Pathogenesis Of Ulcer Research Articles

Design, synthesis, in vitro urease inhibitory potentials and in silico molecular docking study of benzimidazole bearing thiosemicarbazides/sulfonamide Analogues

The nickel-containing urease enzyme is responsible for the pathogenesis of hepatic coma, hepatic encephalopathy, urolithiasis, gastric and peptic ulcer. These enzymes also have a negative effect on the efficacy of soil nitrogen to produce crops. The urease enzyme inhibitors may be thought as a strategy for reducing the negative effects of ureolytic bacteria. The present study involves a novel approach to the synthesis benzimidazole thiosemicarbazides and sulphonamide derivatives as potent urease inhibitor. All the analogues exhibited good inhibition potential. Among the thiosemicarbazides series, the most potent were analogs 1 g and 1 h having an IC50 = 2.40 ± 0.10 and 3.10 ± 0.10 µM respectively. Among the sulphonamide series, the most potent analogs were 2f and 2j having an IC50 = 3.90 ± 0.10 and 1.40 ± 0.001 µM respectively. Structure activity relationship study shows that among the two series, the most potent analogs were those having electron-withdrawing groups. Molecular docking study was carried out to check the interactions between the synthesized compounds and the urease enzyme's active sites. Furthermore, to evaluate the stability of the most active compound in complex with the urease enzyme a total of 200 ns MD simulation was carried out. The MD simulation study revealed that the compound formed a more stable complex with the urease enzyme and remained stable throughout the 200 ns MD simulation. All Compounds were verified for cytotoxicity against 3T3 mouse fibroblast cell line and detected nontoxic.

The role of programmed cell death in diabetic foot ulcers.

Diabetic foot ulcer, is a chronic complication afflicting individuals with diabetes, continue to increase worldwide, immensely burdening society. Programmed cell death, which includes apoptosis, autophagy, ferroptosis, necroptosis and pyroptosis, has been increasingly implicated in the pathogenesis of diabetic foot ulcer. This review is based on an exhaustive examination of the literature on 'programmed cell death' and 'diabetic foot ulcers' via PubMed. The findings revealed that natural bioactive compounds, noncoding RNAsand certain proteins play crucial roles in the healing of diabetic foot ulcers through various forms of programmed cell death, including apoptosis, autophagy, ferroptosis and pyroptosis.

Triazolothiadiazoles and Triazolothiadiazines as New and Potent Urease Inhibitors: Insights from In Vitro Assay, Kinetics Data, and In Silico Assessment.

Hyperactivity of the urease enzyme induces the pathogenesis of peptic ulcers and gastritis. The identification of new urease inhibitors can reduce the activity of urease. Therefore, in the current study, we have evaluated 28 analogues of triazolothiadiazole and triazolothiadiazine heteroaromatics for their in vitro urease inhibitory efficacy. All the tested compounds displayed a remarkable inhibitory potential ranging from 3.33 to 46.83 μM. Among them, compounds 5k and 5e emerged as lead inhibitors with IC50 values of 3.33 ± 0.11 and 3.51 ± 0.49 μM, respectively. The potent inhibitory potential of these compounds was ∼6.5-fold higher than that of the marketed drug thiourea (IC50 = 22.45 ± 0.30 μM). The mechanistic insights from kinetics experiments of the highest potent inhibitors (4g, 5e, and 5k) revealed a competitive type of inhibition with ki values 2.25 ± 0.0028, 3.11 ± 0.0031, and 3.62 ± 0.0034 μM, respectively. In silico modeling was performed to investigate the binding interactions of potent inhibitors with the enzyme active site residues, which strongly supported our experimental results. Furthermore, ADME analysis also showed good druglikeness properties demonstrating the potential of these compounds to be developed as lead antiurease agents.

Design, synthesis, and biological studies of the new cysteine-N-arylacetamide derivatives as a potent urease inhibitor.

