Histopathological Inflammation Research Articles

CIP2A inhibitors TD52 and Ethoxysanguinarine promote macrophage autophagy and alleviates acute pancreatitis by modulating the AKT-mTOR pathway

BackgroundAcute pancreatitis (AP) is a prevalent and serious condition within the digestive system, with approximately 20 % to 30 % of cases advancing to severe acute pancreatitis (SAP). During the initial phases of SAP, macrophages are activated in response to the substantial amounts of acinar cell contents and damage-associated molecular patterns (DAMPs) resulting from acinar cell destruction. Subsequently, activated macrophages release a significant array of pro-inflammatory factors that exacerbate the progression of SAP. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogenic protein that is intimately linked to immune regulation. While the role of CIP2A in T-cell-mediated specific immune responses has been reported, its function and mechanism in macrophages, a component of non-specific immunity, have not been widely studied. This research fills this knowledge gap by elucidating the critical role of CIP2A in regulating macrophage autophagy and inflammation. This finding not only expands our understanding of CIP2A in immune modulation but also provides a new scientific basis and potential application prospects for targeting CIP2A in the treatment of AP. MethodsWe established AP using a combination of palmitoleic acid with anhydrous ethanol or using caerulein alone. The effects of TD52 and Ethoxysanguinarine (Etho) on SAP were evaluated through serological, histopathological, and tissue inflammation observations. The effect of TD52 on macrophage activation in vitro was examined using primary macrophages (PMs) and RAW264.7 cells. ResultsWe found that TD52 and Etho inhibit CIP2A expression while reducing the levels of serum amylase, lipase, and inflammatory cytokines, thereby alleviating the pathological symptoms of SAP. Additionally, TD52 could reduce the infiltration of macrophages into pancreatic tissue. Therefore, we established a model of macrophage inflammatory response mimicking the pathophysiological process of AP and detected changes in inflammation, apoptosis, and autophagy through pre-treatment of macrophages with TD52. The results show that inhibiting CIP2A expression decreases the release of inflammatory cytokines and reduces apoptosis in macrophages. Further exploration revealed that TD52 promoted macrophage autophagy regulation and inhibited the AKT-mTOR pathway to modulate macrophage activation. ConclusionIn summary, our findings indicate that TD52 and Etho can alleviate the severity of SAP. TD52 can block the AKT-mTOR pathway to promote macrophage autophagy, thereby improving SAP. Thus, CIP2A may serve as one of the molecular targets in SAP, highlighting its potential as a therapeutic option.

Evaluation of pathways involved in the protective effect of trans sodium crocetinate against contrast-induced nephropathy in rats.

Contrast-induced nephropathy (CIN) is the most important side effect following contrast media application. The purpose of this study was to investigate the nephroprotective effects of trans sodium crocetinate (TSC) against sodium amidotrizoate/meglumine amidotrizoate (SAMA).Wistar rats were classified into eight groups (n = 6, male, 220-250g) including (1) sham, injection of solvents (intraperitoneally; i.p.), (2) premedication-control, N(ω)-nitro-L-arginine methyl ester (L-NAME, 10mg/kg, i.p.) + indomethacin (IND, 10mg/kg, i.p.), (3) model (L-NAME + IND + SAMA (12.5ml/kg, i.p.)), (4-6) TSC 10, 20, and 40mg/kg/day, 7 days, i.p., and L-NAME + IND + SAMA, (7) N-acetylcysteine (NAC, 125mg/kg/day, 7 days, i.p.) and L-NAME + IND + SAMA, (8) TSC alone (40mg/kg/day, 7 days, i.p.). Rats were injected with L-NAME, IND, and SAMA 40h after water deprivation.SAMA caused the enhancement of histopathological damage in kidney tissue, biochemical factors (serum blood urea nitrogen and creatinine), and oxidative stress. Moreover, SAMA increased inflammation (TNF-α), apoptosis proteins(Caspase 3-cleaved and Bax/Bcl-2 ratio), and autophagy markers (Beclin-1 and LC3 II/I ratio). TSC declined biochemical factors and oxidative stress. Also, TSC 40mg/kg decreased histopathological damage, inflammation, apoptosis, and autophagy markers.This study demonstrated that TSC has nephroprotective effects through anti-oxidant, anti-inflammatory, and anti-apoptotic properties, as well as regulating autophagy.

