bluuebunny/crossref_metadata_2025 huggingface dataset:
Vertigoheel promotes rodent cognitive performance in multiple memory tests
Authors: Ott Kerstin , Heikkinen Taneli , Lehtimäki Kimmo K. , Paldanius Kaisa , Puoliväli Jukka , Pussinen Raimo , Andriambeloson Emile , Huyard Bertrand , Wagner Stéphanie , Schnack Cathrin , Wahler Anke , von Einem Bjoern , von Arnim Christine A. F. , Burmeister Yvonne , Weyer Kathrin , Seilheimer Bernd
Published: May 2023

Introduction

Cognitive impairment associated with old age or various brain disorders may be very disabling for affected individuals, placing their carers and public health services under considerable stress. The standard-of-care drugs produce only transient improvement of cognitive impairment in older people, so the search for novel, safe and effective therapeutics that would help to reverse or delay cognitive impairment is warranted. Repurposing pharmacological therapies with well-established safety record for additional indications is a promising recent trend in drug development. Vertigoheel (VH-04), a multicomponent drug made ofAmbra grisea,Anamirta cocculus L.,Conium maculatum, andPetroleum rectificatum, has been successfully used for several decades in the treatment of vertigo. Here, we investigated effects of VH-04 on cognitive performance in standard behavioral tests assessing different types of memory and explored cellular and molecular underpinnings of VH-04’s biological activity.

Methods

In the majority of behavioral experiments, namely in the spontaneous and rewarded alternation tests, passive avoidance test, contextual/cued fear conditioning, and social transmission of food preference, we examined the ability of single and repeated intraperitoneal administrations of VH-04 to improve cognitive parameters of mice and rats disrupted by the application of the muscarinic antagonist scopolamine. In addition, we also assessed how VH-04 affected novel object recognition and influenced performance of aged animals in Morris water maze. Furthermore, we also studied the effects of VH-04 on primary hippocampal neuronsin vitroand mRNA expression of synaptophysin in the hippocampus.

Results

Administration of VH-04 positively influenced visual recognition memory in the novel object recognition test and alleviated the impairments in spatial working memory and olfactory memory caused by the muscarinic antagonist scopolamine in the spontaneous alternation and social transmission of food preference tests. In addition, VH-04 improved retention of the spatial orientation memory of old rats in the Morris water maze. In contrast, VH-04 did not have significant effects on scopolamine-induced impairments in tests of fear-aggravated memory or rewarded alternation. Experimentsin vitroshowed that VH-04 stimulated neurite growth and possibly reversed the age-dependent decrease in hippocampal synaptophysin mRNA expression, which implies that VH-04 may preserve synaptic integrity in the aging brain.

Discussion

Our findings allow a cautious conclusion that in addition to its ability to alleviate manifestations of vertigo, VH-04 may be also used as a cognitive enhancer.
Parent-reported child appetite moderates relationships between child genetic obesity risk and parental feeding practices
Authors: Jansen Elena , Naymik Marcus , Thapaliya Gita , Huentelman Matt , Beauchemin Jennifer , D'Sa Viren , Lewis Candace R. , Deoni Sean ,   RESONANCE consortium, Carnell Susan
Published: May 2023

Background

Food parenting practices are associated with child weight. Such associations may reflect the effects of parents' practices on children's food intake and weight. However, longitudinal, qualitative, and behavioral genetic evidence suggests these associations could, in some cases, reflect parents' response to children's genetic risk for obesity, an instance of gene–environment correlation. We tested for gene–environment correlations across multiple domains of food parenting practices and explored the role of parent-reported child appetite in these relationships.

Materials and methods

Data on relevant variables were available for N = 197 parent–child dyads (7.54 ± 2.67 years; 44.4% girls) participating in RESONANCE, an ongoing pediatric cohort study. Children's body mass index (BMI) polygenic risk score (PRS) were derived based on adult GWAS data. Parents reported on their feeding practices (Comprehensive Feeding Practices Questionnaire) and their child's eating behavior (Child Eating Behavior Questionnaire). Moderation effects of child eating behaviors on associations between child BMI PRS and parental feeding practices were examined, adjusting for relevant covariates.

Results

Of the 12 parental feeding practices, 2 were associated with child BMI PRS, namely, restriction for weight control (β = 0.182, p = 0.011) and teaching about nutrition (β = −0.217, p = 0.003). Moderation analyses demonstrated that when children had high genetic obesity risk and showed moderate/high (vs. low) food responsiveness, parents were more likely to restrict food intake to control weight.

Conclusion

Our results indicate that parents may adjust their feeding practices in response to a child's genetic propensity toward higher or lower bodyweight, and the adoption of food restriction to control weight may depend on parental perceptions of the child's appetite. Research using prospective data on child weight and appetite and food parenting from infancy is needed to further investigate how gene–environment relationships evolve through development.
Integrative analysis of grapevine (Vitis vinifera L) transcriptome reveals regulatory network for Chardonnay quality formation
Authors: Fu Guangqing , Ren Yanhua , Kang Jun , Wang Bo , Zhang Junxiang , Fang Jinggui , Wu Weimin
Published: May 2023

