Therapy Research Articles

High prevalence of carbapenem-resistant Enterobacter cloacae complex in a tertiary hospital over a decade.

The emergence and spread of the carbapenem-resistant Enterobacter cloacae complex (CRECC) have become a significant public health problem. CRECC strains frequently harbor multiple drug resistance genes and can be epidemic within healthcare facilities. The study explored the characteristics and prevalence of CRECC strains in the same hospital over a decade, which provides a theoretical basis for epidemiologic surveillance and clinical treatment.

Evaluation of Anti-Alzheimer's Potential of Azo-Stilbene-Thioflavin-T derived Multifunctional Molecules: Synthesis, Metal and Aβ Species Binding and Cholinesterase Activity.

Inhibition of amyloid β (Aβ) aggregation and cholinesterase activity are two major therapeutic targets for Alzheimer's disease (AD). Multifunctional Molecules (MFMs) specifically designed to address other contributing factors, such as metal ion induced abnormalities, oxidative stress, toxic Ab aggregates etc. are very much required. Several multifunctional molecules have been developed using different molecular scaffolds. Reported herein is a new series of four MFMs based on ThT, Azo-stilbene and metal ion chelating pockets. The synthesis, characterization, and metal chelation ability for [Cu(II) and Zn(II)] are presented herein. Furthermore, we explored their multifunctionality w.r.t. to their (i) recognition of Aβ aggregates and monomeric form, (ii) utility in modulating the aggregation pathways of both metal-free and metal-bound amyloid-β, (iii) ex-vivo staining of amyloid plaques in 5xFAD mice brain sections, (iv) ability to scavenge free radicals and (v) ability to inhibit cholinesterase activity. Molecular docking studies were also performed with Aβ peptides and acetylcholinesterase enzyme to understand the observed inhibitory effect on activity. Overall, the studies presented here establish the multifunctional nature of these molecules and qualify them as promising candidates for furthermore investigation in the quest for finding Alzheimer's disease treatment.

Chemical Tools for Monitoring and Targeting Collagen Cross-linking.

The formation of collagen, the most abundant protein in mammals, is vital for the integrity of skin, tendons, and tissue in essentially any organ. Excessive collagen formation is, however, characteristic of fibrotic and malignant diseases, which include major global health issues. The diagnosis of abnormal collagen production and deposition is, therefore, critical for disease prognosis and helps guide treatment decisions. Here, we summarize our research on the development of tailored tools for monitoring and targeting excessive collagen crosslinking. We anticipate these tools will provide a deep understanding at the molecular level of collagen formation in normal and disease conditions with applications in imaging and disease treatment.

Being associated with multiple diseases, CD79a, as a B-cell marker plays an important role in disease treatment and prognosis

CD79a, a membrane glycoprotein critical for B-cell receptor (BCR) signaling, plays a vital role in B-cell development and immune responses. It serves as a marker for normal and tumor B-cells and is implicated in the progression of various diseases, including B-cell lymphomas, leukemia, autoimmune disorders, and other systemic diseases such as neurological, hematological, and respiratory disorders. This review provides a comprehensive analysis of the discovery, molecular structure, and function of CD79a, along with its regulatory mechanisms at the transcriptional and post-translational levels. CD79a’s involvement in signaling pathways and its potential as a therapeutic target for novel treatments, such as chimeric antigen receptor-T (CAR-T) cell therapy and bispecific antibodies, are also explored. The review highlights emerging therapeutic strategies targeting CD79a, emphasizing its significance in the prognosis of CD79a-related diseases and the ongoing need for further research to optimize clinical interventions.

Challenges and Opportunities in the Clinical Translation of High-Resolution Spatial Transcriptomics.