Polyhexamethylene Guanidine Phosphate Induces Restrictive Ventilation Defect and Alters Lung Resistance and Compliance in Mice.

Polyhexamethylene guanidine phosphate (PHMG-p), a major ingredient of humidifier disinfectants, is known to induce inflammation, interstitial pneumonitis, and fibrosis in the lungs. While its histopathologic toxicities have been studied in rodents, research on pulmonary function test (PFT) changes following PHMG-p exposure is limited. This study aimed to investigate the acute and chronic effects, as well as the dose and time response, of PHMG-p on the lungs in mice using PFT and histopathologic examinations. In the single instillation model, mice received PHMG-p and were sacrificed at 2, 4, and 8 weeks. In the five-time instillation model, PHMG-p was administered five times at one-week intervals, and mice were sacrificed 10 weeks after the first instillation. Results showed that PHMG-p exposure reduced lung volume, increased resistance, and decreased compliance, indicating a restrictive ventilation defect. Histopathologic examination showed increases in lung inflammation and fibrosis scores. Changes in several lung volume and compliance parameters, as well as histopathology, were dose-dependent. Lung resistance and compliance parameters had significant correlations with lung inflammation and fibrosis scores. PHMG-p exposure in mice resulted in a restrictive ventilation defect with altered lung resistance and compliance, along with histopathologic lung inflammation and fibrosis.

Bovine Lactoferrin Mitigates Oxidative Stress and Inflammation in CCL4 and High-fat Diet-induced NAFLD in C57BL/6 Mice

Background: Impacting approximately 20-30% of adults, nonalcoholic fatty liver disease (NAFLD) is the leading contributor to liver dysfunction. This condition is characterized by the accumulation of more than 5% fat in the liver without the presence of concurrent chronic liver diseases or alcohol abuse. NAFLD manifests across a spectrum ranging from simple steatosis to more complex forms involving hepatic lesions, inflammation and fibrosis. This research aimed to assess the therapeutic effectiveness of Bovine Lactoferrin (BLF) in a model of NAFLD using male C57BL/6 mice. Methods: Adult male C57BL6 mice, with an average weight of 28 g, were obtained and maintained in a consistent environment at 22±2oC for 6 weeks, following a regulated 12-hour light-12-hour dark cycle. Control groups 1 and 3 were provided with a standard pellet feed, while model groups 2, 4, 5 and 6 were supplied with a high-fat diet. Induction of NAFLD included administering a high-fat diet (HFD) and CCl4 (0.5 mg/kg with olive oil) twice a week via intraperitoneal injection over 6 weeks. After the experimental procedures, an assessment of serum-biochemical parameters, inflammatory cytokines, anti-oxidant profile and liver histopathology were conducted. Result: The results revealed significant (p less than 0.05) alteration in sero-biochemical parameters, inflammatory cytokines (IL-10, TNF-α, NF-kB and TGF-β) anti-oxidant profile (nitric oxide assay, TBARS, SOD, GSH and Catalase) and histopathology of group 2 as compared to other groups. The groups 4, 5 and 6 showed significant improvement in all the parameters compared to disease control. The findings from this study suggest that BLF could potentially function as a therapeutic intervention for mitigating hepatic injury, inflammation and fibrosis in NAFLD by deactivating NF-kB pathway.

Immunoexpression of CD34, CD68 and CD3 in Cadmium-Induced Liver Damage and Protective Effectiveness of Bee Bread (Perga)

Cadmium (Cd) is one of the potent environmental toxicants that causes oxidative stress in many organs of the body, including the liver. Perga (bee bread) is used for apitherapeutic purposes due to its medicinal properties. This study was conducted to investigate the effectiveness of perga on endothelial damage and inflammatory cell activation in the liver as a result of exposure to Cd. For this purpose, 32 male Wistar rats (8 rats/group) were randomly divided into 4 groups, as the control, perga (0.5 g/kg of perga), Cd (5 mg/kg of CdCl2), and Cd + perga (0.5 g/kg of perga + 5 mg/kg of CdCl2) groups. Daily intragastric Cd and/or perga was administered for 4 weeks. At the end of the study, the rats were euthanized and liver tissue sections were taken and stained with hematoxylin-eosin and Masson’s Trichrome. Immunohistochemically, the reactivity of the liver sinusoidal endothelium was determined using CD34, the reactivity of the Kupffer cells was determined using CD68, and the levels of T-lymphocyte cells were determined using CD3 antibodies. Exposure to Cd caused significant histological changes in the liver. Immunohistochemically, exposure to Cd caused an increase in the expressions of CD34, CD68, and CD3. On the other hand, the cotreatment of Cd and perga caused partial improvement in some histopathological changes. Compared to the Cd group, there was a decrease in CD34 and CD68 positivity in the Cd + perga group, while no significant difference was detected in the number of CD3-positive cells between the groups. The results revealed that the histopathological changes and inflammation in the rat liver could partially improve with perga supplementation.