Anthocyanins, total phenols, soluble sugar and fruit shape plays a significant role in determining the distinct fruit quality and customer preference. However, for the majority of fruit species, little is known about the transcriptomics and underlying regulatory networks that control the generation of overall quality during fruit growth and ripening. This study incorporated the quality-related transcriptome data from 6 ecological zones across 3 fruit development and maturity phases of Chardonnay cultivars. With the help of this dataset, we were able to build a complex regulatory network that may be used to identify important structural genes and transcription factors that control the anthocyanins, total phenols, soluble sugars and fruit shape in grapes. Overall, our findings set the groundwork to improve grape quality in addition to offering novel views on quality control during grape development and ripening.
Emotional arousal and valence in patients with fibromyalgia: a pilot study
Authors: Ciuffini Roberta , Cofini Vincenza , Muselli Mario , Necozione Stefano , Piroli Alba , Marrelli Alfonso
Published: May 2023

The pathogenesis of pain in fibromyalgia is still not completely understood. A disrupted emotional modulation could affect the physiology of nociception and contributes to an altered perception of pain. The aim of this study was to test the role of emotional arousal and valence in pain susceptibility in fibromyalgia using the International Affective Picture System (IAPS) paradigm and the Fibromyalgia Severity Scale (FSS). The study focused on comparing emotional arousal and valence between patients with fibromyalgia and the control group. The secondary objective was to examine the correlation between emotional indices and scores on the FSS and the duration of the disease. The 20 patients with fibromyalgia enrolled showed a higher mean arousal score for all the stimuli, including a higher score for unpleasant and socially unpleasant stimuli. The valence scores for social-relevant stimuli were also higher. Increased arousal to unpleasant and socially unpleasant images and increased valence of them correlated with the duration of the disease and the severity of symptoms and could reflect impairment in social cognition and marked sensitivity to pain in interaction with central nociceptive dysregulation.
Core components of a rehabilitation program in pediatric cardiac disease
Authors: Ubeda Tikkanen Ana , Vova Joshua , Holman Lainie , Chrisman Maddie , Clarkson Kristin , Santiago Rachel , Schonberger Lisa , White Kelsey , Badaly Daryaneh , Gauthier Naomi , Pham Tam Dan N. , Britt Jolie J. , Crouter Scott E. , Giangregorio Maeve , Nathan Meena , Akamagwuna Unoma O.
Published: May 2023

There is increasing effort in both the inpatient and outpatient setting to improve care, function, and quality of life for children with congenital heart disease, and to decrease complications. As the mortality rates of surgical procedures for congenital heart disease decrease, improvement in perioperative morbidity and quality of life have become key metrics of quality of care. Quality of life and function in patients with congenital heart disease can be affected by multiple factors: the underlying heart condition, cardiac surgery, complications, and medical treatment. Some of the functional areas affected are motor abilities, exercise capacity, feeding, speech, cognition, and psychosocial adjustment. Rehabilitation interventions aim to enhance and restore functional ability and quality of life for those with physical impairments or disabilities. Interventions such as exercise training have been extensively evaluated in adults with acquired heart disease, and rehabilitation interventions for pediatric patients with congenital heart disease have similar potential to improve perioperative morbidity and quality of life. However, literature regarding the pediatric population is limited. We have gathered a multidisciplinary team of experts from major institutions to create evidence- and practice-based guidelines for pediatric cardiac rehabilitation programs in both inpatient and outpatient settings. To improve the quality of life of pediatric patients with congenital heart disease, we propose the use of individualized multidisciplinary rehabilitation programs that include: medical management; neuropsychology; nursing care; rehabilitation equipment; physical, occupational, speech, and feeding therapies; and exercise training.
Determinants of morbidity and mortality related to health care-associated primary bloodstream infections in neonatal intensive care units: a prospective cohort study from the SEPREVEN trial
Authors: Jaloustre Morgane , Cohen Robert , Biran Valérie , Decobert Fabrice , Layese Richard , Audureau Etienne , Le Saché Nolwenn , Chevallier Marie , Boukhris Mohamed Riadh , Bolot Pascal , Caeymaex Laurence , Tauzin Manon ,   with the SEPREVEN study Group
Published: May 2023

Background

Health care-associated primary bloodstream infections (BSIs), defined as not secondary to an infection at another body site, including central line-associated BSI, are a leading cause of morbidity and mortality in patients in neonatal intensive care units (NICUs). Our objective was to identify factors associated with severe morbidity and mortality after these infections in neonates in NICUs.

Methods

This ancillary study of the SEPREVEN trial included neonates hospitalized ≥2 days in one of 12 French NICUs and with ≥ 1 BSI during the 20-month study period. BSIs (all primary and health care-associated) were diagnosed in infants with symptoms suggestive of infection and classified prospectively as possible (one coagulase-negative staphylococci (CoNS)-growing blood culture) or proven (two same CoNS, or ≥1 recognized pathogen-growing blood culture). BSI consequences were collected prospectively as moderate morbidity (antibiotic treatment alone) or severe morbidity/mortality (life-saving procedure, permanent damage, prolonged hospitalization, and/or death).

Results

Of 557 BSIs identified in 494 patients, CoNS accounted for 378/557 (67.8%) and recognized bacterial or fungal pathogens for 179/557 (32.1%). Severe morbidity/mortality was reported in 148/557 (26.6%) BSIs. Independent factors associated with severe morbidity/mortality were corrected gestational age <28 weeks (CGA) at infection (P < .01), fetal growth restriction (FGR) (P = .04), and proven pathogen-related BSI vs. CoNS-related BSI (P < .01). There were no differences in severe morbidity and mortality between proven and possible CoNS BSIs. In possible BSI, S. epidermidis was associated with a lower risk of severe morbidity than other CoNS (P < .01), notably S. capitis and S. haemolyticus.

