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Background: Immunotherapy has shown intracranial efficacy in non-small cell lung cancer (NSCLC) patients with brain metastases. However, predictive biomarkers for intracranial response to immunotherapy are lacking. This post-hoc analysis aimed to explore the potential of immunological cytokines in cerebrospinal fluid (CSF) to predict intracranial tumor response to immunotherapy in patients with brain metastases. Methods: Treatment-naive NSCLC patients with brain metastases who received camrelizumab plus chemotherapy were enrolled. Paired plasma and CSF samples were prospectively collected at baseline and the first treatment assessment. All samples were analyzed for 92 immuno-oncology cytokines using Olink's panels. Results: A total of 28 patients were included in this analysis. At baseline, most immunological cytokines were significantly lower in CSF than in plasma, whereas a subset comprising CD83, PTN, TNFRSF21, TWEAK, ICOSLG, DCN, IL-8, and MCP-1, was increased in CSF. Baseline CSF levels of LAMP3 were significantly higher in patients with intracranial tumor response, while the levels of CXCL10, IL-12, CXCL11, IL-18, TIE2, HGF, and PDCD1 were significantly lower. Furthermore, the CXCL10, CXCL11, TIE2, PDCD1, IL-18, HGF, and LAMP3 in CSF were also significantly associated with intracranial progression-free survival for immunotherapy. The identified cytokines in CSF were decreased at the first treatment evaluation in patients with intracranial tumor response. The logistic CSF immuno-cytokine model yielded an AUC of 0.91, as compared to PD-L1 expression (AUC of 0.72). Conclusions: Immunological cytokines in CSF could predict intracranial tumor response to immunotherapy in NSCLC patients with brain metastases, and the findings warrant validation in a larger prospective cohort study. Trial registration: ClinicalTrials.gov identifier: NCT04211090. [ABSTRACT FROM AUTHOR]

Abstract Yellow grub disease, caused by Clinostomum metacercaria, is an endemic zoonotic infection in freshwater fish, responsible for Halzoun syndrome transmitted through the consumption of raw infected fish. This study aimed to conduct a multidisciplinary investigation integrating detailed morphology, oxidative stress, immunology, and histopathology alteration to advance our understanding of Clinostomum infection. In this annual study, 400 Nile tilapia (Oreochromis niloticus) were collected from the Nile River at Al Bahr Al Aazam, Giza Governorate to assess Clinostomum infection prevalence. Of the examined fish, 160 individuals (40.0%) harboured larval Clinostomum infections. Clinostomum metacercariae were observed in various anatomical locations, with 135 fish (33.8%) in buccal cavities, 21 fish (5.25%) in gill chambers, and 4 fish (1.0%) on the skin. Infection intensity ranged from 2 to 12 cysts per fish, averaging 5 cysts, notably with skin infections characterized by a single cyst in each fish. Macroscopic encysted metacercariae were collected from buccal cavities, gills, and skin. Micro-morphology revealed distinct features in C. complanatum, including an elliptical oral sucker with collar-like rings and large sensory papilla-like structures, contrasting with the absence of these features in C. phalacrocoracis. Oxidative stress, assessed through malondialdehyde (MDA) and nitric oxide levels, revealed an elevation in MDA to 35.13 ± 6 nmol/g and nitric oxide to 25.80 ± 3.12 µmol/g in infected fish. In infected fish, MHC-I gene expression increased approximately 13-fold, MHC-II peaked at 19-fold, and IL-1β significantly upregulated by 17-fold, compared to control levels. Histopathology detailed associated lesions, such as cyst encapsulation and eosinophilic infiltration. Clinstomiasis and its impacts on fish hosts offer crucial insights to control this emerging fish-borne zoonotic disease, threatening wildlife, aquaculture, and human health.

Yellow grub disease, caused by Clinostomum metacercaria, is an endemic zoonotic infection in freshwater fish, responsible for Halzoun syndrome transmitted through the consumption of raw infected fish. This study aimed to conduct a multidisciplinary investigation integrating detailed morphology, oxidative stress, immunology, and histopathology alteration to advance our understanding of Clinostomum infection. In this annual study, 400 Nile tilapia (Oreochromis niloticus) were collected from the Nile River at Al Bahr Al Aazam, Giza Governorate to assess Clinostomum infection prevalence. Of the examined fish, 160 individuals (40.0%) harboured larval Clinostomum infections. Clinostomum metacercariae were observed in various anatomical locations, with 135 fish (33.8%) in buccal cavities, 21 fish (5.25%) in gill chambers, and 4 fish (1.0%) on the skin. Infection intensity ranged from 2 to 12 cysts per fish, averaging 5 cysts, notably with skin infections characterized by a single cyst in each fish. Macroscopic encysted metacercariae were collected from buccal cavities, gills, and skin. Micro-morphology revealed distinct features in C. complanatum, including an elliptical oral sucker with collar-like rings and large sensory papilla-like structures, contrasting with the absence of these features in C. phalacrocoracis. Oxidative stress, assessed through malondialdehyde (MDA) and nitric oxide levels, revealed an elevation in MDA to 35.13 ± 6 nmol/g and nitric oxide to 25.80 ± 3.12 µmol/g in infected fish. In infected fish, MHC-I gene expression increased approximately 13-fold, MHC-II peaked at 19-fold, and IL-1β significantly upregulated by 17-fold, compared to control levels. Histopathology detailed associated lesions, such as cyst encapsulation and eosinophilic infiltration. Clinstomiasis and its impacts on fish hosts offer crucial insights to control this emerging fish-borne zoonotic disease, threatening wildlife, aquaculture, and human health. [ABSTRACT FROM AUTHOR]

