Treatment Of Chronic Pancreatitis Research Articles

High-mobility group box 1 fragment ameliorates chronic pancreatitis induced by caerulein in mice.

Chronic pancreatitis (CP) is a progressive disease characterized by pancreatic fibrosis for which effective treatment options are lacking. Mesenchymal stem cells (MSCs) have shown potential for fibrosis treatment but face limitations in clinical application. The high-mobility group box 1 (HMGB1) fragment mobilizes MSCs from bone marrow into the blood and has emerged as a promising therapeutic agent for tissue regeneration in various pathological conditions. The aim of this study was to investigate the potential therapeutic effects of systemic administration of the HMGB1 fragment in a mouse model of CP. A caerulein-induced CP mouse model was used, and the HMGB1 fragment was administered by tail vein injection. Parameters such as body weight, pancreatic tissue damage, fibrosis, inflammatory cytokine expression, and collagen-related gene expression were evaluated using various assays, including immunohistochemistry, real-time PCR, serum analysis, and single-cell transcriptome analysis. And the migration of MSCs to the pancreas was evaluated using the parabiosis model. Administration of the HMGB1 fragment was associated with significant improvements in pancreatic tissue damage and fibrosis. It suppressed the expression of inflammatory cytokines and activated platelet-derived growth factor receptor-α+ MSCs, leading to their accumulation in the pancreas. The HMGB1 fragment also shifted gene expression patterns associated with pancreatic fibrosis toward those of the normal pancreas. Systemic administration of the HMGB1 fragment demonstrated therapeutic efficacy in attenuating pancreatic tissue damage and fibrosis in a CP mouse model. These findings highlight the potential of the HMGB1 fragment as a therapeutic target for the treatment of CP.

Transcriptomic analysis reveals the crosstalk between type 2 diabetes and chronic pancreatitis.

Mounting evidence highlights a strong association between chronic pancreatitis (CP) and type 2 diabetes (T2D), although the exact mechanism of interaction remains unclear. This study aimed to investigate the crosstalk genes and pathogenesis between CP and T2D. Transcriptomic gene expression profiles of CP and T2D were extracted from Gene Expression Omnibus, respectively, and the common differentially expressed genes (DEGs) were subsequently identified. Further analysis, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction, transcription factors (TFs), microRNA (miRNAs), and candidate chemicals identification, was performed to explore the possible common signatures between the two diseases. In total, we acquired 281 common DEGs by interacting CP and T2D datasets, and identified 10 hub genes using CytoHubba. GO and KEGG analyses revealed that endoplasmic reticulum stress and mitochondrial dysfunction were closely related to these common DEGs. Among the shared genes, EEF2, DLD, RAB5A, and SLC30A9 showed promising diagnostic value for both diseases based on receiver operating characteristic curve and precision-recall curves. Additionally, we identified 16 key TFs and 16 miRNAs that were strongly correlated with the hub genes, which may serve as new molecular targets for CP and T2D. Finally, candidate chemicals that might become potential drugs for treating CP and T2D were screened out. This study provides evidence that there are shared genes and pathological signatures between CP and T2D. The genes EEF2, DLD, RAB5A, and SLC30A9 have been identified as having the highest diagnostic efficiency and could be served as biomarkers for these diseases, providing new insights into precise diagnosis and treatment for CP and T2D.

Evaluating the Efficacy of Antioxidant Therapy in Enhancing the Quality of Life of Chronic Pancreatitis Patients: A Systematic Review.

Chronic pancreatitis (CP), an inflammatory disease characterized by irreversible pancreatic changes and progressive fibrosis, significantly impairs patients' quality of life. This systematic review aims to assess the efficacy of antioxidant therapy in enhancing the quality of life of CP patients. Focusing on the role of oxidative stress in CP pathogenesis, we explored several databases for studies evaluating the impact of antioxidant supplementation. The review included randomized controlled trials and cohort studies reporting pain frequency, intensity, and overall quality of life measures. Findings from these studies present a mixed view of the efficacy of antioxidants in CP, with some suggesting benefits in symptom management, while others show inconsistency in improving patient outcomes. The review concludes that while antioxidant therapy holds potential, especially in symptom alleviation, there is a need for more rigorous, larger-scale studies to confirm its effectiveness in CP management and to establish standardized treatment protocols. The incorporation of antioxidants into CP treatment plans should be approached with personalized care, considering the varied responses observed in different patient populations.

