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Lymphatic Function and Dysfunction: From Physiopathology to Therapy

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (15 July 2023) | Viewed by 10225

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Special Issue Editor

Prof. Dr. Mei Rosemary Fu

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Guest Editor

School of Nursing, Rutgers University, The State University of New Jersey, Camden, NJ 08102, USA
Interests: lymphatic function; lymphedema; tissue fluid homeostasis; fluid accumulation; fluid overload; limb volume; bioimpedance; fluid level; lymphatic pain; fatigue; symptoms; cancer; obesity; cardiovascular diseases; diabetes; chronic illness; lymphedema therapy; lymphatic and meditative exercises; integrative and complementary therapy; behavioral science; machine learning; microbiome; mycobiome; biomarkers; genomics; self-management; self-care; symptoms related to fluid accumulation

Special Issue Information

Dear Colleagues,

The lymphatic system is part of the circulatory and immune system. As a part of the immune system, the lymphatic system maintains immune surveillance. Lymphatic dysfunction may lead to abnormal physiological functions and pathological immune conditions. As a part of circulatory system, the lymphatic system is essential in regulating tissue fluid homeostasis and intestinal lipid absorption. Lymphatic dysfunction leads to primary lymphedema due to congenital lymphatic abnormality or secondary lymphedema due to cancer treatment, obesity, wounds, injury, or trauma. Basic and clinical research activity is growing on the role of the lymphatic system in regulating tissue fluid homeostasis and mitigating lymphedema, cardiovascular diseases (e.g., heart failure, hypertension, stroke), obesity, diabetes, metabolic syndrome, Alzheimer’s disease, wound healing, cancer, and tumor metastasis. Understanding lymphatic function and dysfunction is essential in finding a cure for lymphedema and chronic illnesses that can be mitigated by the lymphatic system.

The Special Issue "Lymphatic Function and Dysfunction: From Physiopathology to Therapy" aims to be a platform for researchers to showcase their cutting-edge research, systematic reviews and meta-analyses on the following topics (not an exhaustive list):

Basic research on physiology of normal lymphatic function and dysfunction;
Primary lymphedema;
Secondary lymphedema due to cancer, cancer treatment, obesity, wounds, injury, and trauma;
Lymphatic function and immune;
Fluid homeostasis, fluid overload, and symptoms related to fluid accumulation in cardiovascular diseases (heart failure, hypertension, stroke, etc.);
Lymphatic function and wound healing;
Lymphatic function and Alzheimer’s disease;
Lymphatic function and metabolic syndrome;
Lymphatic function and cancer and tumor metastasis;
Lymphatic pain, chronic pain, and myofascial pain;
Therapeutic exercises targeting lymphatic function for lymphedema, fluid overload, lymphatic pain, chronic pain, and symptoms related to fluid accumulation;
Complementary and integrative therapy for lymphatic dysfunction (e.g., lymphedema, fluid overload, lymphatic pain), chronic pain, and symptoms related to fluid accumulation.

Prof. Dr. Mei Rosemary Fu
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

lymphatic function
primary and secondary lymphedema
fluid accumulation
fluid overload
limb volume
bioimpedance
fluid level
lymphatic pain
chronic pain
myofascial pain
obesity
heart failure
hypertension
diabetes
lymphedema therapy
exercises
lymphatic exercises
integrative and complementary therapy
behavioral interventions
microbiome
mycobiome
biomarkers
genomics
molecular mechanism

Published Papers (4 papers)

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Research

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17 pages, 1269 KiB

Open AccessArticle

Significant Decrease in Glycated Hemoglobin, 2h-Post-Load Glucose and High-Sensitivity C-Reactive Protein Levels in Patients with Abnormal Body Mass Index after Therapy with Manual Lymphatic Drainage

by Klaudia Antoniak, Katarzyna Zorena, Marta Jaskulak, Rita Hansdorfer-Korzon, Małgorzata Mrugacz and Marek Koziński

Biomedicines 2022, 10(7), 1730; https://doi.org/10.3390/biomedicines10071730 - 18 Jul 2022

