Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions.

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

[Application of the theory of equal emphasis on muscle and bone in percutaneous vertebroplasty of lumbar osteoporotic compression fracture].

OBJECTIVE: To explore the clinical efficacy of percutaneous vertebroplasty(PVP) combined with nerve block in the treatment of lumbar osteoporotic vertebral compression fractures under the guidance of traditional chinese medicine "theory of equal emphasis on muscle and bone". METHODS: Total of 115 patients with lumbar osteoporotic vertebral compression fractures were treated by percutaneous vertebroplasty from January 2015 to March 2022, including 51 males and 64 females, aged 25 to 86 (60.5±15.9) years. Among them, 48 cases were treated with PVP operation combined with erector spinae block and joint block of the injured vertebral articular eminence (intervention group), and 67 cases were treated with conventional PVP operation (control group). The visual analogue scale(VAS) and Oswestry disability index(ODI) before operation, 3 days, 1 month and 6 months after operation between two groups were evaluated. The operation time, number of punctures and intraoperative bleeding between two groups were compared. RESULTS: The VAS and ODI scores of both groups improved significantly after operation compared with those before operation(P<0.05). Moreover, the VAS and ODI scores of 3 days and 1 month after operation of the intervention group improved more significantly than that of the control group(P<0.05). The difference of VAS and ODI scores before operation and 6 months after operation between two groups had no statistical significances(P>0.05). There was no statistically significant difference in the number of punctures and intraoperative bleeding between the two groups (P>0.05). CONCLUSION: Based on the theory of "equal emphasis on muscles and bones", PVP combined with nerve block can effectively relieve paravertebral soft tissue spasm and other "muscle injuries", which can significantly improve short-term postoperative low back pain and lumbar spine mobility compared to conventional PVP treatment, and accelerate postoperative recovery, resulting in satisfactory clinical outcomes.

Growth of Scenedesmus obliquus on anaerobic soybean wastewater using different wasted organics for high biomass production and nutrients recycling.

The microalgae culture in mixing sewage with different characteristics may significantly improve biomass production and nutrients recycling efficiency. In this study, three waste organic wastewater including molasses, alcohol and glycerol wastewater were mixed with anaerobic soybean wastewater as mediums for microalgae culture. The optimal mixture of molasses, alcohol and glycerol wastewater was at an initial carbon-nitrogen ratio of 7:1, 5:1 and 10:1, improving biomass production by 60.4%, 31.3% and 68.7%, respectively. The removal efficiencies of organics, ammonia nitrogen and phosphorus at optimal mixture were 54.8-62.4%, 79.5-99.1% and 49.3-61.5%, and the removal rates increased by 340-630%, 27.5-66.3% and 36.3-70.2% compared to the blank culture. In addition, the culture in mixed wastewater increased lipids contrast by 0.7-1.3 times, while achieving higher saturation in fatty acids. The results suggested that microalgae culture using mixed wastewater was a strategy for high biomass production and nutrients recycling efficiency.

Jujuboside B inhibits febrile seizure by modulating AMPA receptor activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Febrile seizure is a common neurologic disorder with limited treatment occurring in infants and children under the age of five. Jujuboside B (JuB) is a main bioactive saponin component isolated from the Chinese anti-insomnia herbal medicine Ziziphi Spinosae Semen (ZSS), seed of Ziziphus jujuba Mill, which has been proved to exhibit neuroprotective effects recently. AIM OF THE STUDY: In this study, we aimed at elucidating the effect of JuB on suppressing febrile seizure and the potential mechanisms. METHODS: Electroencephalogram (EEG) recording was used to monitor the severity of febrile seizures. The JuB in the brain was identified by mass spectrometry. Neuronal excitability was investigated using patch clamp. RESULTS: JuB (30 mg/kg) significantly prolonged seizure latency and reduced the severity in hyperthermia-induced seizures model mice. Hippocampal neuronal excitability was significantly decreased by JuB. And JuB significantly reduced the excitatory synaptic transmission mediated by α-amino-3-hydroxy-5-methyl-4-iso-xazolepropionic acid receptor (AMPAR), including evoked excitatory postsynaptic currents (eEPSCs), and miniature EPSCs (mEPSCs) in hippocampal neurons. Furthermore, JuB also significantly inhibited recombinant GluA1 and GluA2 mediated AMPA current in HEK293 cell and decreased the upregulation of [Ca2+]i induced by AMPA in primary cultured cortex neurons. CONCLUSIONS: JuB suppressed the excitability of hippocampal neurons by inhibiting the activity of AMPAR and reducing the intracellular free calcium, thereby relieving febrile seizures.