The impact of vitamin D3 administration and of high fat diet on oxidative stress and inflammation in experimentally induced polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is commonly associated with obesity and may be exacerbated by the lack of vitamin D3. The study aimed to investigate the effects of vitamin D3 administration in female rats with PCOS and prolonged high fat diet (HFD). Forty-four female Wistar rats, 180-200 g, 10 weeks old, were randomly allocated into 2 groups (n=22) that received a single dose intramuscular injection of: sesame oil (group I), or estradiol valerate (5 mg) in sesame oil (group II). After 4 weeks, intraovarian cysts developed in group II, as evidenced by ultrasonography. In the next step, half of rats from each group received standard diet (SD) and the other half high fat diet, through oral gavage, for 17 weeks, the following groups being obtained: Control (SD), HFD, PCOS (PCOS+SD) and PCOS+HFD. Next, all the rats received, for 5 weeks, 500 UI/kg/day vitamin D3, through oral gavage. Lipid peroxidation was assessed through malondialdehyde level in the ovary and periovarian tissue and the inflammation was quantified in ovary by NFkB, pNFkB, NRF2 and SOD1 expressions. Ovaries from all groups were collected for histopathological analysis. Blood samples were taken to evaluate the basal insulin, triglycerides and total cholesterol levels throughout the experiment. Both groups with PCOS recorded significant increases of malondialdehyde in ovaries (p<0.001) and in periovarian tissue, especially in PCOS+HFD (p<0.05), even after vitamin D3 administration. PCOS+HFD group treated with vitamin D3 showed a high degree of inflammation in ovarian histopathology but with decreased pNFkB expression (p<0.01) while PCOS group recorded an increased SOD1 expression (p<0.05). Additionally, vitamin D3 treatment attenuated the insulin level (p<0.001) in PCOS and in HFD groups and the total cholesterol level in PCOS+HFD group, but triglycerides recordings were without statistical significance (p>0.05). HFD induced inflammation in ovaries, evidenced histologically and through increases of COX2 expressions (p<0.05) without significant influences on oxidative stress and on cholesterol levels. Polycystic ovary syndrome is associated with oxidative stress and inflammation in the ovary tissue and in blood with increased levels of insulin, total cholesterol and triglycerides that might be partially mitigated by vitamin D3 oral administration.

Does complete resection of infected bone improve clinical outcomes in patients with diabetic foot osteomyelitis?

The objective of the study was to compare outcomes in patients with complete surgical resection versus partial resection of diabetic foot osteomyelitis (OM). A post hoc analysis of 171 patients with OM was performed using data from two randomized clinical trials. OM was confirmed with bone culture or histopathology. Surgical culture specimens were obtained from resected bone and sent for histopathology and microbiology. Residual osteomyelitis (RO) was defined as a positive resected margin on culture or histopathology. No residual osteomyelitis (NRO) was defined as no growth from bone culture and no histopathological inflammation in the biopsy of the resection margin. Data from the 12-month follow-up were used to determine clinical outcomes. During the index hospitalization, NRO patients had significantly shorter duration of antibiotic therapy (NRO 21.0, 13.0-38.0 vs. RO 37.0, 20.8-50.0, p <0.01) and more amputations than patients with RO (NRO 89.9% vs. RO 60.9%, p <0.01). During the 12-month follow-up, patients with NRO also had significantly shorter duration of antibiotic therapy (NRO 42, 21.0-66.5 vs. RO 50.5, 35.0-75.0, p = 0.02). During the 12-month follow-up, there was no difference in ulceration at the same site (NRO 3.7%, RO 4.3% p = 0.85), hospitalization (NRO 32.6%, RO 34.8%, p = 0.76), total re-infections (NRO 25.3%, RO 29.3%, p = 0.56), re-infection with osteomyelitis (NRO 13.3% vs. 13.5%, p = 0.36), amputation (NRO 8.8%, RO 5.4%, p = 0.86) and time to wound healing in days (NRO 94, 41.0-365 vs. RO 106, 42.8-365, p = 0.77). Successful treatment of osteomyelitis was achieved by 86.7% and 86.5% of patients. During the index hospitalization, patients with no residual osteomyelitis had more amputations and were treated with antibiotics for a shorter duration. During the 12-month follow-up, patients with no residual osteomyelitis had shorter durations of antibiotics. There were no differences in re-infection, amputation, re-ulceration or hospitalization. Level of evidence: 1.

