Multiple functions of HMGB1 in cancer.

High mobility group box 1 (HMGB1) is a nuclear DNA-binding protein with a dual role in cancer, acting as an oncogene and a tumor suppressor. This protein regulates nucleosomal structure, DNA damage repair, and genomic stability within the cell, while also playing a role in immune cell functions. This review comprehensively evaluates the biological and clinical significance of HMGB1 in cancer, including its involvement in cell death and survival, its potential as a therapeutic target and cancer biomarker, and as a prosurvival signal for the remaining cells after exposure to cytotoxic anticancer treatments. We highlight the need for a better understanding of the cellular markers and mechanisms involved in the involvement of HMGB1in cancer, and aim to provide a deeper understanding of its role in cancer progression.

Bioinformatics analysis and experimental verification of NLRX1 as a prognostic factor for esophageal squamous cell carcinoma.

Nucleotide binding and oligomeric domain-like receptor X1 (NLRX1), a member of the NLR family, is associated with the physiological and pathological processes of inflammation, autophagy, immunity, metabolism and mitochondrial regulation, and has been demonstrated to have pro- or antitumor effects in various tumor types. However, the biological function of NLRX1 in esophageal squamous cell carcinoma (ESCC) has remained elusive. In the present study, by using bioinformatics methods, the differential expression of NLRX1 at the mRNA level was examined. Overall survival, clinical correlation, receiver operating characteristic curve, Cox regression, co-expression, enrichment, immune infiltration and drug sensitivity analyses were carried out. A nomogram and a calibration curve were constructed. Changes in protein expression levels were investigated by immunohistochemistry and western blotting. The impact of NLRX1 on i) cell proliferation was evaluated by Cell Counting Kit-8 assays; ii) migration was examined by wound-healing assays; iii) migration and invasion were evaluated by Transwell assays; and iv) apoptosis was assessed by Annexin V/PI staining and flow cytometry. The results revealed that, compared to normal adjacent tissue, NLRX1 was lowly expressed in ESCC, and patients with low NLRX1 expression had a shorter survival time. NLRX1 was an independent prognostic factor for ESCC and was associated with tumor grading. Patients in the low-NLRX1 group showed a decrease in the infiltration of activated natural killer cells, monocytes and M0 macrophages, and these immune-cell infiltration levels were positively correlated with NLRX1 expression. Knocking down NLRX1 promoted the proliferation of KYSE450 cells, while overexpression of NLRX1 inhibited the proliferation of ECA109 cells. NLRX1 negatively regulated the PI3K/AKT signaling pathway in ESCC. These findings indicate that, through several mechanisms, NLRX1 suppresses tumor growth in ESCC, which offers new insight for investigating the causes and progression of ESCC, as well as for identifying more efficient therapeutic approaches.

The therapeutic effects of marine sulfated polysaccharides on diabetic nephropathy.

Marine sulfated polysaccharide (MSP) is a natural high molecular polysaccharide containing sulfate groups, which widely exists in various marine organisms. The sources determine structural variabilities of MSPs which have high security and wide biological activities, such as anticoagulation, antitumor, antivirus, immune regulation, regulation of glucose and lipid metabolism, antioxidant, etc. Due to the structural similarities between MSP and endogenous heparan sulfate, a majority of studies have shown that MSP can be used to treat diabetic nephropathy (DN) in vivo and in vitro. In this paper, we reviewed the anti-DN activities, the dominant mechanisms and structure-activity relationship of MSPs in order to provide the overall scene of MSPs as a modality of treating DN.

Impact of ovary-sparing treatment planning on plan quality, treatment time and gamma passing rates in intensity-modulated radiotherapy for stage I/II cervical cancer.

BACKGROUND: This study aimed to investigate the impact of ovary-sparing intensity-modulated radiotherapy (IMRT) on plan quality, treatment time, and gamma passing rates for stage I/II cervical cancer patients. METHODS: Fifteen stage I/II cervical cancer patients were retrospectively enrolled, and a pair of clinically suitable IMRT plans were designed for each patient, with (Group A) and without (Group B) ovary-sparing. Plan factors affecting plan quality, treatment time, and gamma passing rates, including the number of segments, monitor units, percentage of small-area segments (field area < 20 cm2), and percentage of small-MU segments (MU < 10), were compared and statistically analyzed. Key plan quality indicators, including ovarian dose, target dose coverage (D98%, D95%, D50%, D2%), conformity index, and homogeneity index, were evaluated and statistically assessed. Treatment time and gamma passing rates collected by IBA MatriXX were also compared. RESULTS: The median ovarian dose in Group A and Group B was 7.61 Gy (range 6.71-8.51 Gy) and 38.52 Gy (range 29.84-43.82 Gy), respectively. Except for monitor units, all other plan factors were significantly lower in Group A than in Group B (all P < .05). Correlation coefficients between plan factors, treatment time, and gamma passing rates that were statistically different were all negative. Both Groups of plans met the prescription requirement (D95% ≥ 45.00 Gy) for clinical treatment. D98% was smaller for Group A than for Group B (P < .05); D50% and D2% were larger for Group A than for Group B (P < .05, P < .05). Group A plans had worse conformity index and homogeneity index than Group B plans (P < .05, P < .05). Treatment time did not differ significantly (P > .05). Gamma passing rates in Group A were higher than in Group B with the criteria of 2%/3 mm (P < .05) and 3%/2 mm (P < .05). CONCLUSION: Despite the slightly decreased quality of the treatment plans, the ovary-sparing IMRT plans exhibited several advantages including lower ovarian dose and plan complexity, improved gamma passing rates, and a negligible impact on treatment time.