Pancreas-directed AAV8-hSPINK1 gene therapy safely and effectively protects against pancreatitis in mice

ObjectiveCurrently, there is no cure for chronic pancreatitis (CP). Germline loss-of-function variants in SPINK1 (encoding trypsin inhibitor) are common in patients with CP and are associated with acute attacks and...

COMP promotes pancreatic fibrosis by activating pancreatic stellate cells through CD36-ERK/AKT signaling pathways

BackgroundPancreatic fibrosis is one of the most important pathological features of chronic pancreatitis (CP) and pancreatic stellate cells (PSCs) are the key cells of fibrosis. As an extracellular matrix (ECM) glycoprotein, cartilage oligomeric matrix protein (COMP) is critical for collagen assembly and ECM stability and recent studies showed that COMP exert promoting fibrosis effect in the skin, lungs and liver. However, the role of COMP in activation of PSCs and pancreatic fibrosis remain unclear. We aimed to investigate the role and specific mechanisms of COMP in regulating the profibrotic phenotype of PSCs and pancreatic fibrosis. MethodsELISA method was used to determine serum COMP in patients with CP. Mice model of CP was established by repeated intraperitoneal injection of cerulein and pancreatic fibrosis was evaluated by Hematoxylin-Eosin staining (H&E) and Sirius red staining. Immunohistochemical staining was used to detect the expression changes of COMP and fibrosis marker such as α-SMA and Fibronectin in pancreatic tissue of mice. Cell Counting Kit-8, Wound Healing and Transwell assessed the proliferation and migration of human pancreatic stellate cells (HPSCs). Western blotting, qRT-PCR and immunofluorescence staining were performed to detect the expression of fibrosis marker, AKT and MAPK family proteins in HPSCs. RNA-seq omics analysis as well as small interfering RNA of COMP, recombinant human COMP (rCOMP), MEK inhibitors and PI3K inhibitors were used to study the effect and mechanism of COMP on activation of HPSCs. ResultsELISA showed that the expression of COMP significantly increased in the serum of CP patients. H&E and Sirius red staining analysis showed that there was a large amount of collagen deposition in the mice in the CP model group and high expression of COMP, α-SMA, Fibronectin and Vimentin were observed in fibrotic tissues. TGF-β1 stimulates the activation of HPSCs and increases the expression of COMP. Knockdown of COMP inhibited proliferation and migration of HPSCs. Further, RNA-seq omics analysis and validation experiments in vitro showed that rCOMP could significantly promote the proliferation and activation of HPSCs, which may be due to promoting the phosphorylation of ERK and AKT through membrane protein receptor CD36. rCOMP simultaneously increased the expression of α-SMA, Fibronectin and Collagen I in HPSCs. ConclusionIn conclusion, this study showed that COMP was up-regulated in CP fibrotic tissues and COMP induced the activation, proliferation and migration of PSCs through the CD36-ERK/AKT signaling pathway. COMP may be a potential therapeutic candidate for the treatment of CP. Interfering with the expression of COMP or the communication between COMP and CD36 on PSCs may be the next direction for therapeutic research.

Safety, Tolerability, and Dose-Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis: Protocol for a Phase 1 Clinical Trial to Determine Safety and Identify Side Effects.