Development of a Short-Term Embolic Agent Based on Cilastatin for Articular Microvessels.

Background and Objectives: This study aimed to develop an embolic agent with short-term embolic effects using cilastatin as the basic material. Materials and Methods: The particle size distribution of 25 mg cilastatin-based short-term embolic agents was evaluated microscopically under three different mixing conditions. A total of thirty-six healthy male Sprague Dawley rats were divided into four groups. Each group of six rats was injected once into the tail artery with 0.4 mL each of (A) Cilastatin + D-Mannitol Mixture, (B) Iohexol, (C) Prepenem, and (D) embolization promoter (EGgel). Results: A visual inspection of the tail appearance of rats in each group was performed at 0, 3, 7, 15, and 21 days. At weeks 1 and 3, three rats per group were euthanized, and histopathological analyses were performed on the specimens obtained from each group. No significant differences were observed on day 7, but mild inflammation was observed in Group (D) on day 15. Histopathological inflammation scoring of tail central artery embolization was performed using a six-point scale (from 0 = absent to 5 = marked inflammation). Three groups were formed consisting of six male New Zealand white rabbits each: control, positive control, and test groups. The control group received an Iohexol injection (rabbits: 0.8 mL). The positive control and experimental groups were injected with prepenem and cilastatin/D-mannitol compound, respectively (0.8 mL), and vascular angiography was performed. The order of occlusion progression after embolization was as follows: test group, positive control group, and control group. Conclusions: We developed a cilastatin/D-mannitol compound that exhibits characteristics of short-term embolization by utilizing the pharmacokinetic properties of cilastatin and the crystalline material D-mannitol. We evaluated its particle size distribution microscopically, conducted histopathological evaluation including inflammation via animal experiments, and assessed the embolization effect.

Potential Antiallergic Activity of Two Chemically/Enzymatically-Modified Natural Products Against Active Atopic and Systemic Anaphylaxes in CD1 Mice Models

ABSTRACT Introduction Anaphylaxis is a globally increasing allergic reaction that is often fatal. Recently, our previous study reported the possibility of using the modified natural products “sodium R-lipoate (NaRLA) and enzymatically modified isoquercitrin (EMIQ)“ as potential novel safe agents against the non-immunological-degranulation of mast cells. Methods Here, we extended our previous findings by determining the antianaphylactic activity of 50 and 100 mg/kg body weight of NaRLA and EMIQ (given orally and prior to local or systemic challenge) in mice models of ovalbumin (OVA)-induced IgE-dependent active cutaneous anaphylaxis (ACA) and active systemic anaphylaxis (ASA) in comparison with sulfasalazine (SSZ, amast cell stabilizer). Results The pre-treatment of mice with NaRLA or EMIQ completely succeeded, as SSZ, in suppression of the increased vascular permeability associated with IgE-dependent ACA and protected the OVA-sensitized mice from fatal ASA by reducing (p < .001) the skin mast cell degranulation, the elevated peritoneal histamine and interleukin-4 levels, along with decreasing the associated sever gastrointestinal and lung histopathological alterations and inflammation. The high dose of EMIQ prevented death in 70% of mice with anaphylactic shock, better than SSZ. Discussion Our data indicated that NaRLA and EMIQ may be potential prophylactic and therapeutic candidates for the alleviation of atopic and systemic anaphylaxis.

Microplastic in Gastric Fasting Liquid and Associated Gastric Pathology.