Conclusions

In BSIs in the NICU, severe morbidity/mortality was associated with low CGA at infection, FGR, and proven pathogen-related BSIs. When only one blood culture was positive, severe morbidity/mortality were less frequent if it grew with S. epidermidis compared to other CoNS. Further studies to help distinguish real CoNS BSIs from contaminations are needed.

Study registration

ClinicalTrials.gov (NCT02598609).
Critical shortage of capacity to deliver safe paediatric surgery in sub-Saharan Africa: evidence from 67 hospitals in Malawi, Zambia, and Tanzania
Authors: Gajewski Jakub , Pittalis Chiara , Borgstein Eric , Bijlmakers Leon , Mwapasa Gerald , Cheelo Mweene , Juma Adinan , Sardana Muskan , Brugha Ruairi
Published: May 2023

Introduction

Paediatric surgical care is a significant challenge in Sub-Saharan Africa (SSA), where 42% of the population are children. Building paediatric surgical capacity to meet SSA country needs is a priority. This study aimed to assess district hospital paediatric surgical capacity in three countries: Malawi, Tanzania and Zambia (MTZ).

Methods

Data from 67 district-level hospitals in MTZ were collected using a PediPIPES survey tool. Its five components are procedures, personnel, infrastructure, equipment, and supplies. A PediPIPES Index was calculated for each country, and a two-tailed analysis of variance test was used to explore cross-country comparisons.

Results

Similar paediatric surgical capacity index scores and shortages were observed across countries, greater in Malawi and less in Tanzania. Almost all hospitals reported the capacity to perform common minor surgical procedures and less complex resuscitation interventions. Capacity to undertake common abdominal, orthopaedic and urogenital procedures varied—more often reported in Malawi and less often in Tanzania. There were no paediatric or general surgeons or anaesthesiologists at district hospitals. General medical officers with some training to do surgery on children were present (more often in Zambia). Paediatric surgical equipment and supplies were poor in all three countries. Malawi district hospitals had the poorest supply of electricity and water.

Conclusions

With no specialists in district hospitals in MTZ, access to safe paediatric surgery is compromised, aggravated by shortages of infrastructure, equipment and supplies. Significant investments are required to address these shortfalls. SSA countries need to define what procedures are appropriate to national, referral and district hospital levels and ensure that an appropriate paediatric surgical workforce is in place at district hospitals, trained and supervised to undertake these essential surgical procedures so as to meet population needs.
Association of IL-4 and IL-18 genetic polymorphisms with atopic dermatitis in Chinese children
Authors: Shi Jianrong , He Lin , Zheng Huiwen , Li Wei , Huang Shuangshuang , Li Yunling , Tao Ran
Published: May 2023

Background

Atopic dermatitis (AD) is a common chronic inflammatory skin disease, adversely affecting nearly 20% of the pediatric population worldwide. Interleukin-4 (IL-4) and interleukin-18 (IL-18) are considered to be involved in the pathogenesis and development of AD. The aim of this study was to investigate the association of IL-4 and IL-18 gene polymorphisms with the susceptibility and severity of AD in Chinese children.

Methods

Six candidate single nucleotide polymorphisms (SNPs) in IL-4 and IL-18 genes were genotyped through multi-PCR combined with next-generation sequencing in 132 AD children and 100 healthy controls, and all the analyses were performed on blood genome DNA.

Results

The frequencies of G allele, CG genotype and CG + GG genotype of IL-4 rs2243283, as well as the haplotype IL-4/GTT (rs2243283-rs2243250-rs2243248) were all significantly decreased in AD patients compared with the controls [G vs. C: P = 0.033, OR = 0.59; CG vs. CC: P = 0.024, OR = 0.47; CG + GG vs. CC: P = 0.012, OR = 0.49; GTT vs. CCT: P = 0.011, OR = 0.65]. Moreover, the frequencies of A allele, AA genotype and AG + AA genotype of IL-18 rs7106524, along with the haplotype IL-18/CAA (rs187238-rs360718-rs7106524) were statistically increased in the severe AD patients (A vs. G: P < 0.001, OR = 2.79; AA vs. GG: P = 0.003, OR = 5.51; AG + AA vs. GG: P = 0.036, OR = 2.93; CAA vs. CAG: P = 0.001, OR = 2.86).

Conclusions

Our findings suggested that genetic variation in IL-4 rs2243283 such as G allele, CG genotype and CG + GG genotype might confer the reduced susceptibility to AD in Chinese children. Furthermore, A allele, AA genotype and AG + AA genotype of IL-18 rs7106524 explored the strong association with severity in Chinese AD children.
The association between Gabapentin or Pregabalin use and the risk of dementia: an analysis of the National Health Insurance Research Database in Taiwan
Authors: Huang Yu-Hua , Pan Mei-Hung , Yang Hwai-I
Published: May 2023

Objective: Previous studies have shown that gabapentin or pregabalin use is associated with cognitive decline. Herein, we aimed to evaluate the association between gabapentin or pregabalin use and the risk of dementia.

