Abstract

Liver fibrosis is an intrahepatic chronic damage repair response caused by various reasons such as alcoholic liver, fatty liver, viral hepatitis, autoimmune diseases, etc., and is closely related to the progression of liver disease. Currently, the mechanisms of liver fibrosis and its treatment are hot research topics in the field of liver disease remedy. Mesenchymal stem cells (MSCs) are a class of adult stem cells with self-renewal and multidirectional differentiation potential, which can ameliorate fibrosis through hepatic-directed differentiation, paracrine effects, and immunomodulation. However, the low inner-liver colonization rate, low survival rate, and short duration of intervention after stem cell transplantation have limited their wide clinical application. With the intensive research on liver fibrosis worldwide, it has been found that MSCs and MSCs-derived exosomes combined with drugs have shown better intervention efficiency than utilization of MSCs alone in many animal models of liver fibrosis. In this paper, we review the interventional effects and mechanisms of mesenchymal stem cells and their exosomes combined with drugs to alleviate hepatic fibrosis in vivo in animal models in recent years, which will provide new ideas to improve the efficacy of mesenchymal stem cells and their exosomes in treating hepatic fibrosis in the clinic.

Introduction

The liver is mainly composed of hepatocytes, hepatic stellate cells (HSCs), and liver sinusoidal endothelial cells (LSECs) that perform a comprehensive range of hepatic functions, such as detoxification, bile acid synthesis, and participation in various metabolic processes. However, a variety of stimuli, such as alcohol, drugs, inflammation, or cholestasis, often cause damage to hepatocytes resulting in abnormal liver function and a series of pathophysiologic changes [1] . Liver fibrosis is a common intermediate pathological process of various chronic liver diseases, which is mainly manifested by diffuse excessive deposition of extracellular matrix, leading to abnormal changes in liver tissue structure and affecting the normal physiological functions of liver severely [2] . Clinically, if liver fibrosis is not effectively reversed or curbed, it will progress to irreversible cirrhosis, hepatocellular carcinoma, and other end-stage liver diseases, eventually, leading to the death of patients [3] . Therefore, finding effective therapeutic strategies to ameliorate liver fibrosis in patients is of great importance in preventing the development of end-stage liver diseases.

In the clinical setting, liver transplantation is mostly used for the treatment of end-stage liver diseases, but liver transplantation cannot be widely used due to the defects of extremely rare donors, high cost, rejection, etc [4] . Currently, mesenchymal stem cells for the treatment of liver disease have become a hot spot in the field of biomedicine. As the intermediate pathological process of end-stage liver disease, mesenchymal stem cells can effectively ameliorate hepatic fibrosis through hepatogenic differentiation, immunomodulation, paracrine effects, and other mechanisms [5] . However, it has been reported that MSCs transplanted in the body may have some disadvantages such as low inner-liver colonization and short duration of intervention, which affect their therapeutic efficacy [6] . Nowadays, an increasing number of researchers have demonstrated in animal models of liver fibrosis that the combination of MSCs with drugs can boost the therapeutic effect of MSCs in the treatment of liver fibrosis by promoting the homing of MSCs, differentiating them into functional hepatocyte-like cells, improving the microenvironment, inhibiting the activation of HSCs, and modulating the signaling pathway, and so on. In addition, MSCs-derived extracellular vesicles with the advantages of higher penetrability and lower carcinogenicity also effectively ameliorate liver fibrosis with ultimate safety. What’s more, nanoscale intracellular vesicles can also be used as carriers of natural drugs for drug delivery. This provides new ideas to solve the poor efficiency of MSCs in the treatment of liver fibrosis in the clinic.

Discussion and outlook

Liver fibrosis, as an intermediate pathological process from chronic liver disease to cirrhosis and hepatocellular carcinoma, has become a research hotspot for the treatment of liver diseases due to its reversible properties. However, there is no very effective means to treat liver fibrosis in clinical practice. MSCs, as a kind of pluripotent stem cells, have no ethical issues and wide sources compared with liver transplantation and hepatocyte transplantation, which have attracted much attention in animal experiments and clinical studies of cell transplantation for the treatment of liver fibrosis. Unfortunately, MSCs confront with the challenges such as in vivo microenvironment inadaptation and attenuation of inflammatory response ability after isolation and culture in vitro [45] , which ultimately leads to a low colonization rate and short duration of intervention after transplantation of MSCs into the liver [6] . Therefore, it has not been widely used in clinical practice.