Pathology has always been fueled by technological advances. Histology powered the study of tissue architecture at single-cell resolution and remains a cornerstone of clinical pathology today. In the last decade, next-generation sequencing has become informative for the targeted treatment of many diseases, demonstrating the importance of genome-scale molecular information for personalized medicine. Today, revolutionary developments in spatial transcriptomics technologies digitalize gene expression at subcellular resolution in intact tissue sections, enabling the computational analysis of cell types, cellular phenotypes, and cell-cell communication in routinely collected and archival clinical samples. Here we review how such molecular microscopes work, highlight their potential to identify disease mechanisms and guide personalized therapies, and provide guidance for clinical study design. Finally, we discuss remaining challenges to the swift translation of high-resolution spatial transcriptomics technologies and how integration of multimodal readouts and deep learning approaches is bringing us closer to a holistic understanding of tissue biology and pathology.

Primary hyperoxaluria type 3: from infancy to adulthood in a genetically unique cohort.

Primary hyperoxaluria type 3 (PH3) is a rare autosomal recessive disorder caused by bi-allelic genetic variants in the 4 hydroxy-2 oxoglutarate aldolase (HOGA-1) gene. We report the natural history of PH3 in a 16-patient cohort, 15 from a unique genetically isolated population. This retrospective single-center study followed PH3 patients between 2003 and 2023 with demographic, clinical, radiographic, genetic, and biochemical parameters. Genetic population screening was performed in four villages to determine carrier frequency and identify couples at risk in a genetically isolated population. Sixteen patients with biallelic (or homozygous) pathogenic variants (PV) in HOGA-1 (c.944_946 del, c.119C > A, c.208C > T) were included in the study, 15 Druze and one Jewish, aged 0-63years at diagnosis (4 adults and 12 pediatric patients). All symptomatic patients had clinical or imaging signs of nephrolithiasis. One developed chronic kidney disease (CKD) stage 5; biopsy showed focal mesangial sclerosis and chronic tubulo-interstitial changes with few oxalate deposits. Two other patients had CKD stage 2 (eGFR 87 and 74mL/min/1.73m2) upon their last visit. The remaining cohort showed preserved kidney function until the latest follow-up. Of 1167 healthy individuals screened, 90 carriers were found, a rate of 1:13 in the genetically unique cohort screened. A high prevalence of PH3 patients was found among a unique cohort, but probably still underdiagnosed due to relatively mild disease course. The carrier rate is high. There is no specific therapy for PH3, but early diagnosis can prevent redundant diagnostic efforts and provide early treatment for kidney stone disease. Even in our homogeneous cohort, kidney stone disease severity and CKD degree were variable, supporting a suspected contribution of yet unknown genetic or environmental factors.

Targeting ferroptosis: a novel therapeutic strategy for the treatment of retinal diseases

Ferroptosis plays a vital role in the progression of various retinal diseases. The analysis of the mechanism of retinal cell ferroptosis has brought new targeted strategies for treating retinal vascular diseases, retinal degeneration and retinal nerve diseases, and is also a major scientific issue in the field of ferroptosis. In this review, we summarized results from currently available in vivo and in vitro studies of multiple eye disease models, clarified the pathological role and molecular mechanism of ferroptosis in retinal diseases, summed up the existing pharmacological agents targeting ferroptosis in retinal diseases as well as highlighting where future research efforts should be directed for the application of ferroptosis targeting agents. This review indicates that ferroptosis of retinal cells is involved in the progression of age-related/inherited macular degeneration, blue light-induced retinal degeneration, glaucoma, diabetic retinopathy, and retinal damage caused by retinal ischemia-reperfusion via multiple molecular mechanisms. Nearly 20 agents or extracts, including iron chelators and transporters, antioxidants, pharmacodynamic elements from traditional Chinese medicine, ferroptosis-related protein inhibitors, and neuroprotective agents, have a remissioning effect on retinal disease in animal models via ferroptosis inhibition. However, just a limited number of agents have received approval or are undergoing clinical trials for conditions such as iron overload-related diseases. The application of most ferroptosis-targeting agents in retinal diseases is still in the preclinical stage, and there are no clinical trials yet. Future research should focus on the development of more potent ferroptosis inhibitors, improved drug properties, and ideally clinical testing related to retinal diseases.