Methods: In this retrospective, population-based matched cohort study, all research data were collected from the 2005 Longitudinal Health Insurance Database, which contains data of 2 million people randomly selected from the National Health Insurance Research Database of Taiwan in 2005. The study extracted data from 1 January 2000, to 31 December 2017. Adult patients taking gabapentin or pregabalin were included in the exposure group, and patients not using gabapentin or pregabalin matched to exposure subjects in a 1:5 ratio by propensity scores composed of age, sex and index date were included in the non-exposure group.

Results: A total of 206,802 patients were enrolled in the study. Of them, 34,467 gabapentin- or pregabalin-exposure and 172,335 non-exposure patients were used for analysis. The mean follow-up day (±standard deviation) after the index date was 1724.76 (±1282.32) and 1881.45 (±1303.69) in the exposure and non-exposure groups, respectively; the incidence rates of dementia were 980.60 and 605.48 per 100,000 person-years, respectively. The multivariate-adjusted hazard ratio of risk of dementia for gabapentin or pregabalin exposure versus the matched non-exposed group was 1.45 (95% confidence interval [CI], 1.36–1.55). The risk of dementia increased with higher cumulative defined daily doses during the follow-up period. Moreover, the stratification analysis revealed that the risk of dementia associated with gabapentin or pregabalin exposure was significant in all age subgroups; however, it was higher in younger patients (age <50) than in the older patients (hazard ratio, 3.16; 95% CI, 2.23–4.47).

Conclusion: Patients treated with gabapentin or pregabalin had an increased risk of dementia. Therefore, these drugs should be used with caution, particularly in susceptible individuals.
Determination of the 95% effective dose of remimazolam tosylate in anesthesia induction inhibits endotracheal intubation response in senile patients
Authors: Qu Liangchao , Liu Mei , Ouyang Ru , Li Tianyuan , Long Dingde , Jiang Yao , Wang Chengyu , Cheng Liqin
Published: May 2023

Background and Purpose: The prevalence of elderly patients prompts anesthesiologists to determine the optimal dose of medication due to the altered pharmacokinetics and pharmacodynamics of this population. The present study aimed to determine the 95% effective dose (ED95) of remimazolam tosylate in anesthesia induction to inhibit endotracheal intubation-related cardiovascular reaction in frail and non-frail senile patients.

Methods: A prospective sequential allocation dose-finding study of remimazolam tosylate was conducted on 80 elderly patients who received general anesthesia between May and June 2022 at the First Affiliated Hospital of Nanchang University. The initial dose was 0.3 mg/kg. The blood pressure and heart rate fluctuations during intubation were either <20% (negative cardiovascular response) or ≥20% (positive cardiovascular response). If positive, the dose of the next patient was increased by 0.02 mg/kg, while if negative, it was reduced by 0.02 mg/kg according to the 95:5 biased coin design (BCD). The ED95 and 95% confidence intervals (CIs) were determined using R-Foundation isotonic regression and bootstrapping methods.

Results: The ED95 of remimazolam tosylate to inhibit the response during tracheal intubation was 0.297 mg/kg (95% CI: 0.231–0.451 mg/kg) and 0.331 mg/kg (95% CI: 0.272–0.472 mg/kg) in frail and non-frail senile patients, respectively.

Conculation and Implications: The CI of the two groups overlap, and no difference was detected in the ED95 of remimazolam tosylate in inhibiting endotracheal intubation-related cardiovascular response in frail and non-frail senile patients. These results suggested that remimazolam tosylate is an optimal anesthesia inducer for all elderly patients.

Clinical Trial Registration:https://www.chictr.org.cn, identifier ChiCTR2200055709.
The construction of a TCM knowledge graph and application of potential knowledge discovery in diabetic kidney disease by integrating diagnosis and treatment guidelines and real-world clinical data
Authors: Zhao Xiaoliang , Wang Yifei , Li Penghui , Xu Julia , Sun Yao , Qiu Moyan , Pang Guoming , Wen Tiancai
Published: May 2023

Background: The complexity and rapid progression of lesions in diabetic kidney disease pose significant challenges for clinical diagnosis and treatment. The advantages of Traditional Chinese Medicine (TCM) in diagnosing and treating this condition have gradually become evident. However, due to the disease’s complexity and the individualized approach to diagnosis and treatment in Traditional Chinese Medicine, Traditional Chinese Medicine guidelines have limitations in guiding the treatment of diabetic kidney disease. Most medical knowledge is currently stored in the process of recording medical records, which hinders the understanding of diseases and the acquisition of diagnostic and treatment knowledge among young doctors. Consequently, there is a lack of sufficient clinical knowledge to support the diagnosis and treatment of diabetic kidney disease in Traditional Chinese Medicine.

Objective: To build a comprehensive knowledge graph for the diagnosis and treatment of diabetic kidney disease in Traditional Chinese Medicine, utilizing clinical guidelines, consensus, and real-world clinical data. On this basis, the knowledge of Traditional Chinese Medicine diagnosis and treatment of diabetic kidney disease was systematically combed and mined.

Methods: Normative guideline data and actual medical records were used to construct a knowledge graph of Traditional Chinese Medicine diagnosis and treatment for diabetic kidney disease and the results obtained by data mining techniques enrich the relational attributes. Neo4j graph database was used for knowledge storage, visual knowledge display, and semantic query. Utilizing multi-dimensional relations with hierarchical weights as the core, a reverse retrieval verification process is conducted to address the critical problems of diagnosis and treatment put forward by experts.