Abstract

Oral cavity stem cells (OCSCs) have been the focus of intense scientific efforts due to their accessibility and stem cell properties. The present work aims to compare the different characteristics of 6 types of dental stem cells derived from the oral cavity: dental pulp stem cells (DPSC), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSC), stem cells from the apical papilla (SCAP), bone marrow mesenchymal stem cells (BMSC), and gingival mesenchymal stem cells (GMSC). Using immunofluorescence and real-time polymerase chain reaction techniques, we analysed the cells for stem cell, differentiation, adhesion, and extracellular matrix markers; the ability to proliferate in vitro; and multilineage differentiation potential. Markers such as vimentin, CD44, alkaline phosphatase, CD146, CD271, CD49f, Oct 3/4, Sox 9, FGF7, nestin, and BMP4 showed significant differences in expression levels, highlighting the heterogeneity and unique characteristics of each cell type. At the same time, we confirmed that all cell types successfully differentiated into osteogenic, chondrogenic, or adipose lineages, with different readiness. In conclusion, our study reveals the distinct properties and potential applications of various dental-derived stem cells. These findings contribute to a deeper understanding of OCSCs and their significance in future clinical applications.

Introduction

Bone marrow mesenchymal stem cells (BMSCs) exhibit high proliferation ability and multilineage differentiation potential. They were the first mesenchymal stem cells (MSCs) to be described, isolated from adults’ bone marrow aspirate.1 They have been extensively researched in human and animal model systems using in vivo and in vitro cell cultures. Further, they have bridged the divide and are integrated into various trials for clinical applications, with mixed success.2,3 BMSCs are not easily accessible, and an invasive procedure is required. Therefore, further research in the field, aiming at identifying alternative stem cell sources, has led to the discovery of oral cavity stem cells (OCSCs).

Currently, several different types of OCSCs are well known, including dental pulp stem cells (DPSC), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSC), stem cells from the apical papilla (SCAP), dental follicle stem cells (DFSC), and gingival mesenchymal stem cells (GMSC).

Conclusions

This analysis of oral cavity–derived stem cells has exposed distinct and specific expression patterns of surface markers, ECM components, ECM remodelling enzymes, collagen genes, integrins, and differentiation potential. These findings may provide insights into the functional properties of these cell populations. Оur study aims to uncover the nuanced characteristics specific to each distinct cell type. Through experimentation and analysis, we anticipate to not only understand their individual functionalities but also gain deeper insights into their collective behaviour. Understanding both their shared characteristics and distinct attributes is an important step in using their regenerative potential in various tissue repair and regeneration contexts, thereby advancing the field of regenerative medicine and tissue engineering. By contributing meaningfully to the advancement of knowledge in regenerative medicine and tissue engineering, we aspire to pave the way for transformative breakthroughs in health care.

Abstract

PDHα1 gene encodes catalytic subunit PDHE1α of pyruvate dehydrogenase (PDH) complex. Based on previous studies, it is hypothesized that inhibition of PDH activity prevents the entry of glycolytic pyruvate into TCA cycle, while promotes fatty acid oxidation and reduces liver triglyceride (TG) level, thereby alleviating nonalcoholic fatty liver disease (NAFLD). In this study, an in vitro model for NAFLD was established with medical fat emulsion; the most effective siRNA for PDHα1 gene was screened out by qPCR technology; the alterations in metabolism of glucose and lipid, and structure & function of mitochondria in the NAFLD cells were primarily evaluated after transfecting PDHα1 siRNA. As the results showed, after inhibiting the expression of PDHα1 gene, glucose level in culture medium was time-dependently increased, and LDH activity in the cells was moderately elevated after 24 h of transfection and then returned to the normal level after 48 h; intracellular TG level was decreased while LPS activity was increased in a time-dependent manner; no significant change in mitochondrial structure was observed with or without siRNA transfection, and ATP content was obviously reduced after 24 h of transfection, followed by restoration after 48 h. It can be concluded that inhibiting PDHα1 gene in fatty liver cells enhances lipid degradation, and represses the utilization of glucose to an extent, thus reducing TG level without impacting energy generation required for cell survival.

Introduction

Nonalcoholic fatty liver disease (NAFLD) is a continuous spectrum of diseases characterized by excessive deposition of fat in the liver accompanied with diffuse hepatic cell bullous steatosis caused by the factors other than alcohol and other known liver injury-related factors (Farrell et al., 2007, Targher and Byrne, 2017). In turn, hepatic steatosis further aggravates liver metabolic disorders, or even develops into liver fibrosis and cirrhosis, exacerbating liver damage if not given proper treatment (Monteillet et al., 2018).

