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Nonrestrictive diet does not increase infections during post-HSCT neutropenia: data from a multicenter randomized trial.

Infections are a major cause of morbidity and mortality during neutropenia after hematopoietic stem cell transplantation (HSCT). The use of a low-microbial protective diet (PD) in the peritransplantation period is a standard of care, although its efficacy has never been tested prospectively. We conducted a multicenter, randomized, noninferiority trial, enrolling all consecutive adult patients undergoing high-dose induction chemotherapy or HSCT with the objective to compare nonrestrictive diet (NRD) vs PD. Overall, 222 patients were enrolled, randomly assigned, and analyzed. One hundred seventy

The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.

Chemokines are an indispensable component of our immune system through the regulation of directional migration and activation of leukocytes. CXCL8 is the most potent human neutrophil-attracting chemokine and plays crucial roles in the response to infection and tissue injury. CXCL8 activity inherently depends on interaction with the human CXC chemokine receptors CXCR1 and CXCR2, the atypical chemokine receptor ACKR1, and glycosaminoglycans. Furthermore, (hetero)dimerization and tight regulation of transcription and translation, as well as post-translational modifications further fine-tune the s

The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.

The cGAS-STING pathway acts as a critical molecular hub connecting genomic instability with cellular senescence. Functioning as a key regulator of the innate immune system, this pathway detects aberrant cytoplasmic DNA to activate downstream inflammatory responses, thereby playing a pivotal role in aging-related diseases. This review systematically explores the core mechanisms by which the cGAS-STING pathway regulates cellular senescence, emphasizing its role in triggering senescence through the recognition of DNA damage signals (e.g., oxidative stress, telomere dysfunction) and promoting para

Plumbagin, a Biomolecule with (Anti)Osteoclastic Properties.

Plumbagin is a plant-derived naphthoquinone that is widely used in traditional Asian medicine due to its anti-inflammatory and anti-microbial properties. Additionally, plumbagin is cytotoxic for cancer cells due to its ability to trigger reactive oxygen species (ROS) formation and subsequent apoptosis. Since it was reported that plumbagin may inhibit the differentiation of bone resorbing osteoclasts in cancer-related models, we wanted to elucidate whether plumbagin interferes with cytokine-induced osteoclastogenesis. Using C57BL/6 mice, we unexpectedly found that plumbagin treatment enhanced o

The dual balance of the cytokine network: key messengers of immune activation and triggers of cytokine storm.

The cytokine network is the central regulatory system for intercellular communication within the immune system. Its proper function depends on the dynamic balance between pro-inflammatory and anti-inflammatory cytokines. Through complex positive and negative feedback loops, this balance precisely regulates the intensity and duration of immune responses, thereby playing a critical role in both physiological and pathological states. This review systematically summarizes the compositional features and classification framework of the cytokine network, as well as the mechanisms by which it maintain

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… It directly inhibits synthesis of intestinal epithelial tight junction proteins and induces epithelial cells to release chemokines, thereby exacerbating the vicious cycle of bacterial translocation and inflammatory recruitment. …

Роль Гут Микробиота в неврологических, психиатрических и неевроразвитых расстройствах.

АИМ: Эта статья направлена на изучение роли человеческого кишечного микробиота (ГМ) в патогенезе неврологических, психиатрических и нейроразвитых расстройств, с уделением особого внимания его влиянию на здоровье и болезни и изучением потенциальных терапевтических стратегий, ориентированных на модификацию ГМ. МАТЕРИАЛЫ И МЕТОДЫ: Предусмотрен всеобъемлющий анализ состава кишечного микробиота и его взаимодействия с человеческим телом, в частности его роли в неврологических и психиатрических условиях. В обзоре обсуждаются факторы, влияющие на состав ГМ, включая родовой режим, грудное вскармливание

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… Bacterial Translocation from the Gastrointestinal Tract Trends Microbiol. 1995 3 149 154 10.1016/S0966-842X(00)88906-4 7613757 13. Van den Abbeele P. Belzer C. Goossens M. Kleerebezem M. De Vos W.M. Thas O. De Weirdt R. Kerckhof F.-M. Van de Wiele T. … Gut Microbiota, Tight Junction Protein Expression, Intestinal Resistance, Bacterial Translocation and Mortality Following Cholestasis Depend on the Genetic Background of the Host Gut Microbes 2013 4 292 305 10.4161/gmic.24706 23652772 PMC3744514 29. Bäckhed F. Manchester J.K. Semenkovich C.F. …

The Role of the Gut Microbiome in Pathogenesis, Biology, and Treatment of Plasma Cell Dyscrasias.

In response to emerging discoveries, questions are mounting as to what factors are responsible for the progression of plasma cell dyscrasias and what determines responsiveness to treatment in individual patients. Recent findings have shown close interaction between the gut microbiota and multiple myeloma cells. For instance, that malignant cells shape the composition of the gut microbiota. We discuss the role of the gut microbiota in (i) the development and progression of plasma cell dyscrasias, and (ii) the response to treatment of multiple myeloma and highlight faecal microbiota transplantat

Роль микробиомы в множестве миелом: новые знания и терапевтические возможности.