Results: 903 nodes and 1670 relationships were constructed under nine concepts and 20 relationships. Preliminarily a knowledge graph for Traditional Chinese Medicine diagnosis and treatment of diabetic kidney disease was constructed. Based on the multi-dimensional relationships, the diagnosis and treatment questions proposed by experts were validated through multi-hop queries of the graphs. The results were confirmed by experts and showed good outcomes.

Conclusion: This study systematically combed the Traditional Chinese Medicine diagnosis and treatment knowledge of diabetic kidney disease by constructing the knowledge graph. Furthermore, it effectively solved the problem of “knowledge island”. Through visual display and semantic retrieval, the discovery and sharing of diagnosis and treatment knowledge of diabetic kidney disease were realized.
Intraocular pressure effect of intravitreal conbercept injection for retinopathy of prematurity
Authors: Gao Caifeng , Mu Ge , Zhao Huanhuan , Zheng Jiao , Feng Qingyang , Wu Yining , Li Yinan , Huang Xuelin , Sun Wei
Published: May 2023

Purpose: Intravitreal injection of conbercept (IVC) is a novel anti-vascular endothelial growth factor (anti-VEGF) treatment for retinopathy of prematurity (ROP). This study aimed to assess the intraocular pressure (IOP) effect of IVC.

Methods: All IVC surgeries were performed in the Department of Ophthalmology, Guangdong Women and Children Hospital, from January 2021 to May 2021. In this study, 30 eyes of 15 infants who received intravitreal injections of conbercept at a dose of 0.25 mg/0.025 mL were included. The IOP of all participants was measured prior to administering the injection and subsequently at 2 min, 1 h, 1 day, and 1 week thereafter.

Results: We included 30 eyes (10 boys and 5 girls) with ROP. For the male group, the mean birth weight, mean gestational age at birth, and the mean time of postmenstrual age (PMA) at IVC treatment were 1,174.0 ± 446.0 g, 28.4 ± 3.0 weeks, and 37.1 ± 1.6 weeks, respectively; for the female group, they were 1,108 ± 285.5 g, 28.2 ± 2.5 weeks, and 36.8 ± 2.1 weeks, respectively. For the male group, the IOP at baseline, 2 min, 1 h, 1 day, and 1 week after IVC were 12.4 ± 1.5 mmHg, 49.0 ± 3.1 mmHg, 26.3 ± 2.5 mmHg, 13.4 ± 2.2 mmHg, and 11.6 ± 1.7 mmHg, respectively; for the female group, they were 10.7 ± 2.0 mmHg, 47.3 ± 3.2 mmHg, 26.4 ± 3.2 mmHg, 10.7 ± 1.8 mmHg, and 10.2 ± 1.8 mmHg, respectively. In both groups, the IOP immediately (2 min) after the operation was significantly higher than that at any other time point (p < 0.01). IOP values returned to the preoperative baseline level on the first day after surgery, with no significant difference compared with that before injection (p > 0.05). IOP continued to be maintained at the preoperative baseline level on the first week after surgery, with no significant difference compared with that before surgery (p > 0.05).

Conclusion: Infants with ROP who received IVC experienced a sharp increase in the IOP immediately after injection, which decreased to below 30 mmHg after 1 h and maintain that level for 1 week or longer.
Targeting intestinal microecology: potential intervention strategies of traditional Chinese medicine for managing hypertension
Authors: Yang Zhihua , Lin Shanshan , Liu Yangxi , Song Zhihui , Ge Zhao , Fan Yujian , Chen Lu , Bi Yingfei , Zhao Zhiqiang , Wang Xianliang , Wang Yi , Mao Jingyuan
Published: May 2023

Hypertension has become one of the major public health problems in the world. At present, the pathogenesis of hypertension has still not been completely elucidated. In recent years, an increasing evidence shows that intestinal microecology is closely related to hypertension, which provides a new thinking for the prevention and treatment of hypertension. Traditional Chinese medicine (TCM) has unique advantages in the treatment of hypertension. Taking intestinal microecology as the target, it is possible to interpreting the scientific connotation of TCM prevention and treatment of hypertension by updating the treatment concept of hypertension, so as to improve the therapeutic effect. In our study, the clinical evidence for TCM treatment of hypertension was systematicly summarized. And the relationship among TCM, intestinal microecology and hypertension was analyzed. In addition, the methods by which TCM regulates intestinal microecology to prevent and treat hypertension were presented, to provide new research ideas for prevention and treatment of hypertension.
Genetic alterations and molecular mechanisms underlying hereditary intrahepatic cholestasis
Authors: Xie Shuying , Wei Shizhang , Ma Xiao , Wang Ruilin , He Tingting , Zhang Zhao , Yang Ju , Wang Jiawei , Chang Lei , Jing Manyi , Li Haotian , Zhou Xuelin , Zhao Yanling
Published: May 2023

Hereditary cholestatic liver disease caused by a class of autosomal gene mutations results in jaundice, which involves the abnormality of the synthesis, secretion, and other disorders of bile acids metabolism. Due to the existence of a variety of gene mutations, the clinical manifestations of children are also diverse. There is no unified standard for diagnosis and single detection method, which seriously hinders the development of clinical treatment. Therefore, the mutated genes of hereditary intrahepatic cholestasis were systematically described in this review.
Computational and experimental pharmacology to decode the efficacy of Theobroma cacao L. against doxorubicin-induced organ toxicity in EAC-mediated solid tumor-induced mice
Authors: Patil Priyanka P. , Kumar Pranjal , Khanal Pukar , Patil Vishal S. , Darasaguppe Harish R. , Bhandare Vishwambhar Vishnu , Bhatkande Arati , Shukla Sudhanshu , Joshi Rajesh K. , Patil Basanagouda M. , Roy Subarna
Published: May 2023

Background and objective: Doxorubicin is extensively utilized chemotherapeutic drug, and it causes damage to the heart, liver, and kidneys through oxidative stress. Theobroma cacao L (cocoa) is reported to possess protective effects against several chemical-induced organ damages and also acts as an anticancer agent. The study aimed to determine whether the administration of cocoa bean extract reduces doxorubicin-induced organ damage in mice with Ehrlich ascites carcinoma (EAC) without compromising doxorubicin efficacy.