Nowadays, it has been widely accepted that intrahepatic lipid accumulation caused by various factors (excessive liver fat synthesis, insulin resistance, inflammation, mitochondrial dysfunction, gut microbiota and adipokines), together with the increased de novo fatty acid synthesis, the reduced fatty acid oxidation (FAO) and the blocked liver lipid efflux ultimately cause the occurrence of fatty liver disease (Ratziu et al., 2016, Matsumoto et al., 2018). Obviously, the formation of fatty liver is closely related with the abnormality of lipid metabolism. Accordingly, how to improve the degradation and transportation of intrahepatic lipid is of great significance in preventing the occurrence of fatty liver. It is noteworthy that mitochondria, also called powerhouses of the cells, play an important role in the regulation of fat metabolism and inflammatory response (Ni et al., 2015). As an example, it has been found that adding MitoQ, one mitochondrial-targeted antioxidant, could strongly rescue mitochondrial function and attenuate the development of fatty liver disease by decreasing pathogenic alterations of cardiolipin content, an unique mitochondrial phospholipid playing a key role in mitochondrial bioenergetics (Fouret et al., 2015).

Conclusions

Based on above findings, inhibiting PDHα1 gene expression could attenuate glucose utilization by the cells, while facilitate lipid degradation which was mainly reflected by the elevated glucose level in the medium and the increased LPS activity, respectively; whereas the cellular energy produced by lipid degradation after interfering the expression of this gene might be not enough to compensate for the decrease of ATP level caused by the reduced glycolysis, which might be the reason for the short-time decrease of energy production.

Abstract

1. Introduction

2. Methods

3. Results

4. Discussion

5. Conclusion

Author contribution

Registration of research studies

Acknowledgement

References

Abstract

Background
Iron deficiency anemia (IDA) is a common complication of inflammatory bowel disease (IBD) in pregnant women. Although studies have shown that certain maternal autoimmune diseases are associated with attention deficit hyperactivity disorder (ADHD) in children, no studies have found a relationship specifically between and IDA in pregnant women with IBD and ADHD in their children. This review aims identify a relationship between maternal Crohn’s disease (CD) with IDA and ADHD in children.

Materials and methods
A review of existing literature was conducted using PubMed to search for articles on pregnant women with CD and IDA and children with ADHD. The studies included nested case-control studies, cohort studies, cross-sectional studies, case-control studies, and literature reviews published from 2012 to 2021.

Results
Among 876 articles generated, 11 studies were chosen for this review. Inclusion criteria consisted of no animal studies, meta-analysis or systematic reviews followed by ADHD related topics and maternal CD and IDA. The findings show that ADHD in progeny may be attributed to maternal CD. Although no studies have shown that IDA in mothers with CD is related to ADHD in offspring, several studies have shown a positive correlation between maternal IDA and ADHD in offspring. Some studies suggest inflammation in IBD during pregnancy can inflame the central nervous system, leading to ADHD in offspring.

Conclusion
IDA is a prevalent complication in CD, and inadequate iron levels are associated with neurodevelopmental problems, such as ADHD. Iron therapy for pregnant mothers diagnosed with CD is suggested to prevent ADHD in offspring.

Introduction

     Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood, affecting approximately 8.4% of US children between 2 and 17 years of age [1,2]. Symptoms of ADHD include losing items, disorganization, an inability to pay attention and concentrate, forgetting things quickly, and struggling to complete activities [2]. Evidence links the disorder’s etiology to multiple factors, including genetics, environmental aspects and certain maternal autoimmune disorders such as psoriasis, rheumatoid arthritis, asthma and others [3,4].

     Although studies have shown an association between certain maternal autoimmune diseases and ADHD in offspring, not much is known about how maternal inflammatory bowel diseases (IBDs), such as Crohn’s disease (CD), affect neurodevelopment in progeny. It was recently estimated that approximately 1.5 million people have IBD, including ulcerative colitis, in the United States, causing considerable health and financial loss every year [5]. In most cases, the development of anemia is caused by iron deficiency, and results have shown that nearly 27% of people treated for CD have iron deficiency anemia (IDA) [4]. Furthermore, women with CD are at higher risk of anemia than men with CD possibly due to blood loss during menstruations [6].