To determine the presence of microplastics in the stomach, and the relationship between pathological changes in stomach tissue and microplastics. An analytical study. Place and Duration of the Study: Department of Internal Medicine, Sorgun State Hospital, Yozgat, Turkiye, from December 2022 to November 2023. Fasting gastric fluid sampling and endoscopic sampling including mucosal and submucosal layers from the antrum were performed. The pH values of the gastric fluids were recorded. Samples were analysed gradually by adding iron solution, hydrogen peroxide, and sodium chloride (NaCl) in a beaker at 75 degrees for 30 minutes. Biopsy materials obtained from antrum were examined histopathologically and reported according to the Sydney classification. The relationship between gastric biopsy results and the presence of microplastic was evaluated using Chi-square test. The significance level was taken as p <0.005. The study included 61 individuals. The presence of microplastics was detected in 17 (27.86%) gastric fluid samples obtained from the individuals. A significant correlation was found between increased activity and inflammation in antrum biopsy and the presence of microplastic (χ2 = 8.55 p = 0.014; χ2 = 25.75, p = 0.001). The relationship between atrophy, metaplasia, and Helicobacter pylori in gastric tissue and the presence of microplastic was statistically insignificant (p >0.05). Microplastics were detected in gastric fasting fluid. These materials can cause histopathologic changes and inflammation in the gastric antrum. H. pylori, Intestinal metaplasia, Inflammation, Microplastic, Plastic, Sydney classification.

Linalool may have a therapeutic effect on cadmium-induced nephrotoxicity by regulating NF-κB/TNF and GRP78/CHOP signaling pathways

Cadmium (Cd) is an environmental pollutant heavy metal with nephrotoxic effect. One of the primary constituents of essential oils is Linalool (Lin), a monoterpene having a variety of pharmacological properties including antimicrobial, anti-inflammatory, and antioxidant effects. The purpose of this study was to ascertain how Lin affected endoplasmic reticulum stress (ERS) and pro-inflammatory mediators in Cd-induced nephrotoxicity. In the experiment, 28 male rats were randomly divided into four equal groups as control (no application), Cd (Cd at a dose of 3 mg/kg for the first 7 days), Cd+Lin (Cd at a dose of 3 mg/kg for the first 7 days and 100 mg/kg/day Lin) and Lin (100 mg/kg/day Lin) (n=7). The experiment was completed on the 15th day after all treatments were performed. Blood serum and kidney tissue samples were used for analyses. Cd-induced histopathological changes, inflammation, oxidative stress, and apoptosis were determined to increase in kidney tissue. However, it was observed that Cd-induced adverse effects in kidney tissue were mainly eliminated by Lin treatment. In conclusion, Lin demonstrated anti-inflammatory, anti-oxidant and anti-apoptotic effects in Cd-induced nephrotoxicity. Therefore, we believe that Lin may represent a high potential therapeutic strategy against renal tissue damage.

KGF-2 ameliorates UVB-triggered skin photodamage in mice by attenuating DNA damage and inflammatory response and mitochondrial dysfunction.

Long-term exposure to UVB induces DNA damage, inflammatory response, mitochondrial dysfunction, and apoptosis in skin cells, thus causing skin photodamage. Research has demonstrated the noteworthy antioxidant, anti-inflammatory, DNA repair, and mitochondrial protective properties of keratinocyte growth factor-2 (KGF-2). To examine the impact of KGF-2 on UVB-triggered skin photodamage in mice, hair-removed mice were initially exposed under UVB radiation and subsequently treated with KGF-2 hydrogel and repeated for 6 days. On day 7, the assessment of histopathological alterations, inflammation, DNA damage, mitochondrial function, and apoptosis in mouse skin was assessed. It was found that KGF-2 could effectively relieve cutaneous photodamage symptoms and inhibit epidermal proliferation in mice. Meanwhile, KGF-2 was found to significantly reduce DNA damage, attenuate the inflammatory response, and inhibit the mitochondria-mediated intrinsic apoptotic pathway in the UVB-exposed mouse skin photodamage model. To summarize, our results indicated that KGF-2 reduces the severity of mouse skin photodamage caused by UVB rays by attenuating DNA damage and the inflammatory response, besides inhibiting the mitochondria-mediated intrinsic apoptosis pathway.

