Advances in medical sciences最新文献

Purpose

The primary limiting factor in achieving cures for patients with cancer, particularly ovarian cancer, is drug resistance. The mechanisms of drug resistance of cancer cells during chemotherapy may include compounds of the extracellular matrix, such as the transforming growth factor-beta-induced protein (TGFBI). In this study, we aimed to analyze the TGFBI gene and protein expression in different sensitive and drug-resistant ovarian cancer cell lines, as well as test if TGFBI can be involved in the response to topotecan (TOP) at the very early stages of treatment.

Materials and methods

In this study, we conducted a detailed analysis of TGFBI expression in different ovarian cancer cell lines (A2780, A2780TR1, A2780TR2, W1, W1TR, SKOV-3, PEA1, PEA2 and PEO23). The level of TGFBI mRNA (QPCR), intracellular and extracellular protein (Western blot analysis) were assessed in this study.

Results

We observed upregulation of TGFBI mRNA in drug-resistant cell lines and estrogen-receptor positive cell lines, which was supported by overexpression of both intracellular and extracellular TGFBI protein. We also showed the TGFBI expression after a short period of treatment of sensitive ovarian cancer cell lines with TOP.

Conclusion

The expression of TGFBI in ovarian cancer cell lines suggests its role in the development of drug resistance.

Purpose

Atrophic gastritis, one of the processes leading to gastric cancer (GC), is closely related to Helicobacter pylori (HP) infection. This study aimed to understand how HP causes chronic inflammation that leads to ulcers and stomach problems.

Methods

Twenty-eight CAG patients were included in the study (9 HP-infected and 19 HP-uninfected). Endoscopy, histopathology, and high-throughput mRNA sequencing were performed. Differentially expressed genes (DEGs) were validated via qRT-PCR.

Results

Principal component analysis (PCA) results showed that more than 88.9 ​% of the samples were classified into the HP (+) group. A total of 157 DEGs were identified, of which 38 were up-regulated and 119 were down-regulated. The DEGs were mainly enriched in the biological process (BP) terms associated with immune system process, adaptive immune response, G protein-coupled receptor signaling pathway, as well as point to numerous key pathways, including fat digestion and absorption, retinol metabolism, steroid hormone biosynthesis, ascorbate and aldarate metabolism, and chemical carcinogenesis. APOA1, APOA4, FOXP3, NR1H4, ABCG5, ACTA1, CCL19, CCR7, CYP3A4, and PDCD had the highest degrees in protein–protein interaction network as the hub genes; they were also included into the transcription factor (TF)-target network except for PDCD. APOA1 and CYP3A4 were extremely significantly up-regulated in HP (+) CAG patients compared with the HP (−) CAG patients, while FOXP3, CCR7 and CCL19 were significantly down-regulated.

Conclusion

The expression of APOA1, CYP3A4, FOXP3, CCR7, and CCL19 are the potential indicators for CAG to GC development, being the biomarkers to predict progression of CAG and poor prognosis of GC.

Purpose

Bronchoalveolar lavage (BAL) procedure is a useful tool in the diagnosis of patients with interstitial lung disease (ILD) and is helpful in clinical research of chronic obstructive pulmonary disease (COPD) patients. Still little is known about predictors of poor BAL salvage. The trial aims to find the most efficient way to improve BAL recovery.

Material and methods

Our study is a prospective, multicenter, international, two-arm randomized controlled trial. We aim to obtain BAL samples from a total number of 300 patients: 150 with ILD and 150 with COPD to achieve a statistical power of 80 ​%. Patients with initial BAL salvage <60 ​% will be randomized into the non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP) arm. The NIV and CPAP will be set according to the study protocol. The influence on BAL salvage will be assessed in terms of BAL volume and content. Multivariable analysis of the additional test results to determine predictors for low BAL recovery will be conducted. In a study subgroup of approximately 20 patients per specific disease, a metabolomic assessment of exhaled air condensate will be performed. All procedures will be assessed in terms of the patient's safety. The trial was registered on clinicaltrials.gov (ID# NCT05631132). Interested experienced centers are invited to join the research group by writing to the corresponding author.

Conclusion

The results of our prospective study will address the currently unsolved problem of how to increase BAL salvage in patients with pulmonary diseases without increasing the risk of respiratory failure exacerbation.