Results

     This review attempted to answer the question, “Is there a relationship between IDA in maternal CD and ADHD?” The search resulted in 11 studies (Appendix 1). These studies include 2 literature reviews [7,8], 4 cohort studies, 3 cross-sectional studies, 1 case-control study, and 1 nested case-control study.

3.1. Case-control studies

    We found one case-control study [9] assessing the link between iron deficiency and ADHD in children (n = 630) from 5 to 18 years of age in Qatar. The findings indicated that mean ferritin levels were significantly lower in children with ADHD than in the control group (36.26 ± 5.93, 38.19 ± 5.61, respectively; p ≤ .01). Ferritin levels in children without ADHD were within the normal range. The researchers suggested that iron deficiency is linked to cognitive impairment, instability in psychomotor aspects in children, and difficulties in learning because of impairment within the central dopaminergic pathway. In summary, the study found that iron deficiency was strongly associated with ADHD symptoms, and these findings revealed the need for careful examination and possibly early intervention of iron supplementation in affected children to reduce the risk of ADHD.

 Keywords

Methods

Results

Discussion

Supplementary Data

References

Article Info

Figures

Tables

Related Articles

Objective
To use next generation sequencing (NGS) technology to identify undiagnosed, monogenic diseases in a cohort of children who suffered from acute liver failure (ALF) without an identifiable etiology.

Study design
We identified 148 under 10 years of age admitted to King’s College Hospital, London, with ALF of indeterminate etiology between 2000 and 2018. A custom NGS panel of 64 candidate genes known to cause ALF and/or metabolic liver disease was constructed. Targeted sequencing was carried out on 41 children in whom DNA samples were available. Trio exome sequencing was performed on 4 children admitted during 2019. A comparison of the clinical characteristics of those identified with biallelic variants against those without biallelic variants was then made.

Results
Homozygous and compound heterozygous variants were identified in 8 out of 41 children (20%) and 4 out of 4 children (100%) in whom targeted and exome sequencing were carried out, respectively. The genes involved were NBAS (3 children); DLD (2 children); and CPT1A, FAH, LARS1, MPV17, NPC1, POLG, SUCLG1, and TWINK (1 each). The 12 children who were identified with biallelic variants were younger at presentation and more likely to die in comparison with those who did not: median age at presentation of 3 months and 30 months and survival rate 75% and 97%, respectively.

Conclusions
NGS was successful in identifying several specific etiologies of ALF. Variants in NBAS and mitochondrial DNA maintenance genes were the most common findings. In the future, a rapid sequencing NGS workflow could help in reaching a timely diagnosis and facilitate clinical decision making in children with ALF.

Historically, reports from Europe and North America of children with acute liver failure (ALF) identified infectious, metabolic, and drug-related etiologies but the cause remained unexplained in approximately one-half of all cases.1,  2,  3 Despite the progress made over the last 40 years the rate of indeterminate cases remains ~30%.4 Therefore, challenges remain when evaluating the indeterminate cohort who have a lower chance of spontaneous survival, and higher rates of liver transplantation and death when compared with other diagnostic categories.4,5

The rapid increase in the use of next generation sequencing (NGS) since its advent in 2004 has transformed the way children with rare diseases such as ALF are evaluated. This is particularly relevant when considering the more recently identified monogenic disorders such as those caused by variants in NBAS,6 SCYL1,7 and RINT1.8 Therefore, the purpose of this study was to use NGS technology to identify undiagnosed, monogenic diseases in children who received a diagnosis of indeterminate ALF and to gain insight into how this information may assist us in making therapeutic decisions for affected children in the future.

1- Introduction

2- Materials and methods

3- Results

4- Discussion

References

Abstract

Drug resistance is a big problem in cancer treatment and one of the most prominent mechanisms underlain is overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1, ABCC1 and ABCG2. Inhibition of ABC transporters is an important approach to overcome drug resistance. The inositol-requiring enzyme 1α (IRE1α), an arm of unfolded protein response (UPR), splices XBP1 mRNA to generate an active transcription factor XBP1s. UPR is implicated in drug resistance. However, the underlying mechanism is unclear. We found that the anticancer drugs such as 5-fluorouracil (5-FU) activated the IRE1α-XBP1 pathway to induce the expression of ABCB1, ABCC1 and ABCG2 in colon cancer cells. Inhibition of IRE1α RNase activity with small molecule 4μ8c suppressed the drug-induced expression of these ABC transporters and sensitized 5-FU-resistant colon cancer cells to drug treatment. In vivo xenograft assay indicates that administration of 4μ8C substantially enhanced the efficacy of 5-FU chemotherapy on 5-FU-resistant colon cancer cells. These results suggest that IRE1α-targeting might be a strategy to cope with drug resistance of colon cancer.

