Biochemical Abnormalities Research Articles

Effect of pomegranate peel with/without autologous bone marrow on healing of acute cutaneous wounds in alloxan-induced diabetic rabbits.

Healing of bum wounds is commonly associated with many complications. Every year various new repair materials are developed and experimentally used for treating burn wounds. Humans with diabetes mellitus usually suffer from chronic wound healing. Vascular, neuropathic, immune function, and biochemical abnormalities each contribute to the altered tissue repair. One underlying factor that accompanies all diabetic ulcerations is poor vascular flow, a circumstance that impedes proper wound healing. Numerous studies have highlighted the importance of adequate vascular sufficiency and vessel proliferation in tissue repair and the lack thereof in diabetic wound healing. Other studies have looked at whether disarrayed capillary remodeling and maturation of vessels might play a role in impaired diabetic wound healing. This investigation has been planned to report the influence of treatment with a mixture of both the powder of pomegranate peel (PP) accompanied with an autologous bone marrow (BM) on the cure of burn injuries in experimentally induced diabetic rabbits. Alloxan monohydrate has been applied to create diabetes in 50 rabbits. Then in each rabbit, two deep second-degree burn wounds were experimentally created. The animals were then divided randomly into 5 treatment sections: non-treatment controls (C1), treated with an available commercial powder for wound (C2), treatment with powder of PP, treatment with alone BM, and the final group treated with PP powder with bone marrow (PPBM). The speed of wound closure and the histopathological changes during healing were measured. The levels of the biomarkers of rabbit platelet-derived growth factor AA (PDGF-AA) and rabbit protease-activated receptor 1 (PAR-1) were measured on days 0, 4, 8, and 12. Wound healing was markedly more rapid in all the treatment groups versus the control non-treated group. Interestingly, a rapid wound cure was significantly observed in the PPBM group versus the other treatment ones. The histological assessment clarified a significant elevation in the fibroblast and collagen scores in the PPBM group versus the other sections. In addition, there were significant increases in the serum levels of the biomarkers PDGF-AA and PAR-1 among groups. Dependent on the results of current research, it can be concluded that both PP powder with BM PPBM significantly accelerate the healing process of burn wounds in experimentally induced diabetic rabbits.

Clinical Features and Risk Factors for Drug-Induced Liver Injury: A Retrospective Study From China

PurposeWith the prolongation of human life expectancy and the outbreak of COVID-19, antineoplastic agents, anti-infective drugs, and cardiovascular system drugs have been widely applied, resulting in a growing incidence of drug-induced liver injury (DILI) year by year. This study aimed to investigate signals, clinical characteristics, and risk factors in patients with liver injury. MethodsA retrospective analysis was conducted on inpatients clinically diagnosed with DILI from 2019 to 2021 in one tertiary hospital in mainland China. The hepatic biochemical indices, clinical manifestations and suspected drugs of the patients were counted. We determined causality assessed by the Roussel Uclaf Causality Assessment Method in patients that the biochemistry met the diagnostic criteria recommended by the International Serious Adverse Events Consortium and compared them with contemporaneous patients diagnosed as DILI but with hepatic biochemical abnormalities only to identify the injure types and risk factors for DILI. FindingsA total of 1167 patients from 2639 initial participants with DILI were included. According to the injured target cells, it can be divided into hepatocellular injury type 351 cases (30.08%), cholestatic injury type 97 cases (8.31%), mixed injury type 27 cases (2.31%), and biochemical abnormal only type 692 cases (59.30%). It involved 1738 cases of suspected drugs, 349 drugs, and the top 3 drug categories were antineoplastic agents, anti-infectives, and traditional Chinese medicines, with Cyclophosphamide, Atorvastatin, and Liuzasulfapyridine as the top 3 in order of ranking. The main symptoms of patients were darker urine, decreased appetite, and yellow sclera. The overall prognosis of patients with DILI was favorable, with 280 recovered cases (23.99%), 691 improved cases (59.21%), 189 not improved cases (16.20%), and 7 deaths (0.60%). There were significant differences in gender, age, malignancy, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, gamma-glutamyltransferase, albumin, international normalized ratio, and prognosis among patients with different injury types (P < 0.05). Multiple logistic regression analysis showed that female (odds ratio [OR] = 1.897, P < 0.001), alcohol use (OR = 1.905, P = 0.001), malignancy (OR = 0.417, P < 0.001), and pregnancy (OR = 0.201, P = 0.011) were independent factors influencing DILI. ImplicationsFor most patients with liver injury, the manifestations are mild elevation of liver biochemistry without other symptoms (biochemical abnormal only type). The rest of the patients are predominantly of the hepatocellular injury type. Female and alcohol abuse patients are the risk factors of DILI, reminding clinicians to strengthen education on safe drug use, give individualized treatment, and regularly monitor liver function indexes in the patients.