Rouviere’s Sulcus: Frequency and Types among Patients presented to Wad Madani Teaching Hospital for Laparoscopic Cholecystectomy; Gezira State; Sudan

Scientific background: Laparoscopic cholecystectomy is the gold standard for surgical treatment of gallstones disease. Method: The study aimed to determine presence and types of Rouviere’s sulcus along with its association with gender, and postoperative morbidity among Sudanese patients presented for laparoscopic cholecystectomy, and operated on at Wad Madani Teaching Hospital, Gezira State, Sudan; during the period from November 2022 to November 2023. It was a comparative cross-sectional study. Study population were patients of more than 18 years old; where total coverage of them (150) was done. Data was collected from files and records of patients presented there during study period. Master sheet was used for data collection. SPSS version 25.0 was used for analysis. P-value ≤ 0.05 was considered significant. Results: Age of participants ranged from 17 to 85 years, with a mean age of 47.57 (SD ± 15.14). Majority of them were female (93.3%). Gallstones were present in 99.3%. Rouviere’s sulcus was identified intraoperatively among 92.7%. Identified sulcus type was: Open sulcus (54.0%), Close sulcus (27.3%), and Scar sulcus (11.3%). Postoperative operative outcomes: 95.3% experienced uneventful outcomes; and 4.7% experienced complications. Both postoperative complications and gender, had no statistical associations with the presence of Rouviere’s sulcus; P-value = 0.470, and 0.112 respectively. Also, there was no significant statistical association between gender and sulcus type (P-value 0.301). Conclusion and recommendations: No significant statistical association between both postoperative complications and gender with the presence of Rouviere’s sulcus, or between gender and sulcus type; was identified. Further study was highly recommended.

The role of the cGAS-STING pathway in chronic pulmonary inflammatory diseases

The innate immune system plays a vital role in the inflammatory process, serving as a crucial mechanism for the body to respond to infection, cellular stress, and tissue damage. The cGAS-STING signaling pathway is pivotal in the onset and progression of various autoimmune diseases and chronic inflammation. By recognizing cytoplasmic DNA, this pathway initiates and regulates inflammation and antiviral responses within the innate immune system. Consequently, the regulation of the cGAS-STING pathway has become a prominent area of interest in the treatment of many diseases. Chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD), asthma, and pulmonary fibrosis, are characterized by persistent or recurrent lung inflammation and tissue damage, leading to diminished respiratory function. This paper explores the mechanism of action of the cGAS-STING signaling pathway in these diseases, examines the development of STING inhibitors and nanomaterial applications, and discusses the potential clinical application prospects of targeting the cGAS-STING pathway in chronic inflammatory lung diseases.

3DSTarPred: A Web Server for Target Prediction of Bioactive Small Molecules Based on 3D Shape Similarity.

Target identification plays a critical role in preclinical drug development. The in silico approach has been developed and widely applied to assist medicinal chemists and pharmacologists in drug target identification. There are many target prediction web servers available today that have revealed both advantages and shortcomings in practical applications. Here, we present 3DSTarPred, a web server for three-dimensional (3D) shape similarity-based target prediction of small molecules. A benchmark study showed that 3DSTarPred achieved a target prediction success rate of 76.27%, which was higher than that of existing target prediction web servers. In addition, the performance of 3DSTarPred in the target prediction of diverse substructures/superstructures was also better than that of the existing target prediction web servers. In case studies, 3DSTarPred was used to identify the potential targets of two small molecules, one being kaempferol, a natural lead compound for the treatment of Alzheimer's disease (AD), and the other being sildenafil, a candidate for drug repurposing in AD. The case studies further demonstrated the reliability and success of 3DSTarPred in practice. The 3DSTarPred server is freely available at http://3dstarpred.pumc.wecomput.com.

A kidney-specific fasting-mimicking diet induces podocyte reprogramming and restores renal function in glomerulopathy.