The study determined immunological indices of Giant African Land snail (Archachatina marginata) improved with fixed dose of vitamin C under acute heat stress (AHS). Prior to the AHS, vitamin C was administered for four weeks to two treatment groups, while other two treatment groups were not. Each treatment was monitored, haemolymph collected at 0, 30 and 60 minutes exposure times. Immunological cytokines: interferon gamma (IFN-γ) and interleukin 2 (IL-2); and total haemocyte counts (THC) were determined. Under AHS, vitamin C elevated (p 0.05) by vitamin C under AHS. Highest (p 0.05). With fixed dose of vitamin C and exposure time, highest (p

The study determined immunological indices of Giant African Land snail (Archachatina marginata) improved with fixed dose of vitamin C under acute heat stress (AHS). Prior to the AHS, vitamin C was administered for four weeks to two treatment groups, while other two treatment groups were not. Each treatment was monitored, haemolymph collected at 0, 30 and 60 minutes exposure times. Immunological cytokines: interferon gamma (IFN-γ) and interleukin 2 (IL-2); and total haemocyte counts (THC) were determined. Under AHS, vitamin C elevated (p <0.05) IFN-γ production (606.33 ± 302.86) compared to other groups with or without vitamin C administration (7.20 ± 1.58 vs. 73.20 ± 32.23 vs. 7.80 ± 1.36). IL-2 was not affected (p >0.05) by vitamin C under AHS. Highest (p <0.05) THC values was obtained with vitamin C administration under AHS, but reduced under no AHS. Exposure time affected (p <0.05) IFN-γ production and THC values, but not IL-2 (p >0.05). With fixed dose of vitamin C and exposure time, highest (p <0.05) IFN-γ values were obtained under AHS with vitamin C administration at 30 minutes and at 60 minutes in THC, compared to other groups. The study concluded that fixed dose of vitamin C at 150 mg kg-1 of feed was appropriate under AHS to boost the immune system of the animals. [ABSTRACT FROM AUTHOR]

The circadian rhythm is a biological characteristic of living organisms in order to adapt to the natural environment． The clock genes such as Bmal1，Clock，PERs，CRYs，Rev-erbα and clock control genes exert vital function． The interaction between immune cells and bone cells regulates the balance of bone metabolism through the interaction of common cytokines and signaling pathways，and immune disorders could cause abnormal bone metabolism． The birth of osteoimmunology is beneficial to the further study of the interaction between skeletal system and immune system，and osteoimmunology is involved in the occurrence and progression of many orthopedic diseases and immune diseases． In the physiological state，clock genes play an important role in maintaining the balance of osteoimmunology by regulating the circadian rhythm of skeletal system and immune system． However，in the pathological state，clock genes malfunction not only causes the disorders of circadian rhythm of the skeletal system and the immune system，it further leads to loss of bone mass and immuno-inflammatory reactions． It also exerts effects on bone metabolism through osteoimmunology related factors such as IL-1，IL-6，TNF-α and RANKL． The immuno-inflammatory reactions also affect the normal function of clock genes，which in turn affects bone metabolism． According to the characteristics of clock genes and bone metabolism，understanding the interaction between clock genes and osteoimmunology under physiological and pathological conditions will have certain guiding significance for the prevention and treatment of skeletal system diseases and immune system diseases． [ABSTRACT FROM AUTHOR]

Since Arron first introduced the concept of osteoimmunology in Nature,the study of the immune system and skeletal system gradually has become a hot point nationally and internationally. In osteoimmunology,OPG / RANKL / RANK as a main signaling pathway involved in immune regulation of bone metabolism has drawn much attention. During body exercise,mechanical stress and changes of immune function can affect bone metabolism through OPG / RANKL / RANK signaling pathway. Moderate exercise can increase gene expression of OPG,inhibit secretion and gene expression of RANKL,and promote secretion of protective cytokines such as IL-2,IL-18,IFN,etc.,which benefits bone formation and positive balance of bone metabolism. Strenuous longtime exercise and excessive training increase gene expression of RANKL,inhibit gene expression of OPG,improve osteoclast activity,and promote secretion of inflammatory cytokines such as IL-6, TNF, and IL-17, which promote bone absorption indirectly,leading to negative balance of bone metabolism. In order to knowmore about the relationship between exercise,immune,and bone metabolism,this article summarizes the related reports about exercise,immune,and bone metabolism,explores the regulatory mechanism that exercise affects bone metabolism and OPG / RANKL / RANK signaling pathways and the effect of immunological cytokines on OPG / RANKL / RANK signaling pathways when doing exercise,and provides the theoretical foundation for exercise and osteoimmunology research and the prevention of bone metabolic diseases. [ABSTRACT FROM AUTHOR]