Cited by 2 | Viewed by 2101

Abstract

The objective of this study was to investigate the effect of manual lymphatic drainage (MLD) on the insulin resistance parameter (HOMA-IR), glycated hemoglobin (HbA1c), C-peptide, insulin, fasting plasma glucose (FPG), 2h-post-loadglucose (2h-PG) and the concentration of high-sensitivity C-reactive protein (hsCRP) in patients with abnormal body mass index. The study involved 30 patients, including patients with normal body weight (as a control group; group I; n = 14), overweight patients (group II; n = 9) and obese patients (group III; n = 7). Each patient underwent 10 sessions of MLD therapy, 3 times a week for 30 min. In addition, we measured body mass index (BMI) and waist-to-hip ratio (WHR) and performed body composition analysis as well as biochemical tests before MLD therapy (stage 0′) and after MLD therapy (stage 1′). A statistically significant correlation was demonstrated between the concentration of C-peptide, BMI, the amount of visceral adipose tissue (r = 0.87, p = 0.003; r = 0.76, p = 0.003, respectively), and the HOMA-IR index, BMI and the amount of visceral adipose tissue (r = 0.86, p = 0.005; r = 0.84, p = 0.042, respectively), before and after MLD therapy. In overweight patients (group II), a statistically significant (p = 0.041) decrease in the hsCRP level by 2.9 mg/L and a significant (p = 0.050) decrease in the 2h-PG level by 12 mg/dL after the MLD therapy was detected. Moreover, in the group of obese patients (group III), a statistically significant (p = 0.013) decrease in HbA1c level by 0.2% after MLD therapy was demonstrated. Our results indicate that MLD may have a positive effect on selected biochemical parameters, with the most favorable changes in overweight patients. Further studies in a larger number of patients are warranted to confirm our findings, to test in-depth their mechanism, and to investigate clinical benefits of this alternative therapy in patients with abnormal body mass index. Full article

(This article belongs to the Special Issue Lymphatic Function and Dysfunction: From Physiopathology to Therapy)

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24 pages, 5426 KiB

Open AccessArticle

Paneth Cells Regulate Lymphangiogenesis under Control of Microbial Signals during Experimental Portal Hypertension

by Mohsin Hassan, Oriol Juanola, Irene Keller, Paolo Nanni, Witold Wolski, Sebastián Martínez-López, Esther Caparrós, Rubén Francés and Sheida Moghadamrad

Biomedicines 2022, 10(7), 1503; https://doi.org/10.3390/biomedicines10071503 - 25 Jun 2022

Cited by 4 | Viewed by 2361

Abstract

Intestinal microbiota can modulate portal hypertension through the regulation of the intestinal vasculature. We have recently demonstrated that bacterial antigens activate Paneth cells (PCs) to secrete products that regulate angiogenesis and portal hypertension. In the present work we hypothesized that Paneth cells regulate the development of lymphatic vessels under the control of intestinal microbiota during experimental portal hypertension. We used a mouse model of inducible PCs depletion (Math1^Lox/LoxVilCreER^T2) and performed partial portal vein ligation (PPVL) to induce portal hypertension. After 14 days, we performed mRNA sequencing and evaluated the expression of specific lymphangiogenic genes in small intestinal tissue. Intestinal and mesenteric lymphatic vessels proliferation was assessed by immunohistochemistry. Intestinal organoids with or without PCs were exposed to pathogen-associated molecular patterns, and conditioned media (CM) was used to stimulate human lymphatic endothelial cells (LECs). The lymphangiogenic activity of stimulated LECs was assessed by tube formation and wound healing assays. Secretome analysis of CM was performed using label-free proteomics quantification methods. Intestinal immune cell infiltration was evaluated by immunohistochemistry. We observed that the intestinal gene expression pattern was altered by the absence of PCs only in portal hypertensive mice. We found a decreased expression of specific lymphangiogenic genes in the absence of PCs during portal hypertension, resulting in a reduced proliferation of intestinal and mesenteric lymphatic vessels as compared to controls. In vitro analyses demonstrated that lymphatic tube formation and endothelial wound healing responses were reduced significantly in LECs treated with CM from organoids without PCs. Secretome analyses of CM revealed that PCs secrete proteins that are involved in lipid metabolism, cell growth and proliferation. Additionally, intestinal macrophages infiltrated the ileal mucosa and submucosa of mice with and without Paneth cells in response to portal hypertension. Our results suggest that intestinal microbiota signals stimulate Paneth cells to secrete factors that modulate the intestinal and mesenteric lymphatic vessels network during experimental portal hypertension. Full article