#1725 Co-relation of bone mineral density (BMD) with static bone histomorphometric parameters in haemodialysis patients

Abstract Background and Aims A mineral bone disorder of CKD (CKD MBD) is a complication with abnormal bone turnover, mineralization, volume, vascular calcification, and a spectrum of biochemical abnormalities. This clinical study was designed to determine the correlation between BMD (DEXA parameter) and static bone histomorphometry in hemodialysis patients. Method This was a cross-sectional study in patients undergoing maintenance hemodialysis aged 18-60 years. Bone biopsy was done from the iliac crest, fixed in alcohol, processed, and stained by RGB trichrome stain. Histomorphometric analysis was done by using NIH software (image J) and Adobe Photoshop software for image masking into black and white for volume calculation. Determination of BMD was performed by DEXA SCAN (Model HORIZON A). The detection sections included the central skeleton's three areas- anteroposterior lumbar (L1-L4) spine, proximal femur (femoral neck), and distal radius. Results A total of 46 patients on maintenance hemodialysis were included. Thirty-one (67.39%) were male, and the mean age was 34.43 ± 12.5 years. Amongst the study population, 60.87% (28) patients had osteopenia, 19.57%(9) patients had osteoporosis, and 19.57%(9) patients had normal BMD. Out of 46, four biopsies were inconclusive, 50% (21) had adynamic bone disease, 19.05%(8) had high turnover bone disease, 19.05%(8) had high mixed uremic osteodystrophy and 11.9%(5) patients had normal parameters. Among biochemical parameters, serum iPTH, ALP, and calcium had a significant association with bone turnover. BMD was significantly associated with age. However, it had no significant association with dialysis vintage, sex, or the type of renal osteodystrophy. Static bone histomorphometric parameters were not significantly associated with the T score. Conclusion PTH, ALP, and serum calcium were significantly associated with bone turnover. Adynamic bone disease was the most common renal osteodystrophy. BMD was not significantly associated with static bone histomorphometric parameters in our study.

Clinical predictive value of the CRP-albumin-lymphocyte index for prognosis of critically ill patients with sepsis in intensive care unit: a retrospective single-center observational study.

Sepsis is a complex syndrome characterized by physiological, pathological, and biochemical abnormalities caused by infection. Its development is influenced by factors such as inflammation, nutrition, and immune status. Therefore, we combined C-reactive protein (CRP), albumin, and lymphocyte, which could reflect above status, to be the CRP-albumin-lymphocyte (CALLY) index, and investigated its association with clinical prognosis of critically ill patients with sepsis. This retrospective observational study enrolled critically ill patients with sepsis who had an initial CRP, albumin, and lymphocyte data on the first day of ICU admission. All data were obtained from the Affiliated Hospital of Jiangsu University. The patients were divided into quartiles (Q1-Q4) based on their CALLY index. The outcomes included 30-/60-day mortality and acute kidney injury (AKI) occurrence. The association between the CALLY index and these clinical outcomes in critically ill patients with sepsis was evaluated using Cox proportional hazards and logistic regression analysis. A total of 1,123 patients (63.0% male) were included in the study. The 30-day and 60-day mortality rates were found to be 28.1 and 33.4%, respectively, while the incidence of AKI was 45.6%. Kaplan-Meier analysis revealed a significant association between higher CALLY index and lower risk of 30-day and 60-day mortality (log-rank p < 0.001). Multivariate Cox proportional hazards analysis indicated that the CALLY index was independently associated with 30-day mortality [HR (95%CI): 0.965 (0.935-0.997); p = 0.030] and 60-day mortality [HR (95%CI): 0.969 (0.941-0.997); p = 0.032]. Additionally, the multivariate logistic regression model showed that the CALLY index served as an independent risk predictor for AKI occurrence [OR (95%CI): 0.982 (0.962-0.998); p = 0.033]. The findings of this study indicated a significant association between the CALLY index and both 30-day and 60-day mortality, as well as the occurrence of AKI, in critically ill patients with sepsis. These findings suggested that the CALLY index may be a valuable tool in identifying sepsis patients who were at high risk for unfavorable outcomes.

Potential Clinical Benefit of Very Long Chain Fatty Acid Supplementation in Spinocerebellar Ataxia Type 34.