Inhibition of Helicobacter pylori urease is an effective method in the treatment of several gastrointestinal diseases in humans. This bacterium plays an important role in the pathogenesis of gastritis and peptic ulceration. Considering the presence of cysteine and N-arylacetamide derivatives in potent urease inhibitors, here, we designed hybrid derivatives of these pharmacophores. Therefore, cysteine-N-arylacetamide derivatives 5a-l were synthesized through simple nucleophilic reactions with good yield. In vitro urease inhibitory activity assay of these compounds demonstrated that all newly synthesized compounds exhibited high inhibitory activity (IC50 values = 0.35-5.83 μM) when compared with standard drugs (thiourea: IC50 = 21.1 ± 0.11 μM and hydroxyurea: IC50 = 100.0 ± 0.01 μM). Representatively, compound 5e with IC50 = 0.35 μM was 60 times more potent than strong urease inhibitor thiourea. Enzyme kinetic study of this compound revealed that compound 5e is a competitive urease inhibitor. Moreover, a docking study of compound 5e was performed to explore crucial interactions at the urease active site. This study revealed that compound 5e is capable to inhibit urease by interactions with two crucial residues at the active site: Ni and CME592. Furthermore, a molecular dynamics study confirmed the stability of the 5e-urease complex and Ni chelating properties of this compound. It should be considered that, in the following study, the focus was placed on jack bean urease instead of H. pylori urease, and this was acknowledged as a limitation.

Examination of Feet in People with Diabetes

Diabetic foot is a common complication of diabetes and leads to considerable morbidity and mortality. Neuropathy, deformity, infection and ischemia play a key role in the pathogenesis of diabetic foot ulcer. A multidisciplinary team approach by a nurse, physician, diabetic foot surgeon and the caregiver as well as close monitoring can prevent foot complications. Proper foot care, foot hygiene, annual foot examination and correct choice of footwear are main factors in preventing foot problems, ulceration and amputations. Physicians play a lead role in early detection and prevention of foot problems. This article will focus on how to perform foot examination in routine clinical practice.

Mapping cellular senescence networks in human diabetic foot ulcers.

Cellular senescence, a cell fate defined by irreversible cell cycle arrest, has been observed to contribute to chronic age-related conditions including non-healing wounds, such as diabetic foot ulcers. However, the role of cellular senescence in the pathogenesis of diabetic foot ulcers remains unclear. To examine the contribution of senescent phenotypes to these chronic wounds, differential gene and network analyses were performed on publicly available bulk RNA sequencing of whole skin biopsies of wound edge diabetic foot ulcers and uninvolved diabetic foot skin. Wald tests with Benjamini-Hochberg correction were used to evaluate differential gene expression. Results showed that cellular senescence markers, CDKN1A, CXCL8, IGFBP2, IL1A, MMP10, SERPINE1, and TGFA, were upregulated, while TP53 was downregulated in diabetic foot ulcers compared to uninvolved diabetic foot skin. NetDecoder was then used to identify and compare context-specific protein-protein interaction networks using known cellular senescence markers as pathway sources. The diabetic foot ulcer protein-protein interaction network demonstrated significant perturbations with decreased inhibitory interactions and increased senescence markers compared to uninvolved diabetic foot skin. Indeed, TP53 (p53) and CDKN1A (p21) appeared to be key regulators in diabetic foot ulcer formation. These findings suggest that cellular senescence is an important mediator of diabetic foot ulcer pathogenesis.

Integrating GWAS and proteome data to identify novel drug targets for MU

Mouth ulcers have been associated with numerous loci in genome wide association studies (GWAS). Nonetheless, it remains unclear what mechanisms are involved in the pathogenesis of mouth ulcers at these loci, as well as what the most effective ulcer drugs are. Thus, we aimed to screen hub genes responsible for mouth ulcer pathogenesis. We conducted an imputed/in-silico proteome-wide association study to discover candidate genes that impact the development of mouth ulcers and affect the expression and concentration of associated proteins in the bloodstream. The integrative analysis revealed that 35 genes play a significant role in the development of mouth ulcers, both in terms of their protein and transcriptional levels. Following this analysis, the researchers identified 6 key genes, namely BTN3A3, IL12B, BPI, FAM213A, PLXNB2, and IL22RA2, which were related to the onset of mouth ulcers. By combining with multidimensional data, six genes were found to correlate with mouth ulcer pathogenesis, which can be useful for further biological and therapeutic research.

Deep Learning-Based Classification and Feature Extraction for Predicting Pathogenesis of Foot Ulcers in Patients with Diabetes.