Introduction

Cancers have the ability to develop resistance to chemotherapy, and the increasing prevalence of these drug resistant cancers necessitates further research and treatment development. Multidrug resistance is a phenomenon by which, after exposure to a chemotherapeutic agent, cancer cells develop resistance, and simultaneous cross-resistance, to a wide range of functionally and structurally unrelated chemotherapeutic drugs (1, 2). Intrinsic or acquired multidrug resistance is one of the main reasons for chemotherapy failure, leading to the recurrence of malignant tumors and ultimately, patient relapse or death (3). A variety of mechanisms have been attributed to multidrug resistance, such as enhanced drug efflux, increased DNA damage repair, reduced apoptosis, elevated autophagy, and/or altered drug metabolism (4-6). Previous studies have confirmed that multidrug resistance both in cancer cell lines and human tumor tissues is most often associated with the overexpression of the ATP-binding cassette (ABC) transporters (4, 7, 8). These ABC transporters are efflux pumps that transport various structurally unrelated and potentially dangerous substances out of the cells. They hydrolyze ATP for energy and actively pump drug components out of cells, leading to drug resistance. In these transporters, ABCB1 (also known as MDR1 or P-gp), ABCC1 (MRP1) and ABCG2 (BCRP1) play an important role in drug resistance in vivo (4, 7). Developing inhibitors of ABC transporters is an important approach to overcoming drug resistance. Extensive efforts have been made to develop inhibitors targeting ABC transporters, particularly ABCB1. However, no such agents have been developed successfully as was initially hoped.

1- Introduction

2- Materials and methods

3- Results

4- Discussion

References

Abstract

No data are available on whether a diet deficient of the essential fatty acids is able to modulate tissue levels of endocannabinoids and congeners. Male rats fed for 12 weeks a diet deficient of essential fatty acids, palmitic and oleic acids (EFAD), replaced with saturated fatty acids (SAFA), showed lowered n-3 and n-6 PUFAs levels in plasma, liver and adipose tissue, with concomitant steep increase of oleic and mead acids, while in hypothalamus no changes in PUFA concentration were detected and only palmitoleic acid was found increased. We found a reduction of anandamide and palmitoylethanolamide in liver and brain, while oleoylethanolamide increased significantly in liver and adipose tissue, associated to a 50 % body weight decrease. Changes in N-acylethanolamide profile may contribute to body weight reduction distinctive of EFA deficiency.

Introduction

Several lines of evidence show that dietary fatty acids may influence endocannabinoids (ECs) and their congeners tissue profiles in vitro [1] and in vivo [2]. Most of the studies aimed at evaluating whether changes in arachidonic acid (ARA, 20:4n-6) tissue phospholipids (PL) content were able to modulate the main ECs anandamide (AEA) and 2-arachidonoylglycerol (2-AG) [3]. Two major strategies have been described in the literature, reduction of ARA by increasing dietary n-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs), i.e. eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) [4], or increasing it by feeding ARA precursor, linoleic acid (LA, 18:2n-6) [5]. In humans, it has been shown that increasing dietary EPA and DHA was able to decrease 2-AG [6] or AEA [7]; however, other nutritional strategies to increase tissue n-3 LCPUFAs, as demonstrated with intake of cheese enriched in alpha-linolenic (ALA, 18:3n-3), conjugated linoleic (CLA, 18:2c9t11) and vaccenic (VA, 18:1t11) acids, were able to significantly decrease plasma levels of AEA in hypercholesterolemic patients [8]. On the other hand, no data are available on whether a diet deficient in n-3 and in n-6 fatty acids replaced by saturated fatty acids (SAFA) is able to modify EC and congeners tissue profile. It is well known that intake of an essential fatty acid deficient (EFAD) diet is characterized by growth retardation and weight loss [9], even though the mechanism of action is not quite well understood. ARA possesses essential functions, particularly in cellular signalling via its role of precursors for numerous derivatives such as prostaglandins, leukotrienes, hepoxilins and other eicosanoids including ECs which strongly influence body composition homeostasis [10]. Symptoms of n-6 fatty acid deficiency involves, initially, scaly skin, decreased growth and increased transepidermal water loss, all symptoms that seem to be attributable to an essential structural role of LA in O-acylated ceramides of the epidermal water permeability barrier [11]. A dietary intake of around 1 en% of LA should be enough to prevent these symptoms in animals and in humans [12]. An early symptom of n-3 fatty acids deficiency is delayed brain development due to their essential role for proper brain function, probably via their incorporation into specific cellular PL [13]. Humans in the Western world ingest far less n-3 fatty acids (around 1–3 g⁄d, mainly ALA and, to a lesser extent, EPA and DHA) than n-6 fatty acids (10–20 g/d, mainly LA). The dietary intake of EPA and DHA varies greatly between individuals and between geographical populations and is mainly related to the dietary intake of seafood. It is well evident that EPA and DHA can inhibit the in vitro production of ARA-derived eicosanoids [14], but the in vivo formation seems to be much less influenced by dietary intake of EPA and DHA [14].