Spinocerebellar ataxia type 34 (SCA34) is a dominantly inherited disease that causes late-onset ataxia, in association with skin lesions in the form of erythrokeratodermia variabilis. It is caused by mutations in the ELOVL4 gene, which encodes for the ELOVL4 protein and has the function of lengthening very long chain (VLC) fatty acids (FA), which are important components of central myelin. The aim of this work was to review the medical literature on the biochemical abnormalities of SCA34, and based on the obtained information, to propose supplementation of deficient FAs. A review of the ad hoc medical literature was performed. Plasma levels of the ELOVL4 products C32, C34 and C36 FA have not been reported in SCA34 yet. However, pathogenic variants of ELOVL4 revealed deficient biosynthesis of C28, C30, C32, C34 and C36 FA compared to WT in cell cultures, and the levels of ceramides and phosphatidylcholines containing ≥ 34C FA were decreased compared to WT in HeLa cells expressing mutant SCA34 proteins. Besides, a pathological study of SCA34 revealed myelin destruction and loss of oligodendrocytes in cerebral and cerebellar white matter. Levels of VLC-FA should be determined, to identify specifically deficient FAs in SCA34. Cerebellar ataxia could possibly be improved by administration of the deficient FAs, as found in SCA38 with supplementation of docosahexaenoic acid. The authors suggest investigators with access to SCA34, to take into consideration this therapeutic hypothesis, and try to verify the potential efficacy of administration of VLCFA in this disease.

Influence of medical-social and socio-economic factors on infant mortality rate in the Republic of Ingushetia

BACKGROUND: The infant mortality rate, as one of the indicators of the health and quality of life of the population, is an important factor that determines the country’s healthcare priorities. Despite the steadily decreasing infant mortality rates in the Russian Federation, the value of this indicator varies by region; thus, studying the factors influencing its value is relevant. If the leading medical, social, and socioeconomic factors that influence the level of infant mortality could be determined using data from a representative region (Republic of Ingushetia), the main directions for organizing measures aimed at reducing mortality among children in the first year of life will be identified. AIM: To determine the main medical, social and socio-economic factors that influence the infant mortality rate in the Republic of Ingushetia. MATERIALS AND METHODS: An observational single-center retrospective study was performed to examine the influence of medical, social, and socioeconomic factors on the mortality rate of children aged 1 year in the Republic of Ingushetia. The obtained data were compared with similar indicators for the Russian Federation as a whole and the North Caucasus Federal District. RESULTS: During the study period (2011–2019), significant changes were observed in infant mortality rates in the Republic of Ingushetia: infant mortality has decreased because of the age components, leading to the normal ratio of neonatal and post neonatal mortality. Rates of infant mortality from certain conditions arising in the perinatal period, congenital anomalies, and nervous system and circulatory system diseases have significantly decreased. The proportion of women admitted under the supervision of antenatal clinics in the early pregnancy (up to 12 weeks) has increased, the incidence of morbidity among pregnant women has decreased, and the proportion of normal births has been increasing. Although many medical organizations have employed a sufficient number of medical personnel, the coverage for biochemical screening has decreased, detection of malformations and biochemical abnormalities during prenatal diagnostics was low, medical personnel have low qualifications, and the shortage of obstetric and pediatric beds and pathology beds for newborns and premature infants was significant. A statistically significant dependence of the frequency of deaths of children aged 1 year on socioeconomic indicators−unemployment level, monetary income of the population, and housing conditions−was revealed. CONCLUSION: The main medical, social, and socioeconomic factors that influence infant mortality were analyzed using data from the Republic of Ingushetia. Positive and negative trends in the current state of the healthcare system of this republic have been identified.

Lung and Colon Cancer Histopathological Image Classification Using 1D Convolutional Channel-based Attention Networks

Lung and Colon cancer are the leading diseases of death and disability in humans caused by a combination of genetic diseases and biochemical abnormalities. If these are diagnosed in their early stages, they can not be spread in organs and negatively impact human life. Many deep-learning networks have recently been proposed to detect and classify these malignancies. However, incorrect detection or misclassification of these fatal diseases can significantly affect an individual's health and well-being. This paper introduces a novel, cost-effective, and mobile-embedded architecture to diagnose and classify Lung squamous cell carcinomas and adenocarcinomas of the lung and colon from digital pathology images. Extensive experiment shows that our proposed modifications achieve 100% testing results for lung, colon, and lung-and-colon cancer detection. Our novel architecture takes around 0.65 million trainable parameters and around 6.4 million flops to achieve the best lung and colon cancer detection performance. Compared with the other results, our proposed architecture shows state-of-the-art performance.

Partial suppression of BCAA catabolism as a potential therapy for BCKDK deficiency

Branched chain ketoacid dehydrogenase kinase (BCKDK) deficiency is a recently described inherited neurometabolic disorder of branched chain amino acid (BCAA) metabolism implying increased BCAA catabolism. It has been hypothesized that a severe reduction in systemic BCAA levels underlies the disease pathophysiology, and that BCAA supplementation may ameliorate disease phenotypes. To test this hypothesis, we characterized a recent mouse model of BCKDK deficiency and evaluated the efficacy of enteral BCAA supplementation in this model. Surprisingly, BCAA supplementation exacerbated neurodevelopmental deficits and did not correct biochemical abnormalities despite increasing systemic BCAA levels. These data suggest that aberrant flux through the BCAA catabolic pathway, not just BCAA insufficiency, may contribute to disease pathology. In support of this conclusion, genetic re-regulation of BCAA catabolism, through Dbt haploinsufficiency, partially rescued biochemical and behavioral phenotypes in BCKDK deficient mice. Collectively, these data raise into question assumptions widely made about the pathophysiology of BCKDK insufficiency and suggest a novel approach to develop potential therapies for this disease.

