The role of microbiomes in gastrointestinal cancers: new insights

Gastrointestinal (GI) cancers constitute more than 33% of new cancer cases worldwide and pose a considerable burden on public health. There exists a growing body of evidence that has systematically recorded an upward trajectory in GI malignancies within the last 5 to 10 years, thus presenting a formidable menace to the health of the human population. The perturbations in GI microbiota may have a noteworthy influence on the advancement of GI cancers; however, the precise mechanisms behind this association are still not comprehensively understood. Some bacteria have been observed to support cancer development, while others seem to provide a safeguard against it. Recent studies have indicated that alterations in the composition and abundance of microbiomes could be associated with the progression of various GI cancers, such as colorectal, gastric, hepatic, and esophageal cancers. Within this comprehensive analysis, we examine the significance of microbiomes, particularly those located in the intestines, in GI cancers. Furthermore, we explore the impact of microbiomes on various treatment modalities for GI cancer, including chemotherapy, immunotherapy, and radiotherapy. Additionally, we delve into the intricate mechanisms through which intestinal microbes influence the efficacy of GI cancer treatments

Regenerative potential of mesenchymal stromal cells in wound healing: unveiling the influence of normoxic and hypoxic environments

The innate and adaptive immune systems rely on the skin for various purposes, serving as the primary defense against harmful environmental elements. However, skin lesions may lead to undesirable consequences such as scarring, accelerated skin aging, functional impairment, and psychological effects over time. The rising popularity of mesenchymal stromal cells (MSCs) for skin wound treatment is due to their potential as a promising therapeutic option. MSCs offer advantages in terms of differentiation capacity, accessibility, low immunogenicity, and their central role in natural wound-healing processes. To accelerate the healing process, MSCs promote cell migration, angiogenesis, epithelialization, and granulation tissue development. Oxygen plays a critical role in the formation and expansion of mammalian cells. The term “normoxia” refers to the usual oxygen levels, defined at 20.21 percent oxygen (160 mm of mercury), while “hypoxia” denotes oxygen levels of 2.91 percent or less. Notably, the ambient O2 content (20%) in the lab significantly differs from the 2%–9% O2 concentration in their natural habitat. Oxygen regulation of hypoxia-inducible factor-1 (HIF-1) mediated expression of multiple genes plays a crucial role in sustaining stem cell destiny concerning proliferation and differentiation. This study aims to elucidate the impact of normoxia and hypoxia on MSC biology and draw comparisons between the two. The findings suggest that expanding MSC-based regenerative treatments in a hypoxic environment can enhance their growth kinetics, genetic stability, and expression of chemokine receptors, ultimately increasing their effectiveness

Mesenchymal stem cell therapy for non-healing diabetic foot ulcer infection: New insight

Diabetic foot ulcer (DFU) is considered the most catastrophic complication of diabetes mellitus (DM), leading to repeated hospitalizations, infection, gangrene, and finally amputation of the limb. In patients suffering from diabetes mellitus, the wound-healing process is impaired due to various factors such as endothelial dysfunction and synthesis of advanced glycation end-products, hence, conventional therapeutic interventions might not be effective. With increasing therapeutic applications of mesenchymal stem cells (MSCs) in recent years, their potential as a method for improving the wound-healing process has gained remarkable attention. In this field, mesenchymal stem cells exert their beneficial effects through immunomodulation, differentiation into the essential cells at the site of ulcers, and promoting angiogenesis, among others. In this article, we review cellular and molecular pathways through which mesenchymal stem cell therapy reinforces the healing process in non-healing Diabetic foot ulcers

Detection of carbapenem resistance and virulence genes among Acinetobacter baumannii isolated from hospital environments in center of Iran

Carbapenem-resistant Acinetobacter baumannii are the top urgent antibiotic resistance threat in the world. The aims of this study were the determination of carbapenem-resistant genes and virulence genes among isolates from hospital environments. In this study, A. baumannii isolated from hospital environments and evaluated its antibiotic resistance, virulence factors, and resistance genes. Of 258 samples, 58 showed growth of the target organism. Antibiotic susceptibility test results considered all the A. baumannii to be multidrug-resistant isolates with the highest resistance being 36.2% to ciprofloxacin; while the most effective antibiotics with 98.3% susceptibility was piperacillin-tazobactam. Of these 58 hospital environment isolates, 18 isolates were positive for Metallo beta-lactamase. Overall, 65% of the isolates from hospital environments had many virulence factors. PCR assays demonstrated the highest and lowest positive results in csgA and cvaC gene among hospital environment isolates. Results indicate that the determination of carbapenem-resistant genes and virulence genes among isolates from hospital environments is very important