Cycles of a fasting-mimicking diet (FMD) promote regeneration and reduce damage in the pancreases, blood, guts, and nervous systems of mice, but their effect on kidney disease is unknown. In addition, a FMD has not been tested in rats. Here, we show that cycles of a newly developed low-salt FMD (LS-FMD) restored normal proteinuria and nephron structure and function in rats with puromycin-induced nephrosis compared with that in animals with renal damage that did not receive the dietary intervention. LS-FMD induced modulation of a nephrogenic gene program, resembling renal developmental processes in multiple kidney structures. LS-FMD also activated podocyte-lineage reprogramming pathways and promoted a quiescent state in mature podocytes in the rat kidney damage model. In a pilot clinical study in patients with chronic kidney disease, FMD cycles of 5 days each month for 3 months promoted renoprotection, including reduction of proteinuria and improved endothelial function, compared with that in patients who did not receive the FMD cycles. These results show that FMD cycles, which promote the reprogramming of multiple renal cell types and lead to glomerular damage reversal in rats, should be tested further for the treatment of progressive kidney diseases.

Research progress on the application of virtual artificial intelligence in risk assessment and diagnosis of periodontal disease

Periodontal disease is a common and frequently-occurring disease in China. Early detection, diagnosis, and treatment of periodontal disease are of great significance for achieving universal oral health and even systemic health. Artificial intelligence endows machines with the ability to mimic human intelligent behavior, and is commonly used in medical field with both physical and virtual forms. Virtual artificial intelligence empowers traditional experience in the application of periodontal disease risk assessment and diagnosis, with the potential to develop a variety of oral health screening tools. It helps to provide new evidence for the prognosis of periodontal disease, improve the accuracy and efficiency of diagnosis, reduce technical sensitivity and further promote the periodontal treatment transformation from "treatment-oriented" to "prevention-oriented". This paper reviews the current applications and progresses of virtual artificial intelligence in periodontal risk assessment and diagnosis, as well as its limitations, providing ideas for future researches on the application of virtual artificial intelligence in this field.

The Rhizome of Atractylodes macrocephala Koidz.: A Comprehensive Review on the Traditional Uses, Phytochemistry and Pharmacology.

Atractylodes macrocephala Koidz. (A. macrocephala) is a perennial herb of the genus Atractylodes. The rhizome of A. macrocephala (AMR) is its medicinal part. It primarily grows in Southeast Asia and function to invigorate the spleen and qi, drying dampness and removing water. It has long been used for cancer treatment, relieving inflammation, and improving gastrointestinal function, highlighting its remarkable medicinal value. This paper focuses on recent advancements in the traditional uses, phytochemistry, and pharmacology of AMR from 2018 to the present, while exploring its therapeutic and scientific potential. In recent years, more than 120 compounds have been identified in AMR. The primary active components have been identified as sesquiterpenoids, polysaccharides and polyacetylenes. Modern pharmacological studies have demonstrated that AMR has anti-inflammatory, anti-tumor, immunity enhancement, gastrointestinal function improvement, and other pharmacological effects. It is mainly employed in the clinical treatment of tumors and gastrointestinal diseases, showing promising developmental potential. Its mechanism may be related to reducing oxidative stress, inhibiting the expression of inflammatory mediators and factors, and alleviating apoptosis through related signaling pathways. It is hoped that this review can provide a theoretical reference and scientific basis for further systematic research and extensive clinical application of AMR.

O USO DE SORO HIPERIMUNE NA CLÍNICA DE PEQUENOS ANIMAIS

The immune system is intended to defend the body against harmful invaders. Antibodies are largely responsible for defense against pathogenic antigens. The immunological defense of some conditions, both innate and acquired, may have nonspecific production and insufficient antibodies to combat them. The use of hyperimmune serum can be an alternative in defending the body against specific pathogens, a procedure which transfers antibodies ready for defense against antigens. This therapy consists of using plasma or serum extracted by centrifugation from the blood of an animal previously vaccinated or already cured of a specific disease. The serum is offered to an animal that has had a failure in the vaccination protocol or has contracted a certain disease. The objective of this study was to carry out a literature review regarding the use and application of hyperimmune serum in small animals. Also used as complementary therapy, hyperimmune serum has demonstrated excellent results in reducing free antigens in the serum of patients affected by certain pathologies. It proved to be relevant in clinically improving recovery from diseases such as distemper and parvovirus. This technique presents a promising prognosis, but there are many studies to be carried out to effectively prove the application of hyperimmune serum in the complementary treatment of certain diseases that affect dogs and cats.