Maralixibat in progressive familial intrahepatic cholestasis (MARCH-PFIC): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders, the most prevalent being BSEP deficiency, resulting in disrupted bile formation, cholestasis, and pruritus. Building on a previous phase 2 study, we aimed to evaluate the efficacy and safety of maralixibat-an ileal bile acid transporter inhibitor-in participants with all types of PFIC. MARCH-PFIC was a multicentre, randomised, double-blind, placebo-controlled, phase 3 study conducted in 29 community and hospital centres across 16 countries in Europe, the Americas, and Asia. We recruited participants aged 1-17 years with PFIC with persistent pruritus (>6 months; average of ≥1·5 on morning Itch-Reported Outcome [Observer; ItchRO(Obs)] during the last 4 weeks of screening) and biochemical abnormalities or pathological evidence of progressive liver disease, or both. We defined three analysis cohorts. The BSEP (or primary) cohort included only those with biallelic, non-truncated BSEP deficiency without low or fluctuating serum bile acids or previous biliary surgery. The all-PFIC cohort combined the BSEP cohort with participants with biallelic FIC1, MDR3, TJP2, or MYO5B deficiencies without previous surgery but regardless of bile acids. The full cohort had no exclusions. Participants were randomly assigned (1:1) to receive oral maralixibat (starting dose 142·5 μg/kg, then escalated to 570 μg/kg) or placebo twice daily for 26 weeks. The primary endpoint was the mean change in average morning ItchRO(Obs) severity score between baseline and weeks 15-26 in the BSEP cohort. The key secondary efficacy endpoint was the mean change in total serum bile acids between baseline and the average of weeks 18, 22, and 26 in the BSEP cohort. Efficacy analyses were done in the intention-to-treat population (all those randomly assigned) and safety analyses were done in all participants who received at least one dose of study drug. This completed trial is registered with ClinicalTrials.gov, NCT03905330, and EudraCT, 2019-001211-22. Between July 9, 2019, and March 4, 2022, 125 patients were screened, of whom 93 were randomly assigned to maralixibat (n=47; 14 in the BSEP cohort and 33 in the all-PFIC cohort) or placebo (n=46; 17 in the BSEP cohort and 31 in the all-PFIC cohort), received at least one dose of study drug, and were included in the intention-to-treat and safety populations. The median age was 3·0 years (IQR 2·0-7·0) and 51 (55%) of 93 participants were female and 42 (45%) were male. In the BSEP cohort, least-squares mean change from baseline in morning ItchRO(Obs) was -1·7 (95% CI -2·3 to -1·2) with maralixibat versus -0·6 (-1·1 to -0·1) with placebo, with a significant between-group difference of -1·1 (95% CI -1·8 to -0·3; p=0·0063). Least-squares mean change from baseline in total serum bile acids was -176 μmol/L (95% CI -257 to -94) for maralixibat versus 11 μmol/L (-58 to 80) for placebo, also representing a significant difference of -187 μmol/L (95% CI -293 to -80; p=0·0013). The most common adverse event was diarrhoea (27 [57%] of 47 patients on maralixibat vs nine [20%] of 46 patients on placebo; all mild or moderate and mostly transient). There were five (11%) participants with serious treatment-emergent adverse events in the maralixibat group versus three (7%) in the placebo group. No treatment-related deaths occurred. Maralixibat improved pruritus and predictors of native liver survival in PFIC (eg, serum bile acids). Maralixibat represents a non-surgical, pharmacological option to interrupt the enterohepatic circulation and improve the standard of care in patients with PFIC. Mirum Pharmaceuticals.