Methodology: Multiple in vitro methods such as cell proliferation, colony formation, chemo-sensitivity, and scratch assay were carried out on cancer as well as normal cell lines to document the effect of cocoa extract (COE) on cellular physiology, followed by in vivo mouse survival analysis, and the organ-protective effect of COE on DOX-treated animals with EAC-induced solid tumors was then investigated. In silico studies were conducted on cocoa compounds with lipoxygenase and xanthine oxidase to provide possible molecular explanations for the experimental observations.

Results:In vitro studies revealed potent selective cytotoxicity of COE on cancer cells compared to normal. Interestingly, COE enhanced DOX potency when used in combination. The in vivo results revealed reduction in EAC and DOX-induced toxicities in mice treated with COE, which also improved the mouse survival time; percentage of lifespan; antioxidant defense system; renal, hepatic, and cardiac function biomarkers; and also oxidative stress markers. COE reduced DOX-induced histopathological alterations. Through molecular docking and MD simulations, we observed chlorogenic acid and 8′8 methylenebiscatechin, present in cocoa, to have the highest binding affinity with lipoxygenase and xanthine oxidase, which lends support to their potential in ameliorating oxidative stress.

Conclusion: The COE reduced DOX-induced organ damage in the EAC-induced tumor model and exhibited powerful anticancer and antioxidant effects. Therefore, COE might be useful as an adjuvant nutritional supplement in cancer therapy.
Modulating retinoid-X-receptor alpha (RXRA) expression sensitizes chronic myeloid leukemia cells to imatinib in vitro and reduces disease burden in vivo
Authors: Rajamani Bharathi M. , Illangeswaran Raveen Stephen Stallon , Benjamin Esther Sathya Bama , Balakrishnan Balaji , Jebanesan Daniel Zechariah Paul , Das Saswati , Pai Aswin Anand , Vidhyadharan Rakhi Thalayattu , Mohan Ajith , Karathedath Sreeja , Abraham Aby , Mathews Vikram , Velayudhan Shaji R. , Balasubramanian Poonkuzhali
Published: May 2023

Introduction: The ligand-activated transcription factors, nuclear hormone receptors (NHRs), remain unexplored in hematological malignancies except for retinoic acid receptor alpha (RARA).

Methods: Here we profiled the expression of various NHRs and their coregulators in Chronic myeloid leukemia (CML) cell lines and identified a significant differential expression pattern between inherently imatinib mesylate (IM)-sensitive and resistant cell lines.

Results: Retinoid-X-receptor alpha (RXRA) was downregulated in CML cell lines inherently resistant to IM and in primary CML CD34+ cells. Pre-treatment with clinically relevant RXRA ligands improved sensitivity to IM in-vitro in both CML cell lines and primary CML cells. This combination effectively reduced the viability and colony-forming capacity of CML CD34+ cells in-vitro. In-vivo, this combination reduced leukemic burden and prolonged survival. Overexpression (OE) of RXRA inhibited proliferation and improved sensitivity to IM in-vitro. In-vivo, RXRA OE cells showed reduced engraftment of cells in the bone marrow, improved sensitivity to IM, and prolonged survival. Both RXRA OE and ligand treatment markedly reduced BCR::ABL1 downstream kinase activation, activating apoptotic cascades and improving sensitivity to IM. Importantly, RXRA OE also led to the disruption of the oxidative capacity of these cells.

Conclusion: Combining IM with clinically available RXRA ligands could form an alternative treatment strategy in CML patients with suboptimal response to IM.
Does China’s centralized volume-based drug procurement policy facilitate the transition from imitation to innovation for listed pharmaceutical companies? Empirical tests based on double difference model
Authors: Gu Yang , Zhuang Qian
Published: May 2023

Introduction: The normalized implementation of the centralized volume-based procurement policy for pharmaceuticals is a concerted push for supply-side structural reform of the pharmaceutical industry in China. The impact of the centralized drug procurement policy on pharmaceutical companies' transition from imitation to innovation is investigated to test whether a positive effect occurs in the innovation landscape of the pharmaceutical market.

Methods: The double difference method and a series of robustness tests were used based on data from a sample of listed pharmaceutical companies in Shanghai and Shenzhen A-shares between 2015 and 2021.

Results: The study found that the centralized drug procurement policy significantly contributed to the increased intensity of innovation input in the Chinese pharmaceutical industry. In terms of regional and firm nature heterogeneity, it was found that firms in the seven provinces belonging to the three economic regions had a better increase in innovation input intensity than other regions. Firms of state-owned nature had a better increase in innovation input intensity than private companies. The mechanism test found a partial mediating effect of nearly 10% for the cost of sales rate on the innovation input intensity of listed companies and a negative mediating effect on corporate operating profit.