The World Health Organization (WHO) has identified that diabetes mellitus (DM) is one of the most prevalent disease worldwide. Individuals with DM have a higher risk of mortality, and it is crucial to prioritize the treatment of foot ulcers, which is a significant complication associated with the disease, as they lead to the development of plantar ulcers, which results in the need to amputate part of the foot or leg. People with diabetes are at risk of experiencing various complications, such as heart disease, eye problems, kidney dysfunction, nerve damage, skin issues, foot ulcers, and dental diseases. Unawareness of the risk associated with diabetic foot ulcers (DFU) is a significant contributing factor to the mortality of diabetic patients. Evolving technological advancements such as deep learning techniques can be used to predict the symptoms of diabetic foot ulcers as early as possible, which helps to provide effective treatment to DM patients. This research introduces a methodology for analyzing images of foot ulcers in diabetic patients, focusing on feature extraction and classification. The dataset used in this study was collected from historical medical records and foot images of patients with diabetes, who commonly experience foot ulcers as a major complication. The dataset was pre-processed and segmented, and features were extracted using a deep recurrent neural network (DRNN). Image and numerical/text data were extracted separately, and the normal and abnormal diabetes ranges were identified. Foot images of patients with abnormal diabetes ranges were separated and classified using a pre-trained fast convolutional neural network (PFCNN) with U++net. The classification procedure involves the analysis of foot ulcers to predict their pathogenesis. To assess the effectiveness of the proposed technique, the study presented simulation results, including a confusion matrix and receiver operating characteristic curve. These results specifically focused on predicting two classes: normal and abnormal diabetes foot ulcerations. The analysis yielded various parameters, including accuracy, precision, recall curve, and area under the curve. The main goal of the study was to introduce an novel technique for assessing the risk of foot ulceration development in patients with diabetes, leveraging the analysis of foot ulcer images. The researchers collected a dataset of foot images and medical data from historical records of patients with diabetes and pre-processed and segmented the data. They then used a deep recurrent neural network to extract features from the segmented data and identified normal and abnormal diabetes ranges based on numerical and text data. Foot images of patients with abnormal diabetes ranges were classified using a pre-trained fast convolutional neural network with U++net to examine foot ulcers and forecast the development of the risk of diabetic foot ulcers (DFU). The study assessed the accuracy of the proposed technique as 99.32% by simulating results for feature extraction and the classification of diabetic foot ulcers. A comparison was made between this proposed technique and existing approaches.

Andrographis paniculata as Promising Novel Protective Therapy of Oxidative Stress in Indomethacin-Induced Gastric Ulcer in Rats

This research investigated the effect of Andrographis paniculata (AP) on oxidative stress following indomethacin-induced gastric ulcer in rats. A total of 20 male albino Wistar rats (150-180g) used for this study were grouped into four (n=5): 1, Negative Control; 2, Positive Control and 3, test group treated with normal chow, 20mg/kg indomethacin, 20 mg/kg indomethacin plus omeprazole at 20mg/kg and 20mg/kg indomethacin plus AP at 16.7 mg/kg respectively. After treatment period, estimation of oxidative stress parameters was carried out on the animals. The LD50 of aqueous extract of AP was 50mg/kg bw. Body weight change was significantly reduced in omeprazole treated group compared to all other groups while extract treated group had significantly increased body weight change. There was a significant increase in malondialdehyde (MDA) level of ulcer untreated group compared to other groups. The two treated groups had significantly reduced MDA compared to ulcer untreated group. There was a significant decrease in the levels of GPx and SOD of ulcer untreated group compared to control. Meanwhile, these were significantly increased in extract and omeprazole treated groups compared to ulcer untreated group. Catalase was significantly increased in all three groups when compared to control but its level was significantly increased in extract treated group compared to ulcer untreated and omeprazole treated groups. From this study, AP has proved to protect against oxidative stress implicated in the pathogenesis of ulcer. If this result is applicable to humans, further research and use of AP in ameliorating debilitating consequences of peptic ulcer should be encouraged.

The first 5 years of Helicobacter pylori research-With an emphasis on the United Kingdom.