Introduction

Methods

Results

Discussion

References

Abstract

Background: In some Dutch pancreatic surgery centers, patients who underwent pancreatoduodenectomy (PD) for ampullary cancer undergo surveillance for colorectal cancer (CRC), since an association is suggested in contemporary literature. This study aimed to examine the CRC incidence after PD for ampullary cancer in four pancreatic surgery centers and a Dutch nationwide cohort. Methods: All patients who underwent resection of ampullary cancer from 2005 through 2017 at four centers were included. All colonoscopies and CRC diagnoses in these patients were recorded. In addition all PDs for ampullary cancer in the Dutch Pathology Registry (2000-2017) were recorded along with the CRC diagnoses and compared with an age, sex, and year-matched cohort. Results: Out of 287 included patients by the four centers, 11% underwent a colonoscopy within one year after PD. Eight (2.7%) were diagnosed with CRC before PD and two (0.7%), at 14 and 72 months after PD. In the nationwide cohort comparison, the CRC incidence was similar before (2.6% versus 1.9%, P = 0.424) and after surgery (2.1% versus 3.1%, P = 0.237). Within one year after PD, the incidence was 0.3% compared to 0.6% in the matched controls (P = 0.726) Conclusions: The current study could not find an increased risk of CRC in patients with resected ampullary cancer. Therefore, there is insufficient justification to screen for CRC in patients with resected ampullary cancer.

Introduction

Ampullary cancer is a rare malignancy that accounts for approximately 0.2% of all gastrointestinal cancers.[1] Due to its origin distal to the bile and pancreatic duct confluence at the duodenal outflow, the onset of symptoms (e.g. biliary obstruction) is early compared to most other periampullary and pancreatic tumors. As a consequence, resection rates of ampullary cancers reach up to 92%[2] and the reported 5-year survival rates range from 38 to 67%.[3-5] Several reports have suggested an increased incidence of colorectal polyps and malignancies in patients with ampullary cancer. Ampullary cancer in some patients is associated with hereditary colorectal cancer (CRC) syndromes, such as hereditary non-polyposis colorectal cancer (HNPCC) [6] and familial adenomatous polyposis (FAP).[7-9] However, in ampullary cancer patients without these syndromes, the CRC incidence is also reported to be higher than in age-adjusted control groups.[10, 11] This association has led to colorectal surveillance in patients who underwent pancreatoduodenectomy (PD) for ampullary cancer in some pancreatic cancer centers in the Netherlands. The yield of routine colonoscopy within one year after surgery is subject of debate.

Colon cancer is one of the most commonly detected pathology and is the third worldwide cause of death in the US and Europe and ranks second with regard to the incidence of malignant tumors in population. Raman spectroscopy and imaging can be used for colon cancer detection and bioanalytical characterization of noncancerous and pathologically changed tissues. These studies included Raman spectroscopy measurement of not fixed and not stained tissues samples. Presented study included patients from Poland, who were ≥18 years of age and underwent colon cancer surgery. Outcomes were measured using confocal Raman microscope, spectroscopy results were compared with traditional histopathology analysis outcomes. DNA, lipids, proteins and carotenoids can be treated as biomarkers of cancerogenesis. Ratios: 751/1156 (DNA/Carotenoids), 1228/1332 (β -sheet/α -helix proteins conformation), 1586/1004 (Phosphorylated proteins/Proteins), 2854/2935 (Lipids/Proteins) can be used to differentiate noncancerous and cancerous human sigmoid colon mucosa based on Raman spectroscopy and imaging. We have proved that Raman spectroscopy and imaging are a powerful technique to distinguish between noncancerous and cancerous human sigmoid colon mucosa and to characterize biochemical composition of multilayer sigmoid colon tissues samples.