Discussion: Further research found that the effect of centralized drug procurement policy on the improvement of innovation quality of listed pharmaceutical companies was evident. The innovation development of Chinese pharmaceutical companies no longer focused on the accumulation of innovation quantity.
RIPK2: a promising target for cancer treatment
Authors: You Jieqiong , Wang Ying , Chen Haifeng , Jin Fang
Published: May 2023

As an essential mediator of inflammation and innate immunity, the receptor-interacting serine/threonine-protein kinase-2 (RIPK2) is responsible for transducing signaling downstream of the intracellular peptidoglycan sensors nucleotide oligomerization domain (NOD)-like receptors 1 and 2 (NOD1/2), which will further activate nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, leading to the transcription activation of pro-inflammatory cytokines and productive inflammatory response. Thus, the NOD2-RIPK2 signaling pathway has attracted extensive attention due to its significant role in numerous autoimmune diseases, making pharmacologic RIPK2 inhibition a promising strategy, but little is known about its role outside the immune system. Recently, RIPK2 has been related to tumorigenesis and malignant progression for which there is an urgent need for targeted therapies. Herein, we would like to evaluate the feasibility of RIPK2 being the anti-tumor drug target and summarize the research progress of RIPK2 inhibitors. More importantly, following the above contents, we will analyze the possibility of applying small molecule RIPK2 inhibitors to anti-tumor therapy.
Investigating the effect of Icaritin on hepatocellular carcinoma based on network pharmacology
Authors: Xue Zhong , Zhang Fan , Xu Shaohua , Chen Minyong , Wang Mingzuo , Wang Ming , Ke Fayong , Chen Zhaoshuo , Zhang Mingji
Published: May 2023

Hepatocellular carcinoma is one of the cancers that kill people in the global population. Icaritin, a small molecule drug approved by NMPA, has demonstrated potential anti-HCC effects. However, its underlying molecular mechanisms remain unclear. We employed a multi-omics approach in this study, including pharmaco-omics and proteomics, to look into the Icaritin’s possible molecular targets and workings in the therapy of HCC. Through pharmaco-omics analysis, we identified ten putative target genes of Icaritin, including FYN. The relationship between Icaritin and these target genes, particularly FYN, was further validated through in vitro and in vivo experiments. The outcomes revealed that Icaritin may exert its anti-HCC effects through modulating the FYN gene, highlighting the importance of multi-omics approaches in drug discovery research. This research gives valuable insights regarding the therapeutic potential of Icaritin against HCC and its possible molecular mechanisms.
In silico analysis of angiotensin-converting enzyme inhibitory compounds obtained from soybean [Glycine max (L.) Merr.]
Authors: Ramlal Ayyagari , Bhat Isha , Nautiyal Aparna , Baweja Pooja , Mehta Sahil , Kumar Vikash , Tripathi Shikha , Mahto Rohit Kumar , Saini Manisha , Mallikarjuna Bingi Pujari , Saluja Shukla , Lal S. K. , Subramaniam Sreeramanan , Fawzy Iten M. , Rajendran Ambika
Published: May 2023

Cardiovascular diseases (CVDs) are one of the major reasons for deaths globally. The renin–angiotensin–aldosterone system (RAAS) regulates body hypertension and fluid balance which causes CVD. Angiotensin-converting enzyme I (ACE I) is the central Zn-metallopeptidase component of the RAAS playing a crucial role in maintaining homeostasis of the cardiovascular system. The available drugs to treat CVD have many side effects, and thus, there is a need to explore phytocompounds and peptides to be utilized as alternative therapies. Soybean is a unique legume cum oilseed crop with an enriched source of proteins. Soybean extracts serve as a primary ingredient in many drug formulations against diabetes, obesity, and spinal cord-related disorders. Soy proteins and their products act against ACE I which may provide a new scope for the identification of potential scaffolds that can help in the design of safer and natural cardiovascular therapies. In this study, the molecular basis for selective inhibition of 34 soy phytomolecules (especially of beta-sitosterol, soyasaponin I, soyasaponin II, soyasaponin II methyl ester, dehydrosoyasaponin I, and phytic acid) was evaluated using in silico molecular docking approaches and dynamic simulations. Our results indicate that amongst the compounds, beta-sitosterol exhibited a potential inhibitory action against ACE I.
The effects of essential oil from Lippia origanoides and herbal betaine on performance, intestinal integrity, bone mineralization and meat quality in broiler chickens subjected to cyclic heat stress
Authors: Señas-Cuesta Roberto , Stein Andressa , Latorre Juan D. , Maynard Clay J. , Hernandez-Velasco Xochitl , Petrone-Garcia Victor , Greene Elizabeth S. , Coles Makenly , Gray Latasha , Laverty Lauren , Martin Kristen , Loeza Ileana , Uribe Alvaro J. , Martínez Blanca C. , Angel-Isaza Jaime A. , Graham Danielle , Owens Casey M. , Hargis Billy M. , Tellez-Isaias Guillermo
Published: May 2023