A study of CPITN score in Periodontics Clinic Patients, RSGM Airlangga University, 2022

Background: Approximately 90% of the global population suffers from periodontal disesase, characterizes by bleeding gums, pain, and bad breath. The impact of this disease is diverse, ranging from tooth loss, disruption of aesthetics and confidence, to influencing individual nutritional status. The disease can be caused by damage of the periodontal tissues. Therefore, the Community Periodontal Index of Treatment Needs (CPITN) is highly essential for assessing the extend of issues in periodontal tissues, including evaluating oral and dental health problems in patients. This assessment can aid in the treatment and prevention of periodontal disease. Material and Methods: This research is a descriptive study. The population consists of all patients who visited the periodontology clinic at the Faculty of Dentistry, Airlangga University, in the year 2022. The sample was taken using a total sampling technique, involving secondary data obtained from the periodontal status cards of patients, specifically focusing on the examination data related to the condition of periodontal tissues based on the Community Periodontal Index of Treatment Needs (CPITN). Conclusion: The CPITN scores vary between gender and age groups of the patients. Therefore, bivariate research is needed to analyze the relationship of these parameters with the CPITN scores of periodontology patients.

In vitro antibacterial activity of Morinda citrifolia extracts against eight pathogenic bacteria species.

Medical professionals continue to face a severe issue with the evolution of resistance to conventional antibiotics. The search for new novel compounds from plants has been proven to be the alternative solution. Morinda citrifolia is used traditionally for the treatment of infectious diseases. The present study investigates the antibacterial properties of M. citrifolia root, leaf, and fruit (fresh, dried, and fermented) extracts on three-gram-positive and five-gram-negative bacteria. The plant parts were processed and extracted in distilled water and ethanol (60%, 80%, and absolute (100%)). The antibacterial activities of the extracts were assessed in vitro using the agar well diffusion method, with Ciprofloxacin serving as the positive control. All the tests were conducted three times to obtain the average value of inhibition zones. Overall, root extracts showed the most significant antibacterial activity, followed by dried fruit, fermented fruit extract, fresh fruit, and the least leaf extract. Using one-way ANOVA and Tukey's post-hoc tests, the statistical analysis revealed significant differences in antibacterial activity among the extracts and solvent concentrations. The 100% ethanol extracts had significantly higher zones of inhibition compared to the other solvents. The most inhibitory activity was against Campylobacter spp. (21.33±1.80) for the 80% ethanol root extract. All the extracts of M. citrifolia were found to exhibit moderate antibacterial activity against all the bacteria pathogens. However, Enterococcus faecium, Campylobacter spp., and Bacillus cereus were most sensitive to all the plant extracts while Shigella spp. and Klebsiella spp. showed resistance to most extracts. This observed difference is significant for each strain extract depending on the bacteria strain and the type of solvent extract (p < 0.001). The findings indicate a promising antimicrobial potential of M. citrifolia extracts.

Advancing CRISPR-Based Solutions for COVID-19 Diagnosis and Therapeutics

Since the onset of the COVID-19 pandemic, a variety of diagnostic approaches, including RT-qPCR, RAPID, and LFA, have been adopted, with RT-qPCR emerging as the gold standard. However, a significant challenge in COVID-19 diagnostics is the wide range of symptoms presented by patients, necessitating early and accurate diagnosis for effective management. Although RT-qPCR is a precise molecular technique, it is not immune to false-negative results. In contrast, CRISPR-based detection methods for SARS-CoV-2 offer several advantages: they are cost-effective, time-efficient, highly sensitive, and specific, and they do not require sophisticated instruments. These methods also show promise for scalability, enabling diagnostic tests. CRISPR technology can be customized to target any genomic region of interest, making it a versatile tool with applications beyond diagnostics, including therapeutic development. The CRISPR/Cas systems provide precise gene targeting with immense potential for creating next-generation diagnostics and therapeutics. One of the key advantages of CRISPR/Cas-based therapeutics is the ability to perform multiplexing, where different sgRNAs or crRNAs can target multiple sites within the same gene, reducing the likelihood of viral escape mutants. Among the various CRISPR systems, CRISPR/Cas13 and CARVER (Cas13-assisted restriction of viral expression and readout) are particularly promising. These systems can target a broad range of single-stranded RNA viruses, making them suitable for the diagnosis and treatment of various viral diseases, including SARS-CoV-2. However, the efficacy and safety of CRISPR-based therapeutics must be thoroughly evaluated in pre-clinical and clinical settings. While CRISPR biotechnologies have not yet been fully harnessed to control the current COVID-19 pandemic, there is an optimism that the limitations of the CRISPR/Cas system can be overcome soon. This review discusses how CRISPR-based strategies can revolutionize disease diagnosis and therapeutic development, better preparing us for future viral threats.