Chronic abdominal pain is the hallmark symptom of chronic pancreatitis (CP), with 50% to 80% of patients seeking medical attention for pain control. Although several management options are available, outcomes are often disappointing, and opioids remain a mainstay of therapy. Opioid-induced hyperalgesia is a phenomenon resulting in dose escalation, which may occur partly because of the effects of opioids on voltage-gated sodium channels associated with pain. Preclinical observations demonstrate that the combination of an opioid and the antiseizure drug lacosamide diminishes opioid-induced hyperalgesia and improves pain control. In this phase 1 trial, we aim to determine the safety, tolerability, and dose-limiting toxicity of adding lacosamide to opioids for the treatment of painful CP and assess the feasibility of performance of a pilot study of adding lacosamide to opioid therapy in patients with CP. As an exploratory aim, we will assess the efficacy of adding lacosamide to opioid therapy in patients with painful CP. Using the Bayesian optimal interval design, we will conduct a dose-escalation trial of adding lacosamide to opioid therapy in patients with painful CP enrolled in cohorts of size 3. The initial dose will be 50 mg taken orally twice a day, followed by incremental increases to a maximum dose of 400 mg/day, with lacosamide administered for 7 days at each dose level. Adverse events will be documented according to Common Terminology Criteria for Adverse Events (version 5.0). As of December 2023, we have currently enrolled 6 participants. The minimum number of participants to be enrolled is 12 with a maximum of 24. We expect to publish the results by March 2025. This trial will test the feasibility of the study design and provide reassurance regarding the tolerability and safety of opioids in treating painful CP. It is anticipated that lacosamide will prove to be safe and well tolerated, supporting a subsequent phase 2 trial assessing the efficacy of lacosamide+opioid therapy in patients with painful CP, and that lacosamide combined with opiates will lower the opioid dose necessary for pain relief and improve the safety profile of opioid use in treating painful CP. Clinicaltrials.gov NCT05603702; https://clinicaltrials.gov/study/NCT05603702. PRR1-10.2196/50513.

Pancreatic quantitative sensory testing to predict treatment response of endoscopic therapy or surgery for painful chronic pancreatitis with pancreatic duct obstruction: study protocol for an observational clinical trial

IntroductionTreatment for abdominal pain in patients with chronic pancreatitis (CP) remains challenging in the setting of central nervous system sensitisation, a phenomenon of remodelling and neuronal hyperexcitability resulting from persistent...

Treatment of chronic pancreatitis in a super-aging society

Treatment of chronic pancreatitis in a super-aging society

Surgical Interventions in Chronic Pancreatitis: A Systematic Review of Their Impact on Quality of Life.

This systematic review evaluates the efficacy of surgical interventions in improving the quality of life for patients with chronic pancreatitis (CP). A thorough literature search, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, identified 11 studies that focused on patient-reported outcomes after surgical treatments, including pancreatic resections, drainage procedures, and duodenum-preserving head resections. The findings indicate that organ-preserving procedures, notably the Frey and Beger operations, significantly enhance pain control and overall quality of life while reducing analgesic dependency. This review provides crucial insights into the long-term efficacy and comparative benefits of different surgical approaches, highlighting the need for personalized surgical strategies in CP management. It emphasizes the necessity for standardized outcome measures and further comparative research to refine CP treatment protocols.

Citric Acid Loaded Hydrogel-Coated Stent for Dissolving Pancreatic Duct Calculi.

In recent years, the incidence of chronic pancreatitis has increased significantly. Pancreatic calculi obstruct the pancreatic duct and induce abdominal pain in the patients. Pancreatic duct stenting is the major treatment option for chronic pancreatitis with calculi. In this study, a new kind of drug-eluting stent, a pancreatic stent coated by methacrylated gelatin (GelMA) hydrogel loaded with citric acid (CA), was designed for the interventional treatment of pancreatic duct calculi. The CA loading capacity reached up to 0.7 g CA/g hydrogel-coated stent. The GelMA hydrogel coating has higher mechanical strength and lower swelling performance after loading with CA. The in vitro experiments of stents exhibited good performance in CA sustained release and the calculi can be dissolved in almost 3 days. The stents also showed good blood compatibility and cell compatibility. This research has important clinical value in the treatment of chronic pancreatitis with pancreatic calculi.