The neuroprotective effect of Diosgenin in the rat Valproic acid model of autism

Background and aimAutism spectrum disorder (ASD) is a neurodevelopmental disorder with two core behavioral symptoms restricted/repetitive behavior and social-communication deficit. The unknown etiology of ASD makes it difficult to identify potential treatments. Valproic acid (VPA) is an anticonvulsant drug with teratogenic effects during pregnancy in humans and rodents. Prenatal exposure to VPA induces autism-like behavior in both humans and rodents. This study aimed to investigate the protective effects of Diosgenin in prenatal Valproic acid-induced autism in rats. Methodpregnant Wister female rats were given a single intraperitoneal injection of VPA (600 mg/kg, i.p.) on gestational day 12.5. The male offspring were given oral Dios (40 mg/kg, p.o.) or Carboxymethyl cellulose (5 mg/kg, p.o.) for 30 days starting from postnatal day 23. On postnatal day 52, behavioral tests were done. Additionally, biochemical assessments for oxidative stress markers were carried out on postnatal day 60. Further, histological evaluations were performed on the prefrontal tissue by Nissl staining and Immunohistofluorescence. ResultsThe VPA-exposed rats showed increased anxiety-like behavior in the elevated plus maze (EPM). They also demonstrated repetitive and grooming behaviors in the marble burying test (MBT) and self-grooming test. Social interaction was reduced, and they had difficulty detecting the novel object in the novel object recognition (NOR) test. Also, VPA-treated rats have shown higher levels of oxidative stress malondialdehyde (MDA) and lower GPX, TAC, and superoxide dismutase (SOD) levels. Furthermore, the number of neurons decreased and the ERK signaling pathway upregulated in the prefrontal cortex (PFC). On the other hand, treatment with Dios restored the behavioral consequences, lowered oxidative stress, and death of neurons, and rescued the overly activated ERK1/2 signaling in the prefrontal cortex. ConclusionChronic treatment with Dios restored the behavioral, biochemical, and histological abnormalities caused by prenatal VPA exposure.

Recent advances in fibroblast growth factor 23-related hypophosphatemic disorders.

Fibroblast growth factor 23 (FGF23) is a hormone to reduce blood phosphate concentration. Excessive actions of FGF23 induce FGF23-related hypophosphatemic disorders, such as X-linked hypophosphatemic rickets (XLH) and tumor-induced osteomalacia (TIO). We will summarize recent advances in the diagnosis and treatment of FGF23-related hypophosphatemic disorders. The measurement of blood FGF23 is useful to make a diagnosis of FGF23-related hypophosphatemic disorders. It was reported that many patients with FGF23-related hypophosphatemic disorders, especially TIO, were misdiagnosed, therefore, it is necessary to enhance the awareness of these diseases. A novel method to inhibit excessive actions of FGF23 by a human monoclonal antibody for FGF23, burosumab, has been approved in several countries. In more long-term observation than clinical trials, burosumab has also been shown to improve biochemical abnormalities and symptoms of rickets/osteomalacia. Following these advances, several registries and consensus recommendations on FGF23-related hypophosphatemic disorders, especially XLH, have been established in each country or region. Further long-term effects of burosumab and the precise mechanism of FGF23 overproduction in patients with FGF23-related hypophosphatemic disorders need to be clarified in the future studies.

A retrospective cohort analysis of factors associated with the development of refeeding syndrome in children 0–59 months diagnosed with severe acute malnutrition in a South African setting

BackgroundRefeeding syndrome (RFS) is a life-threatening, underdiagnosed, and under-researched complication in treating children with severe acute malnutrition (SAM). This study aimed to determine the incidence and onset of RFS and identify biochemical abnormalities, clinical signs, and complications associated with RFS development in children, 0–59 months, treated with SAM in a South African public hospital setting. MethodsA retrospective cohort study was performed on hospital medical records of children aged 0–59 months, diagnosed with SAM at Rahima Moosa Mother and Child Hospital, Johannesburg, from 1/10/2014 to 31/12/2018. The onset of RFS among children included in the study was diagnosed based on published criteria for RFS. On admission, children who developed RFS and those who did not were compared concerning biochemistry and clinical signs and symptoms. ResultsA total of 148 medical records were retrieved from the hospital archives. The diagnosis of SAM based on the World Health Organization (WHO) definition was confirmed in 126 children who were then included in the study. The median age of the 126 children (63 % male) with confirmed SAM was 11.2 months (P25:7.0 months; P75:17.0 months). The in-hospital mortality rate was 18.2 %, of which 8.7 % were retrospectively diagnosed as having developed RFS during their recorded hospital stay, despite implementing the WHO treatment guidelines for SAM. A significantly higher percentage of the children who developed RFS presented on admission with hypophosphatemia (p = 0.015), hypokalemia (p = 0.001), hyponatremia (p = 0.001), an international normalized ratio (INR) of above 1.7 (p = 0.025), diarrhea (p = 0.042), dehydration (p = 0.029) and urinary tract infection (UTI) (p = 0.041), than those who did not. Children who developed RFS stayed in hospital significantly longer than those who did not (18 vs. 12 days with a p-value of 0.003). ConclusionIn this population of children with SAM treated in a South African public hospital setting, the presence on hospital admission of low levels of electrolytes, elevated INR, dehydration, diarrhea, and UTI was significantly associated with developing RFS. Recognizing these as possible red flags for developing RFS in children admitted with SAM might contribute to improved outcomes and needs further investigation.