Metabolomics analysis of the effects of different litter size on reproductive metabolism and oxidative stress in breeding pigeon (Columba livia).

The pigeon breeding industry employs a high-rearing pattern to achieve economic benefits. However, too many squabs consume more energy of the breeding pigeons causing adverse effects on their breeding performance. To determine the optimal rearing patterns and the effects of different numbers of squabs on reproductive performance, oxidative stress, and glucolipid metabolism of lactating breeding pigeons in winter, three rearing patterns consisting of "2 + 2″, "2 + 3″ and "2 + 4" (a pair of breeding pigeons feeding two, three and four squabs, respectively) were adopted using European Mimas white pigeons breed. The feed intake, bodyweight loss, feed-to-meat ratio, and squab mortality were linearly increased with the number of squabs during lactation, while the bodyweight recovery rate and squab growth performance were significantly slowed down after lactation. Similarly, the laying rate was linearly decreased on days 16, 17, and 18 of lactation, with a similar pattern on the re-laying rate on days 11, 12, and 13 after first laying. In addition, the number of non-laying pigeons in the second batch was significantly increased, implying that the number of squabs significantly affected the reproductive performance of female pigeons. The eggshell weight and thickness in the "2 + 3″ group were significantly increased. However, the number of squabs in the "2 + 3″ group had no significant effect on plasma calcium (Ca) and phosphorus (P) levels. Analysis of the glucolipid metabolism index and oxidative stress level of pigeons further revealed that the contents of triglyceride (TG), total cholesterol (T-CHO), and low-density lipoprotein cholesterol (LDL-C) in the plasma of male pigeons were significantly decreased with the increase in the number of squabs, but there was no obvious oxidative stress. On the contrary, glucose (GLU), TG, malondialdehyde (MDA) in the plasma of female pigeons were significantly increased, total antioxidant capacity (T-AOC) were significantly decreased, implying that the female pigeons suffered more oxidative stress and more dramatic changes in glucolipid metabolism. Metabolomics revealed that the differential metabolites in the plasma of female pigeons in "2 + 2″, "2 + 3″, and "2 + 4″ groups were significantly enriched in the fatty acid, phospholipid, sphingolipid metabolism, and the Krebs cycle pathways, especially under "2 + 4″ rearing pattern. Overall, in female pigeons, the available lipids were reduced; hence, their body turned to sugar dysplasia and protein utilization mode, increasing the oxidative stress level and decreasing their reproductive performance. Therefore, an increased number of squabs significantly affects the body condition and reproductive performance of breeding pigeons. The "2 + 3″ rearing pattern is the most suitable for winter breeding pigeon production under the current nutrition level.

Glucose-Responsive Nanochaperones Mediate Exendin-4 Delivery for Enhancing Therapeutic Effects.

Exendin-4 (Ex-4) is a promising therapeutic peptide for the clinical treatment of type 2 diabetes, but its instability and immunogenicity result in a short circulating half-life and low bioavailability, which severely limit its clinical application. Here, complex micelles with 4-carboxy-3-fluorophenylboronic acid (FPBA)-modified and positively charged hydrophobic domains on the surface were devised as nanochaperones to mediate the delivery of Ex-4. The nanochaperones can bind Ex-4 on the surface via the synergy of electrostatic and hydrophobic interactions, leading to efficient loading and stabilization of Ex-4. More importantly, the immunogenic site of Ex-4 was shielded by the nanochaperones, thereby effectively reducing the immune clearance and prolonging the half-life. Hyperglycemia-triggered release of Ex-4 was achieved by the hydrophobic to the hydrophilic transformation of the FPBA-modified domains and the introduced negative charge because of the binding of glucose by FPBA. The Ex-4-loaded nanochaperones exhibited an enhanced therapeutic effect on type 2 diabetic mice.

In Situ Antigen-Capturing Nanochaperone Toward Personalized Nanovaccine for Cancer Immunotherapy.