Dimorphandra gardneriana Tul. (Fabaceae): Medicinal and Industrial Potential of a Brazilian Plant with Pharmacological and Bioactive Properties

The traditional use of medicinal plants, particularly in the Middle East and Asia, highlights the historical and contemporary importance of these herbs in the treatment of various diseases and infections. Among these plants, the Fabaceae family stands out for its incredible diversity and significant therapeutic potential, including the genus Dimorphandra, which has demonstrated remarkable efficacy in several studies. Known as fava d'anta, Dimorphandra gardneriana is a plant native to Brazil with significant pharmacological properties, due to the presence of rutin, a flavonoid with anti-inflammatory and antioxidant effects. This study aims to consolidate data on Dimorphandra gardneriana, reviewing its chemical constituents, biological activities, and pharmacological properties to provide a comprehensive overview of its medicinal potential. The review was conducted based on published material and new data collected through databases such as MEDLINE, PUBMED, and SCOPUS. The process included defining the topic, inclusion/exclusion criteria, extraction and classification of studies, evaluation, and interpretation of the results. The analysis revealed that Dimorphandra gardneriana contains several bioactive compounds, such as rutin, galactomannans, and quercetin. These compounds have demonstrated antioxidant, anti-inflammatory, and antimicrobial properties. Combined with their use in advanced controlled release technologies and the application of silver nanoparticles, these properties highlight their value not only in natural medicine but also in industry. These promising characteristics indicate potential future biological activities in various fields of scientific and technological research, with the potential to significantly contribute to the development of new treatments and innovative products in diverse areas of well-being and other sectors, in addition to presenting significant financial value.

Doppler findings before and after endovascular treatment in peripheral artery disease

Doppler findings before and after endovascular treatment in peripheral artery disease

Liver Safety of Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease: interim Data from a Post-authorization Safety Study

Abstract Background After risk of drug-induced liver injury was detected during tolvaptan clinical development for the treatment of autosomal dominant polycystic kidney disease (ADPKD), a post-marketing pharmacovigilance study was required for EU regulatory approval. Methods This is an interim analysis from a prospective, observational study enrolling patients prescribed tolvaptan for ADPKD in routine clinical practice. Data were obtained through physician records collected during regular care. Per the prescribing label, liver transaminases were to be monitored monthly for the first 18 months of treatment and once every 3 months thereafter. Patients and physicians were required to report adverse events suggestive of serious and potentially fatal liver injury. Data collection was from October 2016–April 2022. Results Of 2074 patients (median follow-up, 528 days), in 75 (3.6%) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥ 3 x upper limit of normal (ULN) were reported. At data cutoff, the enzyme elevations were confirmed for 65 patients. Among the 65 confirmed patients, in addition to the transaminase elevations, there were 69 adverse events suggestive of liver injury. Tolvaptan was interrupted or withdrawn in 59/65 (90.8%) participants with confirmed ALT or AST ≥ 3 x ULN, with most transaminase elevations and adverse events resolved or resolving at data cutoff. No liver enzyme elevations met laboratory criteria for Hy's Law cases. Conclusions Transaminase elevations occurred post-marketing in a similar proportion of patients as reported in clinical trials (4.4–5.6%). Regular monitoring per label facilitates prompt detection of liver adverse events and intervention to mitigate risk of severe injury.