The Protective Effect of Sanggenol L Against DMBA-induced Hamster Buccal Pouch Carcinogenesis Induces Apoptosis and Inhibits Cell Proliferative Signalling Pathway.

Oral squamous cell carcinoma (OSCC) has a poor prognosis when treated with surgery and chemotherapy. Therefore, a new therapy and preventative strategy for OSCC and its underlying mechanisms are desperately needed. The purpose of this study was to examine the chemopreventive effects of sanggenol L on oral squamous cell carcinoma (OSCC). The research focused on molecular signalling pathways in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. The purpose of this study was to look at the biochemical and chemopreventive effects of sanggenol L on 7,12-dimethylbenz(a)anthracene (DMBA)-induced HBP (hamster buccal pouch) carcinogenesis via cell proliferation and the apoptotic pathway. After developing squamous cell carcinoma, oral tumours continued to progress leftward into the pouch 3 times per week for 10 weeks while being exposed to 0.5 % reactive DMBA three times per week. Tumour growth was caused by biochemical abnormalities that induced inflammation, increased cell proliferation, and decreased apoptosis. Oral sanggenol L (10 mg/kg bw) supplementation with cancer-induced model DMBApainted hamsters prevented tumour occurrences, improved biochemistry, inhibited inflammatory markers, decreased cell proliferation marker expression of tumour necrosis factor-alpha (TNF- α), nuclear factor (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and induced apoptosis. Sanggenol L could be developed into a new medicine for the treatment of oral carcinogenesis.

Leaf extracts of Euclea natalensis A.D.C ameliorate biochemical abnormalities in high-fat-low streptozotocin-induced diabetic rats through modulation of the AMPK-GLUT4 pathway

ABSTRACT Euclea natalensis is a commonly used plant in traditional African medicine for treating several diseases, including diabetes. The objective of the present study was to evaluate the antidiabetic effects of the leaf extracts of Euclea natalensis and elucidate some of its mechanisms of action. High-fat diet – low Streptozotocin-induced diabetic Sprague Dawley rats were orally treated with the methanol and dichloromethane extracts (100 and 200 mg/kg bw), and their fasting blood glucose levels, body weights, and food and water intake were measured every seven days for 21 days. Biomarkers of oxidative stress, lipid profile, gluconeogenic enzyme activities, glucose transporter 4 (GLUT 4) protein expression, and AMP-activated protein kinase (AMPK) gene expression were also determined. The 200 mg/kg bw of methanol extracts significantly reduced fasting plasma glucose, glycated hemoglobin (HbAc1), triglycerides, and low-density lipoprotein levels. The extract increased insulin sensitivity and hepatic glycogen synthesis, decreased hepatic glucose output, and increased the activities of antioxidant enzymes in diabetic animals after 21 days of treatment. The methanol extract also significantly upregulated the relative expression of GLUT 4 protein via the promoted expression of skeletal muscle and hepatic AMPK. Histological investigation showed ameliorated pancreatic degeneration and expedited regeneration of islets of Langerhans in diabetic rats treated with the methanol extract compared with the dichloromethane extract. The findings demonstrated that Euclea natalensis has beneficial effects on the biochemical and cell abnormalities of type 2 diabetes, partly via the modulation of the AMPK – GLUT 4 pathway.

Liquiritin Carbomer Gel Cold Paste Promotes Healing of Solar Dermatitis in Mice.

Ultraviolet radiation (UVR) has various effects on human cells and tissues, which can lead to a variety of skin diseases and cause inconvenience to people's lives. Among them, solar dermatitis is one of the important risk factors for malignant melanoma, so prevention and treatment of solar dermatitis is very necessary. Additionally, liquiritin (LQ) has anti-inflammatory effects. In this study, we aimed to evaluate the anti-inflammatory and pro-wound healing effects of liquiritin carbomer gel cold paste (LQ-CG-CP) in vitro and in vivo. The results of MTT experiments showed no cytotoxicity of LQ at concentrations of 40 μg/mL and below and cell damage at UVB irradiation doses above 60 mJ/cm2. Moreover, LQ can promote cell migration. ELISA results also showed that LQ inhibited the elevation of the inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) after UVB irradiation. In the mouse model of solar dermatitis, 2% LQ-CG-CP showed the best therapeutic efficacy for wound healing and relief of itching compared to MEIBAO moist burn moisturizer (MEBO). What is more, the results of skin histopathological examination show that LQ-CG-CP promotes re-epithelialization, shrinks wounds, and promotes collagen production, thus promoting wound healing. Simultaneously, LQ-CG-CP reduced TNF-α, IL-1β, and IL-6 expression. In addition, LQ-CG-CP was not observed to cause histopathological changes and blood biochemical abnormalities in mice. Overall, LQ-CG-CP has great potential for the treatment of solar dermatitis.