Essential oils (EO) affect performance, intestinal integrity, bone mineralization, and meat quality in broiler chickens subjected to cyclic heat stress (HS). Day-of-hatch Cobb 500 male broiler chicks (n = 475) were randomly divided into four groups. Group 1: No heat stress (Thermoneutral) + control diets with no antibiotics; Group 2: heat stress control + control diets; Group 3: heat stress + control diets supplemented with thymol chemotype (45 ppm) and herbal betaine (150 ppm) formulation EO1; Group 4: heat stress + control diets supplemented with phellandrene (45 ppm) and herbal betaine (150 ppm) formulation EO2. From day 10–42, the heat stress groups were exposed to cyclic HS at 35°C for 12 h (8:00–20:00). BW, BWG, FI, and FCRc were measured at d 0, 10, 28, and 42. Chickens were orally gavaged with FITC-d on days 10 (before heat stress) and 42. Morphometric analysis of duodenum and ileum samples and bone mineralization of tibias were done. Meat quality was assessed on day 43 with ten chickens per pen per treatment. Heat stress reduced BW by day 28 (p < 0.05) compared to thermoneutral chickens. At the end of the trial, chickens that received both formulations of EO1 and EO2 had significantly higher BW than HS control chickens. A similar trend was observed for BWG. FCRc was impaired by EO2 supplementation. There was a significant increase in total mortality in EO2 compared with EO1 EO1 chickens had lower FITC-d concentrations at day 42 than the HS control. In addition, EO1 treatment is not statistically different if compared to EO2 and thermoneutral. Control HS broilers had significantly lower tibia breaking strength and total ash at day 42 than heat-stressed chickens supplemented with EO1 and EO2. Heat stress affected intestinal morphology more than thermoneutral chickens. EO1 and EO2 improved intestinal morphology in heat-stressed chickens. Woody breast and white striping were more common in thermoneutral chickens than heat stress chickens. In conclusion, the EO-containing diet could improve broiler chicken growth during cyclic heat stress, becoming increasingly relevant in antibiotic-free production in harsh climates.
A rapid-crosslinking antimicrobial hydrogel with enhanced antibacterial capabilities for improving wound healing
Authors: Zhang Xi , Li Wanxin , Wei Genying , Yan Yuling , He Ruitao , Wang Yan , Chen Daoyuan , Qin Xiaofei
Published: May 2023

One of the main reasons impeding wound healing is wound infection caused by bacterial colonization with a continuous stage of inflammation. Traditional wound treatments like gauze are being replaced by tissue adhesives with strong wet tissue adhesion and biocompatibility. Herein, a fast-crosslinking hydrogel is developed to achieve both strong antimicrobial properties and excellent biocompatibility. In this study, a simple and non-toxic composite hydrogel was prepared by the Schiff base reaction between the aldehyde group of 2,3,4-trihydroxybenzaldehyde (TBA) and the amino group of ε-Poly-L-lysine (EPL). Subsequently, a succession of experiments toward this new hydrogel including structure characterization, antimicrobial properties, cell experiment and wound healing were applied. The results of the experiments show that the EPL-TBA hydrogel not only exhibited excellent contact-active antimicrobial activities against Gram-negative bacteria Escherichia coli (E. coil) and Gram-positive Bacteria Staphylococcus aureus (S. aureus), but also inhibited the biofilm formation. More importantly, the EPL-TBA hydrogel promoted the wound healing with low cytotoxicity in vivo. These findings indicate that the EPL-TBA hydrogel has a promising use as a wound dressing in the bacterial infection prevention and wounds healing acceleration.
Variation and stability of rhizosphere bacterial communities of Cucumis crops in association with root-knot nematodes infestation
Authors: Song Liqun , Ping Xingxing , Mao Zhenchuan , Zhao Jianlong , Yang Yuhong , Li Yan , Xie Bingyan , Ling Jian
Published: May 2023

Introduction

Root-knot nematodes (RKN) disease is a devastating disease inCucumiscrops production. Existing studies have shown that resistant and susceptible crops are enriched with different rhizosphere microorganisms, and microorganisms enriched in resistant crops can antagonize pathogenic bacteria. However, the characteristics of rhizosphere microbial communities ofCucumiscrops after RKN infestation remain largely unknown.

Methods

In this study, we compared the changes in rhizosphere bacterial communities between highly RKN-resistantCucumis metuliferus(cm3) and highly RKN-susceptibleCucumis sativus(cuc) after RKN infection through a pot experiment.

Results

The results showed that the strongest response of rhizosphere bacterial communities ofCucumiscrops to RKN infestation occurred during early growth, as evidenced by changes in species diversity and community composition. However, the more stable structure of the rhizosphere bacterial community in cm3 was reflected in less changes in species diversity and community composition after RKN infestation, forming a more complex and positively co-occurrence network than cuc. Moreover, we observed that both cm3 and cuc recruited bacteria after RKN infestation, but the bacteria enriched in cm3 were more abundant including beneficial bacteria Acidobacteria, Nocardioidaceae and Sphingomonadales. In addition, the cuc was enriched with beneficial bacteria Actinobacteria, Bacilli and Cyanobacteria. We also found that more antagonistic bacteria than cuc were screened in cm3 after RKN infestation and most of them werePseudomonas(Proteobacteria, Pseudomonadaceae), and Proteobacteria were also enriched in cm3 after RKN infestation. We hypothesized that the cooperation between Pseudomonas and the beneficial bacteria in cm3 could inhibit the infestation of RKN.

Discussion

Thus, our results provide valuable insights into the role of rhizosphere bacterial communities on RKN diseases ofCucumiscrops, and further studies are needed to clarify the bacterial communities that suppress RKN inCucumiscrops rhizosphere.