Множественная миелома — гематологический рак, описываемый распространением плазменных клеток в костном мозге, что вызывает иммунную дисфункцию и другие аномалии. Микробиом кишечника, микробное сообщество в желудочно-кишечном тракте, было обнаружено, что он модифицирует системный иммунитет, воспаление и метаболизм. Хотя взаимосвязь между кишечным микробиомом и множеством миелома была обнаружена в недавних исследованиях, существует пробел в знаниях, связывающий воздействие микробиома на патогенез и лечение множественной миеломы. Несбалансированность в кишечном микробиоме, дисбиозе, может влиять

The interplay of CD150 and CD180 receptor pathways contribute to the pathobiology of chronic lymphocytic leukemia B cells by selective inhibition of Akt and MAPK signaling.

Cell surface expression of CD150 and CD180 receptors in chronic lymphocytic leukemia (CLL) associates with mutational IGHV status and favourable prognosis. Here we show a direct correlation between cell surface expression and colocalization of these receptors on CLL B cells. In the absence of CD150 and CD180 on the cell surface both receptors were expressed in the cytoplasm. The CD150 receptor was colocalized with markers of the endoplasmic reticulum, the Golgi apparatus and early endosomes. In contrast, CD180 was detected preferentially in early endosomes. Analysis of CD150 isoforms different

Время отключения в слоях при мукозите и его ассоциация с системными осложнениями у пациентов с пересадкой гематопоэтических стволовых клеток: выводы из национального исследования в стационаре.

ОБЪЕКТ ИССЛЕДОВАНИЯ: Оральные узловатые мукозные инфекции (ОУМИ) являются частой и серьезной осложнением трансплантации гемопоэтических клеток (ТГК). Определено ли то, что длительное время выписки из больницы, используемое как прокси для увеличенного срока пребывания (СПП), идентифицирует большую системную морбидность у пациентов, которые развивают ОУМИ, остается неясным. Настоящее ретроспективное когортное исследование направлено на оценку, у пациентов с документированным ОУМИ среди получателей ТГК, длительное время выписки независимо связано с увеличением системных осложнений.МЕТОДЫ: Настоящ

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… In contrast, ulcerative mucositis (grades 3–4) breaches epithelial integrity, serving as a direct portal for bacterial translocation during neutropenia—a key driver of septicemia, healthcare-associated infections, and secondary organ dysfunction [ 33 , 34 ]. … This approach was chosen because ulcerative mucositis constitutes the biologically and clinically most relevant phenotype, directly disrupting the mucosal barrier and facilitating bacterial translocation during neutropenia. …

Эффективность интенсивной антиэпидемиологической терапии, включая оланзапин у нескольких пациентов миэломы, лечившихся высокодозированными мелфаланами с аутологической трансплантацией стволовых клеток.

ЦЕЛЬ: Кондиционирование с использованием высокодозированного мелфалана (MEL), за которым следует аутологическая трансплантация стволовых клеток (ASCT), является стандартным методом лечения множественной миеломы (MM). Оптимальный режим предотвращения тошноты и рвоты, вызванных химиотерапией, не ясен. Мы стремились ретроспективно оценить антиеметический эффект и безопасность four- интенсивный наркологический режим, включая оланзапин (ОЛА) на CINV у пациентов MM, получающих MEL/ASCT. МЕТОДЫ: МЕЛ200 мг/м2) в дневное время 1, за которым следует ASCT в день 3. Пациенты были отнесены к стандартной гр

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… Relative to oral and enteral nutrition, the use of TPN is associated with reduced gastrointestinal integrity, increased risk of central venous catheter infection, and bacterial translocation [ 36 ]. … Bacterial translocation and enteral nutrition in humans: an outsider looks in. JPEN J Parenter Enteral Nutr. 1995;19(2):156–65. 10.1177/0148607195019002156 37. …

Research advances in peptide‒drug conjugates.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, link

Myeloid-Derived Suppressor Cells in Sepsis: Pathophysiology, Duality, and Therapeutic Frontiers.

Sepsis-induced immunosuppression, one of the factors contributing to mortality, is closely mediated by myeloid-derived suppressor cells (MDSCs). This review first outlines MDSC biology, describing their origin from pathological emergency myelopoiesis and classification into polymorphonuclear and monocytic subsets. We then discuss their dual role: an early, protective modulation of cytokine storm that later evolves into harmful immunosuppression associated with secondary infections and death. The underlying mechanisms involve L-arginine depletion ( via arginase 1/inducible nitric oxide synthase

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… Indirect modulation | Probiotics/FMT | GI Disorders | Preclinical/Early Clinical | Risk of bacterial translocation in immunocompromised patients with permeable gut barriers. …

A Systematic Review Evaluating the Impact of Fibre Supplementation on Gut Health and Other Clinical Outcomes in Adults with Haematological Malignancies During Haematopoietic Stem Cell Transplantation.