Development and validation of the Gastrointestinal Symptom Severity Scale in Spanish children and adolescents.

Functional gastrointestinal disorders (FGIDs) are characterized by chronic or recurrent gastrointestinal symptoms (GS) that are not explained by structural or biochemical abnormalities. FGIDs are related to lower quality of life, increased demands on medical resources, and greater somatization and emotional instability. Furthermore, GS appears to be an indicator of dysbiosis in gut-microbiota, affecting the gut-microbiota-brain relationship. To develop and evaluate the psychometric properties of a new instrument called the Gastrointestinal Symptom Severity Scale (GSSS) using a web-based survey in a sample of neurotypical children and adolescents from Spain. Instrument development and validation processes were applied to the GSSS following its administration as part of an online survey. The sample included 1242 neurotypical children and adolescents. The mean age of participants was 13.95years, with a standard deviation of 1.37years. Overall, 13.8% suffered infectious diarrhea, 12.6% suffered abdominal pain, 5% suffered dyspepsia and 2.6% suffered gastro-esophageal reflux. A single-factor model produced good fit indices. Furthermore, internal consistency and test-retest reliability outcomes were acceptable. The GSSS was found to have acceptable metric measurement invariance. Significant correlations with other instruments were produced and were of expected direction and magnitude, confirming scale validity for hypothesis testing. Conclusions: The GSSS shows promising psychometric properties for assessing GS in neurotypical Spanish adolescents and children. What is Known: • To the best of our knowledge, instruments assessing the severity of gastrointestinal symptoms in children and adolescents are still too few. What is New: • The GSSS shows promising psychometric properties for assessing GS in neurotypical adolescents and children. The GSSS may help improve understanding of GS involvement in the gut-brain microbiota axis in children and adolescents.

Therapeutic Potential of Danyankang Capsule in High-Fat Diet-Induced Cholelithiasis and Its Impact on Liver FXR Signaling and Gut Microbiota.

Cholelithiasis, commonly known as gallstones, represents a prevalent hepatobiliary disorder. This study aimed to elucidate the therapeutic role and mechanism of Danyankang capsulein treating cholelithiasis induced by a high-fat diet in C57BL/6 mice. The therapeutical potential of Danyankang was assessed through biochemical analyses, histopathological examinations, protein detection, and 16S rDNA sequencing. A high-fat diet resulted in cholelithiasis manifestation in mice, with discernable abnormal serum biochemical indices and disrupted biliary cholesterol homeostasis. Danyankang treatment notably ameliorated liver inflammation symptoms and rectified serum and liver biochemical abnormalities. Concurrently, it addressed biliary imbalances. Elevated expressions of toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-κB)/pNF-κB, HMGCR, CYP7A1, and CYP8B1 observed at the inception of cholelithiasis, were notably reduced upon Danyankang administration. Furthermore, 16S rDNA analysis revealed a decline in species number and diversity of the intestinal flora in cholelithiasis-treated mice, while the decline was reversed with Danyankang treatment. Danyankang capsules reduced the abundance of Verrucomicrobiota and increased the abundance of Actinobacteriota and Proteobacteria. In conclusion, the present study demonstrates that Danyankang exerts potent therapeutic efficacy against high-fat diet-induced cholelithiasis. This beneficial outcome is potentially linked to the inhibition of the TLR4/pNF-κB and SHP/CYP7A1/CYP8B1 signaling pathways, as well as the enhancement of intestinal flora species abundance.

Effect of Malaria and Schistosoma mansoni Coinfection on Selected Biochemical Profiles among Patients Attending Selected Health Institutions at Dembiya, Northwest Ethiopia.