Predictive Factors Correlated with Successful Early Endoscopic Removal of Pancreaticolithiasis in Chronic Pancreatitis after Extracorporeal Shock Wave Lithotripsy.

The treatment of chronic pancreatitis (CP) and symptomatic pancreatic duct (PD) calculi often involves techniques like endoscopic retrograde cholangiopancreatography (ERCP), extracorporeal shock wave lithotripsy (ESWL), or a combination of both. However, identifying predictive factors for the successful removal of these calculi remains variable. This study aimed to determine the factors predicting successful ESWL and endoscopic removal in CP and PD calculi patients. We examined data from CP patients who underwent complete PD calculi removal via ESWL combined with ERCP between July 2012 and 2022, and assessed baseline characteristics, imaging findings, and treatment details. Patients were categorized into early- and late-endoscopic complete removal groups (EER and LER groups, respectively). Of the 27 patients analyzed, 74.1% were male with an average age of 44 ± 9.6 years. EER was achieved in 74% of the patients. Patients in the EER group exhibited smaller PD calculi diameter (8.5 vs. 19 mm, p = 0.012) and lower calculus density (964.6 vs. 1313.3 HU, p = 0.041) compared to the LER group. Notably, PD stricture and the rate of PD stent insertion were not different between the groups. A calculus density threshold of 1300 HU on non-contrast CT demonstrated 71% sensitivity and 80% specificity in predicting EER. Smaller and low-density PD calculi may serve as predictors for successful EER, potentially aiding in the management of CP patients with PD calculi.

Management of chronic pancreatitis: recent advances and future prospects.

As a progressive fibroinflammatory disease, chronic pancreatitis (CP) often manifests as recurrent bouts of abdominal pain with or without complications, causing a heavy burden of health care. In recent years, some meaningful insights into the management of CP have been obtained from randomized controlled trials, systematic reviews, and meta-analyses, which were of great importance. Based on this research, it is shown that there are various treatments for CP. Therefore, it is of great importance to choose a suitable strategy for patients with CP individually. Relevant evidence on the management of CP was summarized in this review, including nutrition supplements, medication, endoscopy, surgery, exploration of novel therapies as well as evaluation and prediction of treatment response.

EVALUATING LACTOFERRIN AND CALPROTECTIN AS MARKERS OF INTESTINAL INFLAMMATION INCHRONIC PANCREATITIS.

The treatment of chronic pancreatitis does not consistently solve intestinal abnormalities, and despite the implementation of various therapeutic measures, patients often continue to experience persistent diarrhea. Therefore, it is imperative to recognize that diarrhea may stem from factors beyond pancreatic insufficiency, and intestinal inflammation emerges as a potential contributing factor. The aim of this study was to assess fecal lactoferrin and calprotectin levels as indicators of intestinal inflammation in patients with chronic pancreatitis experiencing persistent diarrhea. In this study, 23 male patients with chronic pancreatitis primarily attributed to alcohol consumption and presenting with diarrhea (classified as Bristol stool scale type 6 or 7), underwent a comprehensive evaluation of their clinical and nutritional status. Fecal lactoferrin and calprotectin levels were mea-sured utilizing immunoassay techniques. The average age of the participants was 54.8 years, 43.5% had diabetes, and 73.9% were smokers. Despite receiving enzyme replacement therapy and refraining from alcohol for over 4 years, all participants exhibited persistent diarrhea, accompanied by elevated calprotectin and lactoferrin levels indicative of ongoing intestinal inflammation. The findings of this study underscore that intestinal inflammation, as evidenced by elevated fecal biomarkers calprotectin and lactoferrin, may contribute to explaining the persistence of diarrhea in patients with chronic pancreatitis. • Exploration of intestinal inflammation in chronic pancreatitis patients with altered bowel habits. • Assessment of 23 patients using lactoferrin and calprotectin as intestinal inflammation biomarkers. • Intestinal inflammation was detected in all patients; positive correlation between both biomarkers. • Established connection between altered bowel habits and intestinal inflammation in chronic pancreatitis.