Mesenchymal stem cells (MSCs) are being increasingly used in various therapeutic applications including skin tissue repair and wound healing. The positive effects of the MSCs therapy are largely elicited by immunomodulation, increasing angiogenesis, supporting extracellular matrix (ECM) and thus favoring skin structure. However, the therapeutic competences of MSC-based therapies are somewhat hindered by their apparent modest clinical merits, conferring the need for methods that would rise the efficacy of such therapies. A plethora of reports have shown that therapeutic properties of MSCs could be enhanced with other strategies and compounds like biomaterial and platelet-rich plasma (PRP) to target key possessions of MSCs and properties of adjacent tissues concurrently. Manipulation of cellular stress-response mechanisms to improve cell resistance to oxidative stress prior to or during MSC injection could also improve therapeutic efficacy of MSCs. In the current review, we shed light on the recent advances in MSCs combination therapy with other ingredients and procedures to sustain MSCs-mediated effects in wound healing.

Programmed cell death plays a crucial role in maintaining the homeostasis and integrity of multicellular organisms, and its dysregulation contributes to the pathogenesis of many diseases. Programmed cell death is regulated by a range of macromolecules and low-molecular messengers, including ceramides. Endogenous ceramides have different functions, that are influenced by their localization and the presence of their target molecules. This article provides an overview of the current understanding of ceramides and their impact on various types of programmed cell death, including apoptosis, anoikis, macroautophagy and mitophagy, and necroptosis. Moreover, it highlights the emergence of dihydroceramides as a new class of bioactive sphingolipids and their downstream targets as well as their future roles in cancer cell growth, drug resistance and tumor metastasis.

Purpose

In this study, it was aimed to determine the dose-dependent effects of hippocampal amyloid beta (Aβ) on frontal EEG activity and to elucidate the possible non-invasive biomarkers by recording spontaneous EEG in free-moving rats.

Material and methods

Male albino Wistar rats aged 3 months were randomly divided into 4 groups (n ​= ​8 for each group), obtained by intrahippocampal injection of saline or different doses of Aβ_1-42 i.e. 0.01 ​μg/μl, 0.1 ​μg/μl, and 1 ​μg/μl. After two weeks of recovery period, spontaneous EEG recordings were obtained from frontal regions and spectral power analyses were performed.

Results

We detected a general slowdown in the brain activity two weeks after Aβ_1-42 injection.

We observed significant increases in frontal alpha power (p ​= ​0.0021) and significant decreases in frontal beta power (p ​= ​0.0003) between the Sh and Aβ_1-42-injected groups. More specifically, the ratio of the frontal EEG beta and alpha power (rFBA) was significantly affected by the intrahippocampal injection of Aβ_1-42 (p ​< ​0.0001). Also, we observed that rFBA was negatively and strongly correlated with hippocampal Aβ_1-42 peptide levels (r ​= ​−0.781, p ​< ​0.0001).

Conclusion

Our findings indicate that spontaneous frontal EEG beta and alpha activity were significantly affected by the intrahippocampal injection of Aβ_1-42. However, the results suggest that the power ratios of these bands are more sensitive to the hippocampal amyloid pathology. As such, it is proposed that the rFBA may be a more effective biomarker for diagnosing hippocampal pathology induced by Aβ_1-42.

Background

The COVID-19 pandemic exerted significant impacts on public health and global economy. Research efforts to develop vaccines at warp speed against SARS-CoV-2 led to novel mRNA, viral vectored, and inactivated vaccines being administered. The current COVID-19 vaccines incorporate the full S protein of the SARS-CoV-2 Wuhan strain but rapidly emerging variants of concern (VOCs) have led to significant reductions in protective efficacies. There is an urgent need to develop next-generation vaccines which could effectively prevent COVID-19.

Methods

PubMed and Google Scholar were systematically reviewed for peer-reviewed papers up to January 2023.

Results

A promising solution to the problem of emerging variants is a DNA vaccine platform since it can be easily modified. Besides expressing whole protein antigens, DNA vaccines can also be constructed to include specific nucleotide genes encoding highly conserved and immunogenic epitopes from the S protein as well as from other structural/non-structural proteins to develop effective vaccines against VOCs. DNA vaccines are associated with low transfection efficiencies which could be enhanced by chemical, genetic, and molecular adjuvants as well as delivery systems.