In the 1970s, 1% of the UK population consulted with dyspepsia; fiberoptic gastroscopy allowed biopsy specimens under direct vision enabling systematic histopathology. Steer et al described clusters of flagellated bacteria closely apposed to the gastric epithelium associated with chronic active gastritis. The first UK series of Helicobacter pylori following Marshall's 1983 visit to Worcester confirmed the association of H. pylori with gastritis. UK researchers completed much early helicobacter research as there were many UK campylobacteriologists. Steer and Newell proved the Campylobacter-like organisms grown on culture were the same as those seen in the gastric mucosa using antiserum raised by inoculating rabbits with H. pylori from cultures. Wyatt, Rathbone, and others showed a strong correlation between the number of organisms, type and severity of acute gastritis, immunological response, and bacterial adhesion similar to enteropathogenic E coli. Seroprevalence studies indicated H. pylori increased with age. Histopathologists also showed peptic duodenitis was in effect "gastritis in the duodenum" caused by H. pylori, unifying its role in the pathogenesis of both gastritis and duodenal ulceration. These bacteria were initially called Campylobacter pyloridis and then C. pylori. However, electron microscopy suggested that the bacteria were not campylobacters, and this was supported by differences in fatty acid and polyacrylamide electrophoresis profiles. In-vitro tests indicated that H. pylori was susceptible to penicillins, erythromycin, and quinolones, but not trimethoprim or cefsulodin allowing development of selective media for culture. Monotherapy with erythromycin ethylsuccinate was ineffective, and patients treated with bismuth subsalicylate initially responded with clearance of H. pylori and the associated gastritis, but then many relapsed. Thus, pharmacokinetic and treatment studies were important to direct suitable dual and triple treatments. Work optimized serology, and the rapid biopsy urease and urea breath tests. The link between H.pylori and gastric cancer was established in large seroprevalence studies, and H. pylori test and treat for dyspepsia became routine.

Histopathologic Study of Gastritis and Helicobacter Pylori Infection at a Tertiary Centre in Kathmandu

Introduction: Chronic gastritis is a chronic inflammation of the gastric mucosa characterized by infiltration of the superficial mucosa by chronic inflammatory cells and with progressive spread to involve the whole mucosa leading to atrophy and intestinal metaplasia and may even progress to the development of carcinoma. Chronic infection with Helicobacter pylori (H. Pylori) is believed to be the major causative agent in the pathogenesis of chronic active gastritis, duodenal and gastric ulcer along with gastric carcinoma. Sydney system classifies gastritis by the intensity of mononuclear inflammatory infiltrates, activity of polymorphs, atrophy, metaplasia and dysplasia and presence of H. pylori.
 Methods: Observational, descriptive, cross-sectional retrospective study conducted at Department of Pathology, Kathmandu Model Hospital, Kathmandu, Nepal from January 2015 to December 2015. Record of computerized histopathology reports of all cases of endoscopic gastric biopsies were retrieved from the laboratory. The biopsy samples obtained from both body and antrum were included in the study. The grades of mononuclear cells infiltration, neutrophilic activity, metaplasia, dysplasia and glandular atrophy were determined using the Sydney system classification. The presence or absence of H. pylori was noted in the slides stained with Giemsa stain. Data analysis was done using a Microsoft Excel file.
 Results: Of 128 samples studied, the most common endoscopic findings were erythematous lesions and mononuclear infiltrate was seen in all cases. 61.7% showed moderate inflammation. The activity was seen in 35.9% of cases. H. pylori organism was noted in 48.4% of cases.
 Conclusion: The severity of chronic inflammation and neutrophilic activity are significantly associated with infection by this microorganism.

Molecular evidence for stress, inflammation and structural changes in non-specific ulcers in skin of farmed Chinook salmon (Oncorhynchus tshawytscha)

Fish skin is critical to physical defence against pathogens and there is a need to understand the physiological processes impacting ulcers and their healing. Ulcers have been reported in farmed Chinook salmon in New Zealand. This study investigated stress, immune and structural gene expression in farmed Chinook salmon skin with and without ulcers from two sites in New Zealand sampled from February (higher temperature, late summer) to May (lower temperature, late autumn). Skin samples taken adjacent to non-specific ulcers in May and control fish in February demonstrated upregulation of heat shock protein 70 relative to control fish in May. Anterior gradient 2 expression was upregulated in fish with ulcers relative to control fish (both February and May), suggesting increased mucous cell activity. Based on the results of this study, fish with non-specific ulcers showed evidence of stress, inflammation, re-epithelisation, and delayed healing near the ulcer site, elucidating the importance of these processes in the pathogenesis of non-specific ulcers in farmed chinook salmon.