(This article belongs to the Special Issue Lymphatic Function and Dysfunction: From Physiopathology to Therapy)

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Other

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7 pages, 1789 KiB

Open AccessCase Report

Lympho-SPECT/CT as a Key Tool in the Management of a Patient with Chylous Ascites

by Francesca Iuele, Dino Rubini, Corinna Altini, Paolo Mammucci and Antonio Rosario Pisani

Biomedicines 2023, 11(2), 282; https://doi.org/10.3390/biomedicines11020282 - 19 Jan 2023

Viewed by 1619

Abstract

Chylous ascites is a rare form of ascites usually associated with cirrhosis, abdominal malignancies, surgeries or infections. We presented a case of chylous ascites after robotic laparoscopic prostatectomy (PLDN-RALP), in which the correct diagnosis was achieved by SPECT/CT lymphoscintigraphy. A 72-year-old male developed chylous ascites after surgery and underwent lymphoscintigraphy with radiolabeled albumin nanocolloids for the supplementary study of the lymph flow and to detect a possible site of leakage. The scintigraphic imaging demonstrated the abdominal effusion and lymph stasis in the left iliac region. The combination of planar imaging with SPECT/CT can resolve the assessment of chylous disorders. Full article

(This article belongs to the Special Issue Lymphatic Function and Dysfunction: From Physiopathology to Therapy)

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17 pages, 1748 KiB

Open AccessSystematic Review

The Effects of Exercise-Based Interventions on Fluid Overload Symptoms in Patients with Heart Failure: A Systematic Review and Meta-Analysis

by Mei Rosemary Fu, Yuan Li, Catherine Conway, Alessandra Masone, Jinbo Fang and Christopher Lee

Biomedicines 2022, 10(5), 1111; https://doi.org/10.3390/biomedicines10051111 - 11 May 2022

Cited by 2 | Viewed by 3178

Abstract

Patients with heart failure are subjected to a substantial burden related to fluid overload symptoms. Exercise can help the lymphatic system function more effectively to prevent fluid build-up in tissues and interstitium, thus potentially mitigating the symptoms due to fluid overload. The objective of this systematic review was to examine the effects of exercise-based interventions on fluid overload symptoms among patients with heart failure. MEDLINE, Embase, Cochrane Library, and CINAHL databases were systematically searched for relevant studies published from inception to August 2021. We included randomized controlled trials that compared exercise-based interventions of different modalities and usual medical care for adult patients with heart failure and reported the effects of interventions on any symptoms related to fluid overload. A random-effects meta-analysis was used to estimate the effectiveness, and a subgroup analysis and univariate meta-regression analysis were used to explore heterogeneity. Seventeen studies covering 1086 participants were included. We found robust evidence indicating the positive effect of exercises in dyspnea relief (SMD = −0.48; 95%CI [−0.76, −0.19]; p = 0.001); the intervention length also influenced the treatment effect (β = 0.033; 95%CI [0.003, 0.063]; p = 0.04). Initial evidence from existing limited research showed that exercise-based intervention had positive effect to alleviate edema, yet more studies are needed to verify the effect. In contrast, the exercise-based interventions did not improve fatigue compared with usual care (SMD = −0.27; 95%CI [−0.61, 0.06]; p = 0.11). Findings regarding the effects of exercises on bodily pain, gastro-intestinal symptoms, and peripheral circulatory symptoms were inconclusive due to limited available studies. In conclusion, exercise-based interventions can be considered as an effective nonpharmacological therapy for patients with heart failure to promote lymph flow and manage fluid overload symptoms. Exercise-based interventions seem to have very limited effect on fatigue. More research should investigate the mechanism of fatigue related to heart failure. Future studies with high methodological quality and comprehensive assessment of symptoms and objective measure of fluid overload are warranted. Full article

(This article belongs to the Special Issue Lymphatic Function and Dysfunction: From Physiopathology to Therapy)

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