Malaria and schistosomiasis are infectious diseases that cause biochemical abnormalities. Malaria and Schistosoma mansoni coinfection causes exacerbations of health consequences and comorbidities. The study area is found in Ethiopia, where coinfection of malaria and S. mansoni is common. However, there is limited data on the biochemical profiles of patients coinfected with malaria and S. mansoni schistosomiasis in the study area. Hence, this study aimed to assess the effect of malaria and S. mansoni schistosomiasis coinfection on selected biochemical profiles. An institutional-based comparative cross-sectional study was conducted from March 30 to August 10, 2022. Using a convenient sampling technique, 70 participants (35 cases and 35 controls) were enrolled in the study. Schistosoma mansoni was detected in stool samples using the wet mount and the Kato Katz method. To detect Plasmodium, both thick and thin blood films were prepared and stained with Giemsa. The blood sample was processed for the analysis of biochemical profiles. All data were analyzed using SPSS version 25. A p value of less than 0.05 was considered statistically significant. The mean values of alanine aminotransferase and aspartate aminotransferase (37.1 U/L and 41.9 U/L, respectively) in coinfected participants were significantly higher than in the healthy control participants (17.4 U/L and 22.0 U/L, respectively) (p < 0.05). Also, the median values of creatinine, total bilirubin, and direct bilirubin (1.51 mg/dL, 2.35 mg/dL, and 0.91 mg/dL, respectively) in coinfected participants were significantly higher than in the healthy control participants (0.85 mg/dL, 0.42 mg/dL, and 0.12 mg/dL, respectively) (p < 0.05). However, median values of total protein (4.82 g/dL) and mean values of glucose (66.6 mg/dL) in coinfected participants were significantly lower than in the healthy control participants (total protein (7.64 g/dL) and glucose (91.9 mg/dL)) (p < 0.05). The results of biochemical profiles in healthy participants were significantly different from those with light, moderate, and heavy S. mansoni infection intensity in malaria and S. mansoni coinfection (p < 0.05). Schistosoma mansoni infection intensity had a positive correlation with biochemical profiles except for total protein and glucose, which correlated negatively in coinfected participants (p > 0.05). Biochemical profiles in coinfection were significantly changed as compared to healthy individuals. As a result, biochemical profile tests should be utilized to monitor and manage coinfection-related problems, as well as to reduce coinfection-related morbidity and death.

Biallelic and monoallelic pathogenic variants in CYP24A1 and SLC34A1 genes cause idiopathic infantile hypercalcemia

ObjectiveIdiopathic infantile hypercalcemia (IIH) is a rare disorder of PTH-independent hypercalcemia. CYP24A1 and SLC34A1 gene mutations cause two forms of hereditary IIH. In this study, the clinical manifestations and molecular aspects of six new Chinese patients were investigated.MethodsThe clinical manifestations and laboratory study of six patients with idiopathic infantile hypercalcemia were analyzed retrospectively.ResultsFive of the patients were diagnosed with hypercalcemia, hypercalciuria, and bilateral medullary nephrocalcinosis. Their clinical symptoms and biochemical abnormalities improved after treatment. One patient presented at age 11 years old with arterial hypertension, hypercalciuria and nephrocalcinosis, but normal serum calcium. Gene analysis showed that two patients had compound heterozygous mutations of CYP24A1, one patient had a monoallelic CYP24A1 variant, and three patients had a monoallelic SLC34A1 variant. Four novel CYP24A1 variants (c.116G > C, c.287T > A, c.476G > A and c.1349T > C) and three novel SLC34A1 variants (c.1322 A > G, c.1697_1698insT and c.1726T > C) were found in these patients.ConclusionsA monoallelic variant of CYP24A1 or SLC34A1 gene contributes to symptomatic hypercalcemia, hypercalciuria and nephrocalcinosis. Manifestations of IIH vary with onset age. Hypercalcemia may not necessarily present after infancy and IIH should be considered in patients with nephrolithiasis either in older children or adults.

Clinical and Biochemical Characteristics of Acute Pancreatitis Patients Attended in a Tertiary Hospital of Bangladesh

Introduction: Acute pancreatitis is a complex, life- threatening disease resulting from acute inflammation of the pancreas which causes considerable morbidity and mortality among the patients. Objectives: To find out the clinical and biochemical characteristics of acute pancreatitis patient attended at the Combined Military Hospital (CMH) Dhaka. Methods: This observational study was conducted at CMH Dhaka among 40 patients of acute pancreatitis admitted from 1st January 2013 to 30th June 2013. Data were collected through face-to-face interview using a pre-tested semi- structured questionnaire and review of the hospital records. Results: Highest number of the respondents (42.5%) belongs to the age group of 20-39 years. The mean age was 44.90 years (±13.46) years and 60.0% of them were male. More than half (57.5%) of the respondents had monthly income in the 20001 to 50000 Taka with average of 31,650(±15,255.60) Taka. All the patients presented with pain in the abdomen which was followed by nausea/ vomiting (82.5%), abdominal distention (72.5%). On examination, it was revealed that all the respondents had abdominal tenderness which was followed by muscle guard (10.0%), ascites (7.5%) and jaundice (5.0%). Almost half (47.50%) of the respondents developed acute pancreatitis due to stone in the gall bladder which was followed by idiopathic origin (30.0%). Eighty five percent of the patients had severe symptoms and rest (15%) had mild symptoms. All the respondents had elevated serum amylase level and 82.5% had elevated serum lipase level. Conclusion: Acute pancreatitis mostly affect young adult male. Most common clinical presentations are upper abdominal pain, nausea/vomiting and abdominal tenderness. Gallstone is the commonest cause of the condition. Serum amylase is the most important biochemical abnormality found in acute pancreatitis. JAFMC Bangladesh. Vol 19, No 1 (June) 2023: 38-41