Application of hypoxia-mesenchymal stem cells in treatment of anaerobic bacterial wound infection: wound healing and infection recovery

Mesenchymal stromal cells, commonly referred to as MSCs, are a type of multipotent stem cells that are typically extracted from adipose tissue and bone marrow. In the field of tissue engineering and regenerative medicine, MSCs and their exosomes have emerged as revolutionary tools. Researchers are now devoting greater attention to MSCs because of their ability to generate skin cells like fibroblasts and keratinocytes, as well as their distinctive potential to decrease inflammation and emit pro-angiogenic molecules at the site of wounds. More recent investigations revealed that MSCs can exert numerous direct and indirect antimicrobial effects that are immunologically mediated. Collectively, these antimicrobial properties can remove bacterial infections when the MSCs are delivered in a therapeutic setting. Regardless of the positive therapeutic potential of MSCs for a multitude of conditions, transplanted MSC cell retention continues to be a major challenge. Since MSCs are typically administered into naturally hypoxic tissues, understanding the impact of hypoxia on the functioning of MSCs is crucial. Hypoxia has been postulated to be among the factors determining the differentiation of MSCs, resulting in the production of inflammatory cytokines throughout the process of tissue regeneration and wound repair. This has opened new horizons in developing MSC-based systems as a potent therapeutic tool in oxygen-deprived regions, including anaerobic wound infection sites. This review sheds light on the role of hypoxia-MSCs in the treatment of anaerobic bacterial wound infection in terms of both their regenerative and antimicrobial activities

Automated deep learning-based segmentation of COVID-19 lesions from chest computed tomography images

Purpose: The novel coronavirus COVID-19, which spread globally in late December 2019, is a global health crisis. Chest computed tomography (CT) has played a pivotal role in providing useful information for clinicians to detect COVID-19. However, segmenting COVID-19-infected regions from chest CT results is challenging. Therefore, it is desirable to develop an efficient tool for automated segmentation of COVID-19 lesions using chest CT. Hence, we aimed to propose 2D deep-learning algorithms to automatically segment COVID-19-infected regions from chest CT slices and evaluate their performance. Material and methods: Herein, 3 known deep learning networks: U-Net, U-Net++, and Res-Unet, were trained from scratch for automated segmenting of COVID-19 lesions using chest CT images. The dataset consists of 20 labelled COVID-19 chest CT volumes. A total of 2112 images were used. The dataset was split into 80% for training and validation and 20% for testing the proposed models. Segmentation performance was assessed using Dice similarity coefficient, average symmetric surface distance (ASSD), mean absolute error (MAE), sensitivity, specificity, and precision. Results: All proposed models achieved good performance for COVID-19 lesion segmentation. Compared with Res-Unet, the U-Net and U-Net++ models provided better results, with a mean Dice value of 85.0%. Compared with all models, U-Net gained the highest segmentation performance, with 86.0% sensitivity and 2.22 mm ASSD. The U-Net model obtained 1%, 2%, and 0.66 mm improvement over the Res-Unet model in the Dice, sensitivity, and ASSD, respectively. Compared with Res-Unet, U-Net++ achieved 1%, 2%, 0.1 mm, and 0.23 mm improvement in the Dice, sensitivity, ASSD, and MAE, respectively. Conclusions: Our data indicated that the proposed models achieve an average Dice value greater than 84.0%. Two-dimensional deep learning models were able to accurately segment COVID-19 lesions from chest CT images, assisting the radiologists in faster screening and quantification of the lesion regions for further treatment. Nevertheless, further studies will be required to evaluate the clinical performance and robustness of the proposed models for COVID-19 semantic segmentation

A historical literature review on the role of posterior axillary boost field in the axillary lymph node coverage and development of lymphedema following regional nodal irradiation in breast cancer

To elucidate whether (1) a posterior axillary boost (PAB) field is an optimal method to target axillary lymph nodes (LNs); and (2) the addition of a PAB increases the incidence of lymphedema, a systematic review was undertaken. A literature search was performed in the PubMed database. A total of 16 studies were evaluated. There were no randomized studies. Seven articles have investigated dosimetric aspects of a PAB. The remaining 9 articles have determined the effect of a PAB field on the risk of lymphedema. Only 2 of 9 articles have prospectively reported the impact of a PAB on the risk of lymphedema development. There are conflicting reports on the necessity of a PAB. The PAB field provides a good coverage of level I/II axillary LNs because these nodes are usually at a greater depth. The main concern regarding a PAB is that it produces a hot spot in the anterior region of the axilla. Planning studies optimized a traditional PAB field. Prospective studies and the vast majority of retrospective studies have reported the use of a PAB field does not result in increasing the risk of lymphedema development over supraclavicular-only field. The controversies in the incidence of lymphedema suggest that field design may be more important than field arrangement. A key factor regarding the use of a PAB is the depth of axillary LNs. The PAB field should not be used unless there is an absolute indication for its application. Clinicians should weigh lymphedema risk in individual patients against the limited benefit of a PAB, in particular after axillary dissection. The testing of the inclusion of upper arm lymphatics in the regional LN irradiation target volume, and universal methodology measuring lymphedema are all areas for possible future studies