Addressing the Inertia: A Holistic Approach to Diabetic Foot Evaluation.

Diabetic foot is a well-known complication with considerable morbidity and mortality related to the diabetic population. Neuropathy, deformity, infection and ischemia are important contributors to the pathogenesis of diabetic foot ulcers. A multidisciplinary team approach by physicians, nursing staff, diabetic educators and the caregiver as well as close monitoring of feet by the patient himself can prevent foot-related complications. Proper foot care, foot hygiene, annual foot examination and the correct choice of footwear are the main elements in preventing foot problems like deformity, ulceration and amputations. Physicians play a key role in the early detection and prevention of foot problems. Foot evaluation is the most neglected part of physical examination in diabetic patients. This inertia is evident in both physicians and patients. Emphasis on visual inspection and physical foot examination at every visit may address the morbidity and mortality due to diabetic neuropathy and vasculopathy. This article will highlight extensively history taking and foot examination in the diabetic foot clinic. Optimal glycemic control, simple foot care practices, knowledge and appropriate footwear use play an important role to reduce the disease burden.

Management of Patients With Kennedy Terminal Ulcer: Challenges and Best Practices

Whether receiving acute, long-term, or home care, patients at the end of life may experience skin failure due to hemodynamic changes and insufficient perfusion of skin tissue. Skin failure begins as superficial ulcers that can quickly become full-thickness lesions, which are referred to as Kennedy terminal ulcers. Skin lesions commonly occur in the final 6 weeks of life and can occur even in the presence of a comprehensive care plan. The pathogenesis of Kennedy terminal ulcers is often misunderstood and these ulcers are commonly misdiagnosed as pressure injuries. This confusion may lead to aggressive care with subpar clinical outcomes that cause further psychological and emotional distress to patients and family members. Patients at the end of life must be provided care focused on their comfort rather than wound healing. To provide the highest quality of care to patients, four end-of-life strategies should be used, including: taking account of the preferences of patients and families, protecting the skin, describing the wound, and preserving a high quality of care. The terms, pathophysiological and clinical manifestations, and nursing treatments related to skin failure at the end of life described in the literature are introduced in this paper. Furthermore, monitoring indicators of nursing quality are provided.

Synthesis and biological evaluation of 2-nitrocinnamaldehyde derived thiosemicarbazones as urease inhibitors

Hyperactivity of urease enzyme induces pathogenesis of peptic ulcers and gastritis. The excess of urease can be reduced by introducing various inhibitors. The risk of high urease content also partakes in agriculture field where it declines the environmental health. This alarming situation leads to the mandatory quest of such novel scaffolds that must work wonders in the field of medicinal chemistry. Consequently, we herein report a novel series of N4-substitution of cinnamaldehyde with thiosemicarbazones 3a-q as potential candidates for urease inhibition. These new N4-substituted thiosemicarbazones 3a-q of indistinct chemical scaffolds were characterized by advanced spectroscopic techniques, such as ESI-MS, 13CNMR, 1HNMR, and FTIR. All newly synthesized compounds showed significant urease inhibitions with IC50 values in range of 11.4 ± 0.23 to 80.6 ± 0.52 μM. Furthermore, kinetic studies of compound 3o displayed competitive type of inhibition with ki value 8.65 ± 0.37 µM. For analysis of structure‒activity relationship and interactions pattern of all compounds, molecular docking was used, which revealed excellent binding interactions of compounds with the active site residues, such as nickel atom coordination, π–cation, π–π interactions, and hydrogen bonding. Additionally, the predicted pharmacokinetics and drug-likeness of compounds suggest that these compounds have good pharmacokinetic and physicochemical properties, and these compounds follow rules of drug-likeness.

The Correlation Between IFNG Gene Methylation and Th1|Th2 Cell Balance in ROU and the Interventional Study of Jiaweidaochi Powder.

