures. Patients were then contacted using a standardized questionnaire to assess satisfaction and return to normal function. RESULTS: Injury occurred in a mean of 2 years 10 months before arthroscopy (SD 13 months, min 6 months). Forty-nine of 66 fractures (74 %) had been managed operatively. The commonest indication for arthroscopy was anterior impingement (45 %) followed by degenerative change (30 %) and osteochondral lesions (OCL) (18 %). Intra-operative findings revealed an unexpected OCL or frank degenerative change in 20 % of patients. Using a Kaplan-Meier estimate 1 year after arthroscopy, 10 % of patients had undergone further surgery. This had increased to 34 % by 4 years after arthroscopy. Four patients underwent ankle fusion. Questionnaires were completed by 55/66 patients (84 %). Only 28 patients (50 %) felt surgery allowed them to return to normal activity. Thirty-nine patients reported a benefit from surgery (75 %) whilst 43 were satisfied (77 %) and 48 (86 %) would recommend the procedure to a friend. CONCLUSIONS: Intra-articular pathology was significantly underestimated preoperatively for one patient in five. Arthroscopy improved symptoms in 75 % of patients who complain of ankle symptoms after fracture of the ankle or distal tibia. However, further procedures were required in 34 % of patients. The findings of this study help guide patient counselling and operative decision-making in this challenging group of patients. LEVEL OF EVIDENCE: IV.