Discovery of Novel and Potent N-Methyl-d-aspartate Receptor Positive Allosteric Modulators with Antidepressant-like Activity in Rodent Models.

N-Methyl-d-aspartate receptors (NMDARs) are glutamate-gated Na+ and Ca2+-permeable ion channels involved in excitatory synaptic transmission and synaptic plasticity. NMDAR hypofunction has long been implicated in the pathophysiology including major depressive disorders (MDDs). Herein, we report a series of furan-2-carboxamide analogues as novel NMDAR-positive allosteric modulators (PAMs). Through structure-based virtual screen and electrophysiological tests, FS2921 was identified as a novel NMDAR PAM with potential antidepressant effects. Further structure-activity relationship studies led to the discovery of novel analogues with increased potentiation. Compound 32h caused a significant increase in NMDAR excitability in vitro and impressive activity in the forced swimming test. Moreover, compound 32h showed no significant inhibition of hERG or cell viability and possessed a favorable PK/PD profile. Our study presented a series of novel NMDAR PAMs and provided potential opportunities for discovering of new antidepressants.

Distribution characteristics and pollution risk evaluation of the nitrogen and phosphorus species in the sediments of Lake Erhai, Southwest China.

Erhai is a famous tectonic rift lake in China. In this study, the distribution of nitrogen and phosphorus species in Erhai sediment cores and their ecology risk were evaluated. The total nitrogen (TN) in the sediment cores ranged from 1583.3 to 8018.5 mg/kg. Nitrogen (N) was still accumulating in the sediment. For depths of 0 to 25 cm, the TN decreased dramatically and for deeper depths the TN got stabilized. The proportions of various N fractions in the sediments of the study areas ranked as follows: the strong oxidation extractable N (SOEF-N) > the weak acid extractable N (WAEF-N) > the strong alkali extractable N (SAEF-N) > the ion-exchangeable N (IEF-N). The total phosphorus (TP) ranged from 814.9 to 1442.3 mg/kg. The vertical distribution of each fraction of phosphorus showed that there were different sources of sediment phosphorus around the Erhai Lake. The results of nitrogen and phosphorus pollution evaluation in sediments by single pollution standard index method showed that the standard index of the TN (STN) ranged from 4.29 to 14.01, and the standard index of the TP (STP) ranged from 1.69 to 2.18. It illustrated that N and P in the sediments were the serious ecological pollution risks in Erhai Lake.

Distribution and sources of polycyclic aromatic hydrocarbons and phthalic acid esters in water and surface sediment from the Three Gorges Reservoir.

After the impoundment of the Three Gorges Reservoir (TGR), the hydrological situation of the reservoir has changed greatly. The concentration and distribution of typical persistent organic pollutants in water and sediment have also changed accordingly. In this study, the concentration, distribution and potential sources of 16 polycyclic aromatic hydrocarbons (PAHs) and 6 phthalic acid esters (PAEs) during the water drawdown and impoundment periods were investigated in water and sediment from the TGR. According to our results, PAHs and PAEs showed temporal and spatial variations. The mean ΣPAH and ΣPAE concentrations in water and sediment were both higher during the water impoundment period than during the water drawdown period. The water samples from the main stream showed larger ΣPAH concentration fluctuations than those from tributaries. Both the PAH and PAE concentrations meet the Chinese national water environmental quality standard (GB 3838-2002). PAH monomers with 2-3 rings and 4 rings were dominant in water, and 4-ring and 5-6-ring PAHs were dominant in sediment. Di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) were the dominant PAE pollutants in the TGR. DBP and DEHP had the highest concentrations in water and sediment, respectively. The main source of PAHs in water from the TGR was petroleum and emissions from coal and biomass combustion, whereas the main sources of PAHs in sediments included coal and biomass combustion, petroleum, and petroleum combustion. The main source of PAEs in water was domestic waste, and the plastics and heavy chemical industries were the main sources of PAEs in sediment.

Exogenous melatonin improves lead tolerance of bermudagrass through modulation of the antioxidant defense system.