The pathogenesis of recurrent oral ulcers (ROU) is complex, with a long duration of illness and challenging to cure. According to traditional Chinese medicine (TCM),"heat accumulation in the heart-spleen" is one of the main causative factors. Jiaweidaochi powder (JWDCP) is based on the ancient Chinese medicine formula JWDCS, with the addition of Tongcao and gypsum and the removal of Mu Tong. It is generally used to treat "heat accumulation in the heart-spleen." Previous studies have demonstrated that it effectively reduces recurrence rates and is anti-inflammatory in modulating immunity. The ROU rats' model for JWDCP intervention treatment had been established, and histological tests revealed that JWDCP has a therapeutic effect on the pathological changes in the oral mucosa. In addition, the methylation levels of peripheral blood IFNG gene were detected by bisulfite sequencing PCR (BSP), and the methylation levels of the IFNG promoter region in the model group and each dose group were lower than those in the control group. However, no significant methylation differences were observed. Furthermore, the results of enzyme-linked immunosorbent assay (ELISA) and RNA quantitative polymerase chain reaction showed that JWDCP could reduce IFN-γ and IL-4 protein concentrations, with high GATA-3 mRNA production, T-bet mRNAproduction was upgraded,elevated IL-4 mRNA levels, and reduced IFN-γ mRNAlevels after treatment (P < 0.001). The expression of transcription factor T-betmRNA and GATA-3 gene mRNA was accompanied by changes in IFN-γmRNA and IL-4mRNA, demonstrating that Th2 type differentiation in RAS suppresses the body's immunity and that the imbalance of transcription factor expression further leads to Th1/Th2 drift. JWDCP is likely to reduce the protein concentration by regulating the imbalance of transcription factors and enhancing antioxidant capacity, thus achieving therapeutic effects. Treatment of recurrent oral ulcer models is not sufficient to reset IFNG methylation levels, correlating with the refractoriness of ROU, further confirming the complexity of epigenetic mechanisms and that epigenetic alterations in specific mediators may persist locally.

New approach to pathogenesis and treatment of trophycal ulcers

Introduction. Trophic ulcers are one of the most common medical ailments worldwide. Treatment of patients with trophic ulcers is difficult not only because they often recur, but also because they are difficult to treat. Purpose. Study the clinical features and present our own results of combined methods of treatment of trophic ulcers of venous etiology. Materials and methods. The study involved 100 patients with trophic ulcers of the lower extremities of venous, diabetic and atherosclerotic etiology, who had a history and were treated for varicose veins of the lower extremities and post-thrombotic disease. Examination of patients included questionnaires, clarification of complaints, anamnesis data, causes of development, examination and ultrasound diagnostics (duplex examination). The examination of the ulcer included determining the location, size, appearance, base of the wound, the level of exudation and assessment of the condition of the skin around the defect. Results. The etiological factors in the development of trophic ulcers were: varicose disease with chronic venous insufficiency – 25 patients, post-thrombotic disease – 55 patients. All patients underwent only conservative treatment of trophic venous ulcers with the appointment of a placenta compositum. After the treatment of a group of patients, out of 100 patients with venous trophic ulcers, 89% were cured within 4 months, 8% were cured within 2 years, and in 3 % ulcers did not heal for more than two years. The average duration of the course of ulcers was 12 months. The average size of trophic ulcers based on the results of the analysis was 8 cm2. Complete healing of venous ulcers was most often observed in the age group 61–73 years in 30% patients. Conclusion. The use of the compositum placenta contributed to the acceleration of wound healing, which made it possible to obtain more effective results.

Factors Associated with Leg Ulcers in Adults with Sickle Cell Disease in Brazil.

To define the prevalence of leg ulcers and identify the clinical and laboratory factors associated with leg ulcers in adult participants. The authors conducted a cross-sectional study of 1,109 patients who were 18 years or older with SS or Sβ0-thalassemia genotypes from a Brazilian cohort. Investigators assessed the prevalence of factors associated with leg ulcers from 2013 to 2017. The prevalence of leg ulcers was 21%. Increasing age (odds ratio [OR], 1.07; range, 1.06-1.09), male sex (OR, 2.03; range, 1.44-2.87), treatment with chronic transfusion therapy (OR, 1.88; range, 1.15-3.03), higher indirect bilirubin levels (OR, 1.48; range, 1.02-2.16), and low hemoglobin levels (OR, 2.17; range, 1.52-3.11) were associated with leg ulcers. Participants who self-reported as Black (OR, 6.75; range, 2.63-21.32), mixed (OR, 3.91; range, 1.55-12.20), and other/unknown (OR, 3.84; range, 1.04-15.24) were more likely to have leg ulcers compared with those who self-reported as White. The prevalence of leg ulcers in this Brazilian cohort was higher than the prevalence reported in developed countries. Known factors such as age and male sex were corroborated. The increased bilirubin level and decreased hemoglobin levels among participants with leg ulcers support the hypothesis that hemolysis is correlated with leg ulcer pathogenesis. Self-reported black skin color was an independent predictor of leg ulcers and warrants further study to understand the etiology and implications of this finding.