Ferroptosis is involved in quercetin-mediated alleviation of Ochratoxin A-induced kidney damage

Ochratoxin A (OTA) induces kidney damage in animals and humans. Ferroptosis is an iron-dependent form of regulated cell death that is involved in OTA-induced kidney injury. Quercetin (QCT), which is commonly found in numerous fruit and vegetables, has extensive pharmacological properties, such as anti-oxidant and anti-inflammatory. The present study aimed to evaluate the effects of QCT on OTA-induced kidney damage and the associated ferroptosis mechanism in mice. The results showed that OTA induced kidney damage, as demonstrated by the presence of kidney histopathological lesions, increased serum BUN and CRE levels, mRNA levels of Ntn1, Kim1, Tnfa, Ilb and Il6, and immunofluorescence of TNFα. OTA induced lipid peroxidation and ferroptosis by increasing the MDA level, 4-HNE production, and the iron concentration, decreasing the GSH content, increasing ACSL4 and HO-1 mRNA and protein levels, and decreasing GPX4 mRNA and protein levels. QCT supplementation alleviated OTA-induced kidney damage and inhibited OTA-induced lipid peroxidation and ferroptosis by reversing the OTA-induced above changes. Erastin weakened the protective effects of QCT on the histopathological damage, renal function, and inflammation induced by OTA. These findings indicated that QCT alleviated OTA-induced kidney injury through ferroptosis, suggesting that QCT might serve as a feed additive in mycotoxin contamination environments.

Protection against α-Amanitin-induced liver toxicity: Efficacy of pomegranate seed oil and black cumin oil

The consumption of mushrooms containing α-Amanitin (α-A) can lead to severe liver damage. In this study, toxicological experiments were conducted to confirm the protective effects of pomegranate seed oil (PSO) and black cumin oil (BCO) against α-A-induced hepatotoxicity. Rats exposed once to α-A (3 mg/kg bw, i.p.) or saline alone (0.1 ml, i.p.) were either left untreated or treated with PSO or BCO at a dose of 2 ml/kg bw/day by oral gavage on the same day, and the treatment was continued for 7 days. Serum aminotransferases (ALT and AST), alkaline phosphatase (ALP) and total protein levels were measured and the active caspase 3 (cl-caspase 3) was evaluated by western blotting in the liver. Serum ALT, AST and ALP levels tended to decrease in the α-A exposed group, but no statistically significant difference was found compared to the saline group (p > 0.05). PSO and BCO did not affect serum liver function tests in rats exposed to saline or α-A. α-A toxicity was demonstrated by a significant decrease in serum total protein level (p < 0.05), a significant increase in liver cl-caspase 3 expression (p < 0.05), and structural liver damage mainly characterized by mononuclear inflammation and steatosis. When α-A exposed rats were treated with BCO, the increase in cl-caspase 3 was not inhibited, on the contrary BCO increased cl-caspase 3 in healthy rats (p < 0.05). PSO significantly ameliorated α-A-induced cl-caspase 3 increase and inflammatory histopathology in the liver. Both PSO and BCO completely prevented α-A-induced protein degradation. The findings indicate that PSO and BCO may protect liver functions against α-A-induced hepatotoxicity, encouraging future comprehensive studies to test them at different doses and frequency.

Raspberry Ketone Attenuates Hepatic Fibrogenesis and Inflammation via Regulating the Crosstalk of FXR and PGC-1α Signaling.

Hepatic fibrosis is a compensatory response to chronic liver injury and inflammation, and dietary intervention is recommended as one of the fundamental prevention strategies. Raspberry ketone (RK) is an aromatic compound first isolated from raspberry and widely used to prepare food flavors. The current study investigated the hepatoprotection and potential mechanism of RK against hepatic fibrosis. In vitro, hepatic stellate cell (HSC) activation was stimulated with TGF-β and cultured with RK, farnesoid X receptor (FXR), or peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) agonist or inhibitor, respectively. In vivo, C57BL/6 mice were injected intraperitoneally with thioacetamide (TAA) at 100/200 mg/kg from the first to the fifth week. Mice were intragastrically administrated with RK or Cur once a day from the second to the fifth week. In activated HSCs, RK inhibited extracellular matrix (ECM) accumulation, inflammation, and epithelial-mesenchymal transition (EMT) process. RK both activated FXR/PGC-1α and regulated their crosstalk, which were verified by their inhibitors and agonists. Deficiency of FXR or PGC-1α also attenuated the effect of RK on the reverse of activated HSCs. RK also decreased serum ALT/AST levels, liver histopathological change, ECM accumulation, inflammation, and EMT in mice caused by TAA. Double activation of FXR/PGC-1α might be the key targets for RK against hepatic fibrosis. Above all, these discoveries supported the potential of RK as a novel candidate for the dietary intervention of hepatic fibrosis.