Conclusions

The DNA vaccine platform offers a promising solution to the design of effective vaccines. The challenge of limited immunogenicity in humans might be solved through the use of genetic modifications such as the addition of nuclear localization signal (NLS) peptide gene, strong promoters, MARs, introns, TLR agonists, CD40L, and the development of appropriate delivery systems utilizing nanoparticles to increase uptake by APCs in enhancing the induction of potent immune responses.

Purpose

Lung cancer (LC) is a common malignancy worldwide. A great number of circular RNAs (circRNAs) have been identified that serve crucial roles in cancer development. Extracellular vesicles (EVs) and their contents have been shown to be biomarkers for the diagnosis and prognosis of LC. Thus, we intended to clarify the functional role of EVs-derived circRNA homology domain interacting protein kinase 3 (EVs-circHIPK3) and its underlying mechanism of action.

Material and methods

Bioinformatics analysis was performed to validate the potential of partially circulating HIPK3 in LC diagnosis. EVs were isolated by polyethylene glycol (PEG) precipitation from plasma of 52 LC patients and 30 healthy controls. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was employed to evaluate the expressions of candidate circRNAs (circHIPK3) and microRNA-637 (miR-637, a target of circHIPK3).

Results

CircHIPK3 is significantly up-regulated in LC, while miR-637 expression is significantly reduced (p ​< ​0.05). Receiver operating characteristic (ROC) curve analysis, based on the expression of EVs-circHIPK3, allowed us to distinguish LC from healthy controls (area under the curve, AUC 0.897).

Conclusions

Taken together, our study shows that EV-derived circHIPK3 can serve as a promising biomarker for LC patient diagnosis. However, the downstream mRNA of the circHIPK3/miR-637 axis requires further exploration to enrich our understanding of circHIPK3's mechanism in LC.

Purpose

Coronavirus disease 2019 (COVID-19) is linked with major coagulation disorders, especially higher risk of developing pulmonary embolism (PE). Our study summarizes COVID-19 patients’ management with concomitant PE during the first weeks of pandemic and underlines the importance of D-dimer concentration assessment at admission in terms of prognosis.

Material and methods

Study group consisted of 107 outpatients (mean age 68.91 ​± ​12.83 years) admitted to the Temporary COVID-19 Hospital in Bialystok, Poland with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and suspicion of PE based on elevated D-dimer concentration (>500 ​μg/l) and/or low saturation rate (<90%). The clinical follow-up lasted 6 months. Death or re-hospitalization were used as composite clinical endpoint (CEP).

Results

Cumulative incidence of PE was 62.3% (73/107 patients). Most of the patients were in the intermediate PE risk group according to the pulmonary embolism severity index (PESI) score. The mean total computed tomography (CT) lung involvement of COVID-19 findings was 48.42 ​± ​27.71%. Neither D-dimers nor NT-proBNP concentrations correlated significantly with the percentage of lung abnormalities in CT. Patients with baseline D-dimer concentration higher than 1429 ​μg/l had worse prognosis in 6-months observation, log-rank test, p ​= ​0.009.

Conclusions

Ongoing SARS-CoV-2 infection along with massive involvement of lung tissue and concomitant thrombi in pulmonary arteries are challenging for physicians. It seems that simple D-dimer concentration assessment at admission may be a helpful tool not only to predict PE but also to estimate the long-term prognosis.

Periodontitis is an infectious disease characterized by the inflammatory destruction of the tooth supporting tissues. In multi-rooted teeth, this process leads to periodontal destruction within furcations creating defects demanding in terms of treatment. Regeneration of class II furcation involvement, although possible, is considered an unpredictable procedure, especially in terms of the bone fill. The interest in wound healing improvement by additional use of autologous concentrates of growth factors remains high in many fields of dentistry. Platelet-rich fibrin (PRF) is a second-generation platelet concentrate and biomaterial. PRF forms a solid fibrin matrix, which is slowly remodeled comparable to the natural blood clot. Its utilization is associated with release of growth factors and glycoproteins over a long period of time. PRF activates alkaline phosphates, which show osteoblastic activity and this activation influences the bone formation.

The aim of this review of randomized controlled trials (RCTs) was to evaluate the adjunctive use of platelet-rich fibrin in surgical treatment of furcation defects.