Urease and Carbonic Anhydrase Inhibitory Effect of Xanthones from Aspergillus nidulans, an Endophytic Fungus of Nyctanthes arbor-tristis.

Urease plays a major role in the pathogenesis of peptic and gastric ulcer and also causes acute pyelonephritis and development of infection-induced reactive arthritis. Carbonic anhydrases (CA) cause pathological disorders such as epilepsy (CA I), glaucoma, gastritis, renal, pancreatic carcinomas, and malignant brain tumors (CA II). Although various synthetic urease and carbonic anhydrase inhibitors are known, these have many side effects. Hence, present studies were undertaken on ethyl acetate extract of Aspergillus nidulans, an endophytic fungus separated from the leaves of Nyctanthes arbor-tristis Linn.and led to the isolation of five furanoxanthones, sterigmatin (1: ), sterigmatocystin (3: ), dihydrosterigmatocystin (4: ), oxisterigmatocystin C (5: ), acyl-hemiacetal sterigmatocystin (6: ), and a pyranoxanthone (2: ). Acetylation of 3: gave compound O-acetyl sterigmatocystin (7: ). Their chemical structures were elucidated by 1H and 13C NMR and MS. The inhibitory effect of isolated compounds was evaluated on urease and carbonic anhydrase (bCA II) enzymes in vitro. Compounds 3: and 6: showed significant urease inhibition (IC50 19and 21 µM), while other compounds exhibited varying degrees of urease inhibition (IC50 33 - 51 µM). Compounds 4, 6: and 7: exhibited significant inhibition of bCA II (IC50 values 21, 25 and 18 µM respectively), compounds 1: -3: displayed moderate inhibition (IC50 61, 76 and 31 µM respectively) while 5: showed no inhibition. A mechanistic study of the most active urease inhibitors was also performed using enzyme kinetics and molecular docking. All compounds were found non-toxic on the NIH-3T3 cell line.

LncRNA SNHG16 Knockdown Promotes Diabetic Foot Ulcer Wound Healing via Sponging MiR-31-5p.

Diabetic foot ulcers are caused by nerve abnormalities and vascular lesions in the distal lower limbs of diabetic patients. However, the causes of diabetic foot ulcers are diverse and the treatment process is complex. Therefore, understanding the pathogenesis of diabetic foot ulcers through lncRNA and formulating effective means are the key to the cure of patients. Tissues were collected from 76 diabetic foot ulcer patients and 50 non-diabetic patients undergoing traumatic amputation. Human dermal fibroblasts (HDFs) were induced by high glucose to obtain diabetic foot ulcer cell model. The lncRNA SNHG16 (SNHG16) and miR-31-5p expression in tissues and cells was detected by real-time quantitative reverse transcription PCR (RT-qPCR). Cell Counting Kit-8 (CCK-8) and Transwell assays were used to evaluate the biological behavior of the cells, and the association between SNHG16 and miR-31-5p was explored by luciferase reporting assay. SNHG16 was distinctly expressed in diabetic foot ulcer tissue samples, while miR-31-5p was decreased. In vitro cell function assays confirmed that the proliferation level was inhibited in the constructed diabetic foot ulcer cell model (HG group), as was the migration and invasion ability. After transfection with silencing SNHG16, the biological behavior of the cells was promoted. Mechanistically, SNHG16 sponge miR-31-5p regulated disease progression. Recovery experiments revealed that miR-31-5p inhibitor counteracted the effect of silencing SNHG16 on cell viability. SNHG16 knockdown may regulate the biological function of cells by targeting miR-31-5p to promote wound healing and ameliorate the condition of diabetic foot ulcer patients.