Introduction

Nowadays Raman spectroscopy and imaging have been recognized as a powerful tool in bioanalytical, biochemical and medical applications. High sensitivity and specificity, above 90%, especially related to the fingerprint region of Raman spectr a , offer precise identification of biomarkers based on their unique vibrations. The great advantage of Raman spectroscopy and imaging is also related to the fact that samples analysis doesn’t require any staining, which is beneficial in terms of time -consuming protocols and analysis costs . As a consequence , Raman based methods including Raman spectroscopy and imaging have emerged in last years as one of the most important alternative s for traditional ex vivo human tissue examination by H&E staining and highly efficient tool for biomedical applications [ 1 – 11]. A considerable progress in the field of in vivo – clinical assessment, especially due to the spectroscopic fiber technologies is also observed [12, 13]. Colon cancer , one of the most commonly detected pathology is the third worldwide cause of death with mortality around 60% in the United States and Europe and ranks second with regard to the incidence of malignant tumors in population [14]. The main endoscopic examination used in clinical practice for colon cancer screening is colonoscopy. However, colonoscopy has some disadvantages and risk such as colonic perforation occurring in approximately 1 in 1000 cases, or hemorrhagic complications that may occur during or after colonoscopy. When combined with anesthesia, other difficulties may include cardiovascular complications such as a temporary drop in blood pressure, the risk of blood clots, pulmonary embolism or deep vein thrombosis.

1- Introduction

2- Targeting the “undruggable” using gene silencing drugs

3- Nanoparticles as a delivery vehicle for siRNA

4- Current state of play of gene silencing nanodrugs in the clinic

5- Gene silencing nanomedicines for the treatment of pancreatic cancer

6- Challenges and opportunities in pancreatic cancer

7- Concluding remarks

References

Abstract

Pancreatic cancer is predicted to be the second leading cause of cancer-related death by 2025. The best chemotherapy only extends survival by an average of 18 weeks. The extensive fibrotic stroma surrounding the tumor curbs therapeutic options as chemotherapy drugs cannot freely penetrate the tumor. RNA interference (RNAi) has emerged as a promising approach to revolutionize cancer treatment. Small interfering RNA (siRNA) can be designed to inhibit the expression of any gene which is important given the high degree of genetic heterogeneity present in pancreatic tumors. Despite the potential of siRNA therapies, there are hurdles limiting their clinical application such as poor transport across biological barriers, limited cellular uptake, degradation, and rapid clearance. Nanotechnology can address these challenges. In fact, the past few decades have seen the conceptualization, design, pre-clinical testing and recent clinical approval of a RNAi nanodrug to treat disease. In this review, we comment on the current state of play of clinical trials evaluating siRNA nanodrugs and review pre-clinical studies investigating the efficacy of siRNA therapeutics in pancreatic cancer. We assess the physiological barriers unique to pancreatic cancer that need to be considered when designing and testing new nanomedicines for this disease.

Introduction

Pancreatic ductal adenocarcinoma [referred to as pancreatic cancer (PC)] is the fourth leading cause of cancer-related deaths in developed countries with a dismal five-year survival rate of 8% [1]. PC has seen little improvement in patient survival in the past four decades and is projected to be the second leading cause of cancer mortality by 2025 [2]. Unfortunately, PC is often diagnosed at an advanced stage with the development of metastatic spread at diagnosis [3]. Surgical resection improves patient survival, but only 15-20% of patients have surgically resectable tumors and long-term survival after surgery remains poor [3, 4]. Tragically, our best chemotherapy treatments only improve life by an average of 8-16 weeks [4] and there is an urgent need to develop more effective treatments.

Statement of Search Strategies Used and Sources of Information

Introduction

The Clinical Evidence for Brachytherapy as a Treatment for Dysphagia

Cost Comparison of Brachytherapy and Stent Insertion

Why is Brachytherapy so Infrequently Used and Should it be Used More?