Background: Gut health is often disrupted in adults with haematological malignancies (HMs) receiving chemotherapy and haematopoietic stem cell transplantation (HCT). Microbial diversity is reduced, and both infection risk and inflammation increased. The role of dietary fibre in enhancing gut health, immune regulation, reducing complications, and improving clinical outcomes for people with HMs shows promise but the extent of their role remains unclear. Objectives: This systematic review evaluated the role of dietary fibre supplementation in adults with HMs undergoing HCT on gut health, immune f

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… SCFAs, especially butyrate, strengthen tight junctions between intestinal cells, supporting gastrointestinal integrity and reducing bacterial translocation and infection risk [ 23 ]. …

Phase 2 study of natalizumab plus standard corticosteroid treatment for high-risk acute graft-versus-host disease.

Graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract is the main cause of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation. Ann Arbor (AA) scores derived from serum biomarkers at onset of GVHD quantify GI crypt damage; AA2/3 scores correlate with resistance to treatment and higher NRM. We conducted a multicenter, phase 2 study using natalizumab, a humanized monoclonal antibody that blocks T-cell trafficking to the GI tract through the α4 subunit of α4β7 integrin, combined with corticosteroids as primary treatment for patients with new onset AA2/3 GV

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… Severe GI GVHD increases the risk for bacterial translocation, which can result in severe infections, 39 , 40 , 41 as occurred in this study. …

Salmonella enterica and outer membrane vesicles are current and future options for cancer treatment.

Conventional cancer therapies have many limitations. In the last decade, it has been suggested that bacteria-mediated immunotherapy may circumvent the restrictions of traditional treatments. For example, Salmonella enterica is the most promising bacteria for treating cancer due to its intrinsic abilities, such as killing tumor cells, targeting, penetrating, and proliferating into the tumor. S. enterica has been genetically modified to ensure safety and increase its intrinsic antitumor efficacy. This bacterium has been used as a vector for delivering anticancer agents and as a combination thera

Towards Drug Repurposing in Cancer Cachexia: Potential Targets and Candidates.

As a multifactorial and multiorgan syndrome, cancer cachexia is associated with decreased tolerance to antitumor treatments and increased morbidity and mortality rates. The current approaches for the treatment of this syndrome are not always effective and well established. Drug repurposing or repositioning consists of the investigation of pharmacological components that are already available or in clinical trials for certain diseases and explores if they can be used for new indications. Its advantages comparing to de novo drugs development are the reduced amount of time spent and costs. In thi

Pseudomonas otitidis Bacteremia in a Patient with Cancer during the Palliative-care Phase.

Pseudomonas otitidis bacteremia is rare. We herein report a case of bacteremia caused by P. otitidis in a patient with advanced appendiceal cancer. A 79-year-old Japanese man developed infection when he was admitted to our hospital for palliative care. Blood culture revealed the presence of Pseudomonas spp. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to identify the organism accurately. The patient was treated with a two-week course of piperacillin/tazobactam, and the bacteremia was successfully controlled. Clinicians should be aware that P. otitidis c

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… Whether the infection is community-acquired or healthcare-associated thus remains unclear; however, a gastrointestinal source of bacterial translocation is a possible consideration. It is important to recognize that P. otitidis can cause bacteremia in immunocompromised patients. …

Mechanism and therapeutic potential of traditional Chinese medicine extracts in sepsis.

Sepsis is a complex syndrome characterized by multi-organ dysfunction, due to the presence of harmful microorganisms in blood which could cause mortality. Complications associated with sepsis involve multiple organ dysfunction. The pathogenesis of sepsis remains intricate, with limited treatment options and high mortality rates. Traditional Chinese medicine (TCM) has consistently demonstrated to have a potential on various disease management. Its complements include reduction of oxidative stress, inhibiting inflammatory pathways, regulating immune responses, and improving microcirculation. Tra

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… During severe infections like septicemia, stress weakens or damages intestinal barrier function, allowing a significant influx of bacteria and endotoxins into circulation via the portal vein and intestinal lymphatic system, resulting in gut-derived endotoxemia and bacterial translocation. …

Diabetes Insipidus: A Pragmatic Approach to Management.

Diabetes insipidus (DI) is a disorder of water balance characterized by polyuria and polydipsia. It can occur due to genetic and acquired causes that affect the secretion or action of arginine vasopressin (AVP) or antidiuretic hormone (ADH).Markedly increased thirst and urination are not only quite distressing but also increases the risk of volume depletion and hypernatremia in severe situations. A careful diagnosis of the type of DI and its etiology is based on careful clinical evaluation, measurement of urine and serum osmolality, and water deprivation test. Management includes the correctio