Nationwide Outcome of Tailored Surgery for Symptomatic Chronic Pancreatitis based on Pancreatic Morphology

Objective: To determine the nationwide use and outcome of tailored surgical treatment for symptomatic chronic pancreatitis (CP) as advised by recent guidelines. Summary background data: Randomized trials have shown that surgery is superior to endoscopy in patients with symptomatic CP, although endoscopy remains popular Recent guidelines advice to “tailor surgery” based on pancreatic morphology meaning that the least extensive procedure should be selected based on pancreatic morphology. However, nationwide, and multicenter studies On tailored surgery for symptomatic CP are lacking. Methods: Nationwide multicenter retrospective analysis of consecutive patients undergoing surgical treatment for symptomatic CP in all seven Dutch university medical centers (2010-2020). Outcomes included volume trend, major complications, 90-day mortality, postoperative opioid use and clinically relevant pain relief. Surgical treatment was tailored based on the size of the main pancreatic duct and pancreatic head (e.g. surgical drainage for a dilated pancreatic duct, and normal size pancreatic head). Results: Overall, 381 patients underwent surgery for CP: 127 surgical drainage procedures ( 33%; mostly extended lateral pancreaticojejunostomy), 129 duodenum-preserving pancreatic head resections (DPPHR, 34%, mostly Frey), and 125 formal pancreatic resections (33%, mostly distal pancreatectomy). The annual surgical volume increased slightly (Pearson r=0.744). Mortality (90-day) occurred in 6 patients (2%), and was non-significantly lower after surgical drainage (0%, 3%, 2%; P=0.139). Major complications (12%, 24%, 26%; P=0.012), postoperative pancreatic fistula grade B/C (0%, 3%, 22%; P=0.038), surgical reintervention (4%, 16%, 12%; P=0.006), and endocrine insufficiency ( 14%, 21%, 43%; P<0.001) occurred less often after surgical drainage. After a median follow-up of 11 months [IQR 3-23] good rates of clinically relevant pain relief ( 83%, 69%, 80%; P=0.082) were observed and 81% of opioid users had stopped using (83%, 78%, 84%, P=0.496). Conclusion: The use of surgery for symptomatic CP increased over the study period. Drainage procedures were associated with the best safety profile and excellent functional outcome, highlighting the importance of tailoring surgery based on pancreatic morphology.

Daily Pain Experiences in Chronic Pancreatitis: Identifying Pain Phenotypes.

Pain, the hallmark symptom of chronic pancreatitis (CP), remains difficult to assess. To capture the variability of pain that patients can experience day to day, this study used pain diaries to describe daily pain experiences and identify pain phenotypes. This study is a secondary data analysis from a pilot trial examining cognitive behavioral therapy for pain treatment in CP. Before treatment, patients completed an online daily pain diary using the Brief Pain Inventory for 7 days. Using indicators of pain magnitude, pain variability, pain synchrony along with least, worst, and average pain intensity levels, we identified pain patterns using K-means clustering. Of 30 patients in the pilot trial, a total of 27 patients (mean age of 49.8 years, 80% women) had complete data to include in this report. Four clusters were identified: cluster 1, lowest pain magnitude (n = 3); cluster 2, moderate pain magnitude and high pain variability (n = 4); cluster 3, moderate pain magnitude and low pain variability (n = 9); and cluster 4, highest pain magnitude and lowest pain variability (n = 11). Daily pain diaries offer a novel way of evaluating the dynamic pain experiences in CP. Although 4 distinct pain patterns were identified, further studies are needed to validate these findings.