Conclusions and Recommendations

References

Abstract

ysphagia in people with advanced oesophageal cancer can be treated by oesophageal stents, external beam radiotherapy (EBRT) and intraluminal brachytherapy. Despite guidelines recommending brachytherapy for patients with a predicted life expectancy exceeding 3 months, its uptake in the UK has been limited. Here we examine the strength of the evidence supporting the use of brachytherapy compared with oesophageal stents and EBRT and possible reasons for its limited uptake. Trials and observational studies suggest brachytherapy alone confers a benefit to patients, but its impact is less immediate than oesophageal stents; the evidence on effectiveness and value-for-money is limited. Moreover, stronger evidence will probably be insufficient to increase uptake, due to the extra complexity of delivery compared with stents and EBRT and a lack of experience among specialists.

Introduction

People with oesophageal cancer often have a poor prognosis because they are diagnosed with advanced disease or are too frail to undergo curative treatment. For these reasons, oesophageal cancer is the seventh most common cause of death due to cancer in the UK despite being the 13th most common type of tumour [1]. Most patients are unsuitable for curative treatment and the aim of their treatment is primarily either to extend life expectancy or reduce the impact of symptoms on quality of life, although the latter is perhaps the dominant consideration. Among patients with stage IV cancer, recent population-based figures show life expectancy remains poor, with 1-year relative survival rates of 25.3 and 21.3% for squamous cell and adenocarcinoma tumours, respectively [2]. Dysphagia is a common, debilitating symptom among patients with advanced oesophageal cancer and can present with various stages of severity, such as restricting patients to eating specific solids, to swallowing only liquids or preventing anything from being ingested orally. Various therapies are available to alleviate dysphagia, including oesophageal stent insertion, external beam radiotherapy (EBRT), brachytherapy, laser therapy, photodynamic therapy and argon plasma coagulation [3].

Introduction

Advances in imaging

Advances in endoscope design

Advances in therapeutic endoscopy

Key references

Abstract

The requirement for efficient endoscopic visualization and instrumentation has increased over the past decade given the considerable burden that luminal disorders of the gastrointestinal tract exert on individuals and healthcare economies. The push for greater diagnostic yield has driven advances in optical physics and bioengineering, which are revolutionizing diagnostic and therapeutic endoscopy. This article highlights emerging technologies since our last review, focusing on advances in imaging and endoscope design, and how these are shaping the therapeutic approach to diseases of the human gastrointestinal tract. Their application to improving diagnostic ability and patient care, as well as their limitations, are discussed.

Introduction

High-definition (HD) digital technology has moved endoscopic imaging to a new dimension. Endoscopic innovations have arisen from the explosion of technical achievements through the interaction between physicians and engineers, and the incorporation of technology from other fields such as computing, artificial intelligence and physics. These endoscopic advances are important to meet the need that we are still missing upper gastrointestinal (GI) cancers and colonic polyps. A meta-analysis showed that 11.3% of upper GI cancers were missed during endoscopy up to 3 years before diagnosis.1 Hand in hand with these advancements in imaging, there is a continuing evolution of the ergonometric design of endoscopes, with dedicated accessories that allow increasing applications of therapeutic endoscopy. The endoscopic treatment of early cancers of the GI tract continues to advance at a pace and is being constantly driven by improved imaging.

2- Methods

3- Results

4- Discussion

5- Conclusions

References

Introduction

Acute pancreatitis (AP) is an infammatory disease of the pancreas, with 10–20% of patients progressing to multiple organ failure coupled with a high mortality rate. Te incidence of AP is increasing year by year, consistent with an increase in the number of people with metabolic syndrome. Te incidence of local and systemic complications, especially mortality in patients with AP with metabolic syndrome, is noteworthy [1]. Metabolic syndrome is a clinical diagnosis based on the identifcation of related metabolic status. It can increase the risk of cardiovascular diseases, including diabetes, dyslipidemia, arterial hypertension, and abdominal obesity [2]. Abdominal obesity, a typical phenotype of metabolic syndrome, has been demonstrated to be an independent risk factor for AP [3]. Many clinical studies have confrmed that abdominal obesity can increase the severity of AP, prolong hospital stay, and increase the intensive care unit occupancy rate and mortality [4, 5]. Nonalcoholic fatty liver disease (NAFLD) is a phenotype of metabolic syndrome in the liver. NAFLD is related to all the components of metabolic syndrome and may be considered an additional component of the disease itself [6].

Conclusions

In summary, our results demonstrated that the presence of NAFLD at admission portends a higher risk of moderately severe and SAP, as well as a higher risk of SIRS and organ failure. In the clinical environment, we should pay close attention to the phenomenon of NAFLD aggravation of the severity of AP.