Placental chronic inflammatory histopathology and fetal growth in a cohort with universal placental examination

IntroductionChronic placental inflammation is a routinely diagnosed group of placental lesions that reflect immunologic dysfunction of the mother, fetus, or both. MethodsComplete placental pathology examinations were performed for all term births at New York Presbyterian- Brooklyn Methodist Hospital from January 2010–August 2016. Diagnoses were blinded except to gestational age. CPI lesions were marked as chronic choriodeciduitis, decidual plasma cells, chronic inflammation of basal plate with anchoring villitis, and chronic villitis. ResultsIn this cohort of term pregnancies, 257 (11.6 %) males and 218 (9.8 %) females had ≥1 CPI lesions. Chronic villitis was the most common (319 or 14 %), with chronic choriodeciduitis, decidual plasma cells, and chronic inflammation of basal plate with anchoring villitis in 94 (4 %), 69 (3 %) and 170 (8 %), respectively. In males, chronic villitis was associated with lower gestational adjusted birthweight and had no association with placental weight. In females, chronic villitis was associated with lower gestational adjusted birthweight, but the effect became nonsignificant after adjustment for placental weight. DiscussionIn summary, CPI lesions’ incidence and association with birth weight vary by sex. Chronic villitis is associated with lower birthweight in females; this effect is completely mediated by placental weight. Chronic villitis showed a weak direct association of chronic villitis in males, but no association with lower placental weight in males. We suggest that differences between our results and previous publications reflect effects of sampling bias.

It is not the best option to perform transurethral enucleation of the prostate immediately after biopsy in patients with histological inflammation.

This study seeks to investigate the impact of histopathological evidence of histological prostatic inflammation (PI) on the surgical outcomes of patients with benign prostatic hyperplasia (BPH) undergoing transurethral bipolar enucleation of the prostate (BiLEP) after biopsy. We conducted a prospective study in which data were collected from 112 patients with BPH who underwent BiLEP immediately after prostate biopsy at the Department of Urology in our hospital between October 2020 and October 2023. This cohort included 52 patients with histopathological prostatic inflammation (BPH + PI group) and 60 patients with simple BPH (BPH group). Baseline characteristics, surgical details, International Prostate Symptom Score (IPSS), quality of life (QoL), post-void residual volume (PVR), maximum flow rate (Qmax), International Index of Erectile Function-5 (IIEF-5), postoperative pathology results, and surgical complications were compared between the two groups. The study findings indicate that in patients with BPH who underwent BiLEP, various parameters in the BPH + PI group including operation time, intraoperative flushing volume, hemoglobin drop value, postoperative white blood cells, postoperative C-reactive protein, and average pain score at 3 days postoperatively were significantly higher compared to those in the BPH group (p < 0.01). In addition, the IPSS and IIEF-5 scores of the BPH + PI group were significantly worse before surgery and at 2 weeks postoperatively compared to the BPH group (p < 0.01); however, no significant differences were observed between the two groups at 1 and 3 months postoperatively (p > 0.05). At 2 weeks postoperatively, the BPH + PI group exhibited significantly worse outcomes in terms of QoL, PVR, and Qmax compared to the BPH group (p < 0.01). However, there were no statistically significant differences between the two groups at 1 and 3 months postoperatively (p > 0.05). The incidence rates of postoperative complications, such as fever, prostatic capsule perforation, urinary tract irritation, bladder spasm, acute epididymitis, urinary tract infection, and urethral stricture, were higher in the BPH + PI group compared to the BPH group (p < 0.05). Nevertheless, there was no significant difference in the overall complication rates between the two groups (p > 0.05). There were no statistically significant differences observed between the two groups in postoperative irrigation volume, extubation time, hospitalization time, proportion of secondary operations, proportion of bladder injury, and proportion of urinary incontinence (p > 0.05). However, the proportion of reported prostate cancer after surgery in the BPH + PI group was significantly higher than that in the BPH group (p < 0.05). Histopathological prostatic inflammation does not have a significant impact on the long-term efficacy of BiLEP surgery immediately after biopsy. However, it does prolong surgery time, increase surgery-related complications, and influence short-term surgical outcomes and patient treatment experience. Therefore, it may be advisable to administer a course of anti-inflammatory treatment before performing BiLEP in such patients. Nevertheless, further high-quality studies are necessary to validate this approach.