Personalized cancer vaccination using nanomaterials holds great potential for cancer immunotherapy. Here, a nanochaperone (PBA-nChap) is tailored for in situ capture of tumor-associated antigens (TAAs) to improve cancer immunotherapy. The PBA-nChap is capable of i) efficiently capturing TAAs in situ; ii) protecting TAAs from degradation; iii) transporting TAAs to antigen-presenting cells and promoting cross-presentation. Intratumor injection of PBA-nChap in combination with pretreatment with photodynamic therapy (PDT) significantly enhances immune response and exhibits excellent antitumor efficacy. Moreover, nanovaccine prepared by simply co-culturing PBA-nChap with tumor cell fragments from surgery resected primary tumor in vitro synergized with immune checkpoint blockade (ICB) therapy can effectively inhibit tumor recurrence and metastasis after an operation. This work provides a promising platform for personalized cancer vaccination.

Near-Infrared-to-Near-Infrared Optical Thermometer BaY2O4: Yb3+/Nd3+ Assembled with Photothermal Conversion Performance.

Nowadays, the construction of photothermal therapy (PTT) agents integrated with real-time thermometry for cancer treatment in deep tissues has become a research hotspot. Herein, an excellent photothermal conversion material, BaY2O4: Yb3+/Nd3+, assembled with real-time optical thermometry is developed successfully. Ultrasensitive temperature sensing is implemented through the fluorescence intensity ratio of thermally coupled Nd3+: 4Fj (j = 7/2, 5/2, and 3/2) with a maximal absolute and relative sensitivity of 68.88 and 3.29% K-1, respectively, which surpass the overwhelming majority of the same type of thermometers. Especially, a thermally enhanced Nd3+ luminescence with a factor of 180 is detected with irradiation at 980 nm, resulting from the improvement in phonon-assisted energy transfer efficiency. Meanwhile, the photothermal conversion performance of the sample is excellent enough to destroy the pathological tissues, of which the temperature can be raised to 319.3 K after 180 s of near-infrared (NIR) irradiation with an invariable power density of 13.74 mW/mm2. Besides, the NIR emission of Nd3+ can reach a depth of 7 mm in the biological tissues, as determined by an ex vivo experiment. All the results show the potential application of BaY2O4: Yb3+/Nd3+ as a deep-tissue PTT agent simultaneously equipped with photothermal conversion and temperature sensing function.

The effect of Liuwei Dihuang decoction on PI3K/Akt signaling pathway in liver of type 2 diabetes mellitus (T2DM) rats with insulin resistance.

ETHNOPHARMACOLOGICAL RELEVANCE: Liuwei Dihaung decoction (LWDHT) is a well-known classic traditional Chinese medicine formula, consists of six herbs including Rehmannia glutinosa Libosch.(family: Scrophulariaceae), Cornus officinalis Sieb.(family: Cornaceae), Dioscorea opposite Thunb.(family: Dioscoreaceae), Alisma orientale(G. Samuelsson) Juz (family: Alismataceae), Poria cocos (Schw.) Wolf (family: Polyporaceae) and Paeonia suffruticosa Andrews (family: Paeoniaceae). It has been used in the treatment of many types of diseases with signs of deficiency of Yin in the kidneys in China clinically. This study is aimed at investigating the effect of Liuwei dihuang decoction on PI3K/Akt signaling pathway in liver of T2DM rats with insulin resistance. MATERIALS AND METHODS: T2DM model was induced in male Sprague-Dawley (SD) rats by high sugar and high fat diets combined with small dose of streptozocin (STZ) injection. The successful T2DM rats were randomly allocated three group--vehicle group, positive control group and Liuwei Dihuang decoction group. After 12-weeks treatment with distilled water, rosiglitazone and LWDHT by intragastric administration respectively, the rats were put to death in batches. The variance of fasting blood glucose (FBG) and fasting insulin (FINS) in serum were determined, the pathological changes of each rats' liver were observed by hematoxylin-eosin (HE) staining, the expression of insulin receptor substrate 2(IRS2), phosphatidylinositol 3-kinase (PI3K) and protein kinas B (Akt) involving the canonical PI3K/Akt signaling pathway were detected by Real-time fluorescent quantitative PCR (RT-PCR), and the expression level of IRS2, PI3K, Akt protein and phosphorylated IRS2, PI3K, Akt protein were evaluated by Western Blot. All the data were analyzed by SPSS 17.0. RESULTS: Four weeks of treatment with LWDHT could significantly decrease the level of FBG and FINS in serum, improve the cellular morphology of liver, kidney, pancreas tissue, and the expression of IRS2, PI3K, Akt mRNA and phosphorylated IRS2, PI3K, Akt protein involved in the canonical PI3K/Akt signaling pathway of T2DM rats in liver were significantly up-regulated, while the total IRS2, PI3K, and Akt protein had no obvious changes. CONCLUSIONS: The results suggest that Liuwei Dihuang decoction could intervene insulin resistance of T2DM, in part, through regulation of canonical PI3K/Akt signaling pathway of T2DM rats in liver.