Assessment of the efficacy of the combination of α-lipoic acid preparation and synbiotics in the protocol therapy of hypothyroidism combined with chronic pancreatitis

Hypothyroidism (Ht) is a common clinical condition with variable prevalence. This disease is often associated with chronic pancreatitis (CP). Consensus exists regarding the necessity to treat patients with Ht in comorbidity with CP to reduce the risk of complications and the frequency of exacerbations, to reduce the activity of the progression of the pathological process, and to improve the quality of life.
 Objective — to evaluate the effects of additional use of thioctic acid and synbiotics combination in the conventional treatment on the indicators of the functional state of thyroid gland (THG) and pancreas in patients with Ht in comorbidity with CP.
 Materials and methods. Investigation involved 107 patients with a comorbid course of Ht and CP, who were divided into 3 groups according to the complex treatment programs: the first group consisted of 32 subjects, who received protocol treatment (PT) of Ht and CP, the second included 36 patients (PT + α‑lipoic acid preparation (Dialipon Turbo), the third — 39 patients (PT + α‑lipoic acid preparation + synbiotic (Lactimak Forte). The groups were comparable by age and gender. The functional state of the pancreas was assessed using the level of fecal α‑elastase (enzyme immunoassay), pancreatic α‑amylase (immunochemical method), and the coprogram index in points. Thyroid function was assessed by the levels of thyrotropic hormone TSH, free triiodothyronine T3 and free thyroxine T4 (chemiluminescent immunoassay). The obtained data were processed with statistical methods.
 Results. The positive dynamics was established in all groups, but the degree of its expression differed. Thus, the level of fecal α‑elastase increased by 57.54% — in the 1st group, by 78.27% — in the 2nd group, by 89.94% — in the 3rd group; pancreatic α‑amylase decreased by 29.68% — in the 1st group, by 39.19% — in the 2nd group, by 42.44% — in the 3rd group; the total coprogram index decreased by 25.11% — in the 1st group, by 47.57% — in the 2nd group, by 84.91% — in the 3rd group. T3 dynamics was 13.9% in the 1st group, 48.69% in the 2nd group, 78.17% in the 3rd group. Dynamics of T4 — 11.3% in the 1st group, 29.98% — in the 2nd group, 35.37% — in the 3rd group. The dynamics of TSH was 19.66%, 31.81%, 69.41%, respectively.
 Conclusions. It has been proven that the use of the proposed treatment regimen including the combination of the drug α‑lipoic acid and the synbiotic Laktimak Forte promoted the improvement of pancreas functions and levels of thyroid hormones compared to those in the group of protocol treatment: the level of fecal α‑elastase increased by 89.94%; pancreatic α‑amylase — by 42.44%; coprogram index — by 84.91%; T3 — by 78.17%; T4 — by 35.37%; TSH — by 69.41% (p <0.01).

A Review of Recent Chinese Clinical Studies on Herbal Medicine Treatments for Chronic Pancreatitis

Objectives: This study summarizes current trends and results in clinical studies on herbal medicine treatments for chronic pancreatitis.Methods: Studies published from 2014 to 2023 were searched for on the China National Knowledge Infrastructure (CNKI), PubMed, and KMbase using the keywords “chronic pancreatitis”, “herbal medicine”, “herb”, “만성 췌장염”, and “한약”. The studies were analyzed according to year, study design, characteristics of the patients, and traditional Chinese medicine (TCM) intervention.Results: In total, 23 studies were selected. There were 21 randomized controlled trials and 2 case-control studies. The most common herbal prescriptions were Qingyi-tang (淸胰湯), <i>Radix Bupleuri</i> (柴胡), <i>Radix Paeoniae Alba</i> (白芍藥), <i>Radix Glycyrrhizae</i> (甘草), <i>Radix Scutellariae</i> (黃芩), and <i>Rhei Rhizoma</i> (大黃). In all the studies, herbal medicine treatments were effective in the treatment of chronic pancreatitis, and efficacy was assessed using clinical symptoms, physicochemical examination, radiological examination, and relapse.Conclusions: Herbal medicine treatment can be an effective treatment for chronic pancreatitis and has potential in clinical practice.