Myriocin enhances the clearance of M. tuberculosis by macrophages through the activation of PLIN2.

Myriocin is an inhibitor of de novo synthesis of sphingolipids and ceramides. In this research, we showed myriocin could significantly reduce Mtb burden and histopathological inflammation in mice. However, the underlying mechanism remains unclear. RNA-seq analysis revealed a significant increase in gene expression of PLIN2/CD36/CERT1 after myriocin treatment. The reduced bactericidal burden was only reversed after silencing the lipid droplets (LDs) surface protein PLIN2. This suggests that myriocin enhances the ability of macrophages to clear Mtb depending on the PLIN2 gene, which is part of the PPARγ pathway. Indeed, we observed a significant increase in the number of LDs following myriocin treatment.IMPORTANCEMycobacterium tuberculosis has the ability to reprogram host cell lipid metabolism and alter the antimicrobial functions of infected macrophages. The sphingolipids, such as ceramides, are the primary host lipids utilized by the bacteria, making the sphingomyelinase/ceramide system critical in Mtb infections. Surprisingly, the antimicrobial effect of myriocin was found to be independent of its role in reducing ceramides, but instead, it depends on the lipid droplets surface protein PLIN2. Our findings provide a novel mechanism for how myriocin enhances Mtb clearance in macrophages.

Modified Citrus Pectin (MCP) Confers a Renoprotective Effect on Early-Stage Nephropathy in Type-2 Diabetic Mice.

Diabetic nephropathy (DN) is a significant global health concern with a high morbidity rate. Accumulating evidence reveals that Galectin-3 (Gal-3), a β-galactoside-binding lectin, is a biomarker in kidney diseases. Our study aimed to assess the advantageous impacts of modified citrus pectin (MCP) as an alternative therapeutic strategy for the initial and ongoing progression of DN in mice with type 2 diabetes mellitus (T2DM). The animal model has been split into four groups: control group, T2DM group (mice received intraperitoneal injections of nicotinamide (NA) and streptozotocin (STZ), T2DM+MCP group (mice received 100 mg/kg/day MCP following T2DM induction), and MCP group (mice received 100 mg/kg/day). After 4 weeks, kidney weight, blood glucose level, serum kidney function tests, histopathological structure alterations, oxidative stress, inflammation, apoptosis, and fibrosis parameters were determined in renal tissues. Our findings demonstrated that MCP treatment reduced blood glucose levels, renal histological damage, and restored kidney weight and kidney function tests. Additionally, MCP reduced malondialdehyde level and restored glutathione level, and catalase activity. MCP demonstrated a notable reduction in inflammatory and apoptosis mediators TNF-α, iNOS, TGF-βRII and caspase-3. Overall, MCP could alleviate renal injury in an experimental model of DN by suppressing renal oxidative stress, inflammation, fibrosis, and apoptosis mediators.

Lycopene Protects against Atrazine-Induced Kidney STING-Dependent PANoptosis through Stabilizing mtDNA via Interaction with Sam50/PHB1.

Atrazine (ATR) is a widely used herbicide worldwide that can cause kidney damage in humans and animals by accumulation in water and soil. Lycopene (LYC), a carotenoid with numerous biological activities, plays an important role in kidney protection due to its potent antioxidant and anti-inflammatory effects. The current study sought to investigate the role of interactions between mtDNA and the cGAS-STING signaling pathway in LYC mitigating PANoptosis and inflammation in kidneys induced by ATR exposure. In our research, 350 mice were orally administered LYC (5 mg/kg BW/day) and ATR (50 or 200 mg/kg BW/day) for 21 days. Our results reveal that ATR exposure induces a decrease in mtDNA stability, resulting in the release of mtDNA into the cytoplasm through the mPTP pore and the BAX pore and the mobilization of the cGAS-STING pathway, thereby inducing renal PANoptosis and inflammation. LYC can inhibit the above changes caused by ATR. In conclusion, LYC inhibited ATR exposure-induced histopathological changes, renal PANoptosis, and inflammation by inhibiting the cGAS-STING pathway. Our results demonstrate the positive role of LYC in ATR-induced renal injury and provide a new therapeutic target for treating renal diseases in the clinic.