The role of long non-coding RNAs and circular RNAs in cervical cancer: modulating miRNA function

Cervical cancer (CC) is a primary global health concern, ranking as the fourth leading cause of cancer-related death in women. Despite advancements in prognosis, long-term outcomes remained poor. Beyond HPV, cofactors like dietary deficiencies, immunosuppression, hormonal contraceptives, co-infections, and genetic variations are involved in CC progression. The pathogenesis of various diseases, including cancer, has brought to light the critical regulatory roles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). The aberrant expression of these miRNAs, lncRNAs, and circRNAs plays a pivotal role in the initiation and progression of CC. This review provides a comprehensive summary of the recent literature regarding the involvement of lncRNAs and circRNAs in modulating miRNA functions in cervical neoplasia and metastasis. Studies have shown that lncRNAs and circRNAs hold great potential as therapeutic agents and innovative biomarkers in CC. However, more clinical research is needed to advance our understanding of the therapeutic benefits of circRNAs and lncRNAs in CC

Determination of CagA EPIYA motif in Helicobacter pylori strains isolated from patients with digestive disorder

This study was conducted to identify patterns of cagA EPIYA motifs in H. pylori strains isolated from patients with gastrointestinal diseases in Hospitals of Shahrekord, and investigate the association between these biomarkers and clinical outcomes of gastrointestinal diseases due to H. pylori. In this study, 253 patients with gastrointestinal diseases were studied within 1395-1396. Histopathological investigations and urease test showed that 207 isolates were H. pylori-positive. Then, screening using a molecular technique, PCR, confirmed that 159 isolates had cagA. Finally, the pattern and prevalence of the motifs were determined by PCR and identified a number of motifs were sequenced. Results of this study showed that the pattern of motifs was as follows: ABC (140 isolates) (93/7%), ABCC (6 isolates) (3/77%), ABCCC (4 isolates) (2/5%), AB (7 isolates) (4/4%), AC (1 isolate) (0/6%), and BC (1 isolate) (0/6%). Sequencing results showed the presence of changed EPIYA motif in some isolates. CM motif sequence was also seen in all isolates. In this study, no significant association was seen between the prevalence rate of different patterns and clinical symptoms (p = 0.71). There is a slight association between the presence of ABC motifs and the type of digestive disorder (p = 0.056). Results indicated that ABC was the most frequently seen pattern however, in such that positive cases of ABC motifs were more common in gastritis. All isolates had kinase phosphorylation region, and the observed pattern in this region was a generally western type (ABC). Keywords:Microbiology; Immunology; Genetics; Molecular biology; Cancer research; Diet; Public health; Gastrointestinal system; Infectious disease; Helicobacter pylori; CagA motif; EPIYA; Gastric cance

Recent advances in different interactions between toll-like receptors and hepatitis B infection: a review

Hepatitis B virus (HBV) B infections remain a primary global health concern. The immunopathology of the infection, specifically the interactions between HBV and the host immune system, remains somewhat unknown. It has been discovered that innate immune reactions are vital in eliminating HBV. Toll-like receptors (TLRs) are an essential category of proteins that detect pathogen-associated molecular patterns (PAMPs). They begin pathways of intracellular signals to stimulate pro-inflammatory and anti-inflammatory cytokines, thus forming adaptive immune reactions. HBV TLRs include TLR2, TLR3, TLR4, TLR7 and TLR9. Each TLR has its particular molecule to recognize; various TLRs impact HBV and play distinct roles in the pathogenesis of the disease. TLR gene polymorphisms may have an advantageous or disadvantageous efficacy on HBV infection, and some single nucleotide polymorphisms (SNPs) can influence the progression or prognosis of infection. Additionally, it has been discovered that similar SNPs in TLR genes might have varied effects on distinct populations due to stress, diet, and external physical variables. In addition, activation of TLR-interceded signaling pathways could suppress HBV replication and increase HBV-particular T-cell and B-cell reactions. By identifying these associated polymorphisms, we can efficiently advance the immune efficacy of vaccines. Additionally, this will enhance our capability to forecast the danger of HBV infection or the threat of dependent liver disease development via several TLR SNPs, thus playing a role in the inhibition, monitoring, and even treatment guidance for HBV infection. This review will show TLR polymorphisms, their influence on TLR signaling, and their associations with HBV diseases