Reg family proteins contribute to inflammation and pancreatic stellate cells activation in chronic pancreatitis

Chronic pancreatitis (CP) is a disease characterized by the inflammation and destruction of pancreatic tissue, leading to the replacement of functional tissue with fibrotic tissue. The regenerating gene (Reg) family proteins have recently been implicated in the repair and regeneration of inflamed pancreatic tissue, though the exact mechanisms of their involvement in the pathogenesis of CP are not yet fully understood. To investigate the role of Reg family proteins in CP, we generated global knockout mice (Reg−/−) for Reg1-3 (Reg1,2,3a,3b,3d,3g) genes using the CRISPR/Cas9 system. We then investigated the effect of Reg family protein deficiency in a genetic model of CP (X-SPINK1) mice by knocking out Reg1-3 genes. We examined pancreatic morphology, inflammatory cytokines expression, and activation of pancreatic stellate cells (PSCs) at different ages. Reg−/− mice showed no abnormalities in general growth and pancreas development. Deficiency of Reg1-3 in CP mice led to a reduction in pancreatic parenchymal loss, decreased deposition of collagen, and reduced expression of proinflammatory cytokines. Additionally, Reg proteins were found to stimulate PSCs activation. Overall, our study suggests that Reg1-3 deficiency can lead to the remission of CP and Reg family proteins could be a potential therapeutic target for the treatment of CP.

Pancreatic Stellate Cells and the Targeted Therapeutic Strategies in Chronic Pancreatitis.

Chronic pancreatitis (CP) is a disease characterized by inflammatory recurrence that accompanies the development of pancreatic fibrosis. As the mystery of CP pathogenesis is gradually revealed, accumulating evidence suggests that the activation of pancreatic stellate cells (PSCs) and the appearance of a myofibroblast-like phenotype are the key gatekeepers in the development of CP. Targeting PSCs to prevent their activation and conversion to a myofibroblast-like phenotype, as well as increasing antioxidant capacity to counteract ongoing oxidative stress, are effective strategies for preventing or treating CP. Therefore, we reviewed the crosstalk between CP and pancreatic fibrosis, summarized the activation mechanisms of PSCs, and investigated potential CP therapeutic strategies targeting PSCs, including, but not limited to, anti-fibrosis therapy, antioxidant therapy, and gene therapy. Meanwhile, the above therapeutic strategies are selected in order to update the available phytopharmaceuticals as novel complementary or alternative approaches for the prevention and treatment of CP to clarify their potential mechanisms of action and their relevant molecular targets, aiming to provide the most comprehensive therapeutic treatment direction for CP and to bring new hope to CP patients.

Gut microbiota and pancreatic diseases: a microbiome-associated approach in the treatment of chronic pancreatitis

Intestinal microbiota is a factor that determines human health, maintains body homeostasis, and influences the development of pancreatic diseases (acute pancreatitis, chronic pancreatitis (CP), and cancer). Butyrate, acetate, propionate, and key short-chain fatty acids, which are synthesized by probiotic bacteria, have a significant effect on the functional pancreatic activity: anti-inflammatory effect, modulation of pancreatic β-cell function, regulation of pancreatic cell mass, and strengthening of the intestinal barrier function.
 It has been proven that the course of CP is associated with intestinal dysbiosis, bacterial overgrowth syndrome, a decrease in the levels of Firmicutes and Actinobacteria, and an increase in the levels of Proteobacteria phylum, Eubacterium rectale, Coprococcus, Sutterella, and Eubacterium ruminantium. Their predominance is related to exocrine pancreatic insufficiency, while Pseudomonas, Fusobacterium, and Ruminococcus gnavus are more common in CP patients without exocrine pancreatic insufficiency. Activation of pancreatic fibrogenesis is associated with an increase in Streptomyces, Turicibacter, Methylobacterium, Enterococcus, and Candidatus Paenicardiniummore.
 The mechanism of action of probiotics in pancreatic diseases is associated with improved functioning of the intestinal barrier, decreased BOS and the inflammatory process, and inhibition of the signaling pathway of oncogenesis. The microbiome-associated approach to treating CP is based on the additional administration of probiotics. The multicomponent probiotic Laktiale Multi can be the drug of choice.