Lead (Pb) is a major anthropogenic contaminant that can be devastating on both animals and plants. It is essential to develop methods to decrease the Pb contaminant in soil by phytoremediation using plants that are tolerance to Pb. In this study, we investigated the tolerance of bermudagrass (Cynodon dactylon (L.) Pers.) and the role of exogenous application of melatonin for improving its tolerance to Pb. Bermudagrass growing in soil treated with Pb at 1,000 or 2,000 mg kg-1 were assessed with or without melatonin pretreatment at various concentrations. Under Pb stresses, bermudagrass plants showed stunted growth and increased cellular oxidative stress. Pre-treating bermudagrass plants with melatonin at 20 or 100 µM significantly increased the activities of antioxidant enzymes (superoxide dismutase, catalase, peroxidase, ascorbate peroxidase, and glutathione reductase) and the contents of non-enzymatic antioxidants (ascorbic acid and glutathione), and decreased reactive oxygen species (hydrogen peroxide, superoxide), and ultimately reduced membrane lipid peroxidation and permeability. These changes contributed to improvements in the water status, photosynthetic pigment synthesis, and biomass production of bermudagrass under Pb stresses. Our study provides the first evidence that melatonin may be a promising tool for enhancing Pb tolerance and phytoremediation potential of bermudagrass.

Comparative analyses of physiological responses of Cynodon dactylon accessions from Southwest China to sulfur dioxide toxicity.

Sulfur dioxide (SO2), a major air pollutant in developing countries, is highly toxic to plants. To achieve better air quality and landscape, planting appropriate grass species in severe SO2 polluted areas is very critical. Cynodon dactylon, a widely used warm season turfgrass species, has good SO2-tolerant ability. In this study, we selected 9 out of 38 C. dactylon accessions from Southwest China as representatives of high, intermediate SO2-tolerant and SO2-sensitive accessions to comparatively analyze their physiological differences in leaves under SO2 untreated and treated conditions. Our results revealed that SO2-tolerant C. dactylon accessions showed higher soluble sugar, proline, and chlorophyll a contents under both SO2 treated and untreated conditions; higher chlorophyll b and carotenoid under SO2 treated condition; lower reactive oxygen species (ROS) level, oxidative damages, and superoxide dismutase (SOD) activities under SO2 treated condition; and higher peroxidase (POD) activities under SO2 untreated condition. Further results indicated that SO2-tolerant C. dactylon accessions had higher sulfur contents under both SO2 treated and untreated conditions, consistent with higher SO activities under both SO2 treated and untreated conditions, and higher SiR activities under SO2 treated condition. Taken together, our results indicated that SO2 tolerance of C. dactylon might be largely related to soluble sugar, proline and chlorophyll a contents, and SO enzyme activity.

Arsenic(V) Removal in Wetland Filters Treating Drinking Water with Different Substrates and Plants.

Constructed wetlands are an attractive choice for removing arsenic (As) within water resources used for drinking water production. The role of substrate and vegetation in As removal processes is still poorly understood. In this study, gravel, zeolite (microporous aluminosilicate mineral), ceramsite (lightweight expanded clay aggregate) and manganese sand were tested as prospective substrates while aquatic Juncus effuses (Soft Rush or Common Rush) and terrestrial Pteris vittata L. (Chinese Ladder Brake; known as As hyperaccumulator) were tested as potential wetland plants. Indoor batch adsorption experiments combined with outdoor column experiments were conducted to assess the As removal performances and process mechanisms. Batch adsorption results indicated that manganese sand had the maximum As(V) adsorption rate of 4.55 h-1 and an adsorption capacity of 42.37 µg/g compared to the other three aggregates. The adsorption process followed the pseudo-first-order kinetic model and Freundlich isotherm equations better than other kinetic and isotherm models. Film-diffusion was the rate-limiting step. Mean adsorption energy calculation results indicated that chemical forces, particle diffusion and physical processes dominated As adsorption to manganese sand, zeolite and gravel, respectively. During the whole running period, manganese sand-packed wetland filters were associated with constantly 90% higher As(V) reduction of approximate 500 µg/L influent loads regardless if planted or not. The presence of P. vittata contributed to no more than 13.5% of the total As removal. In contrast, J. effuses was associated with a 24% As removal efficiency.

Regulation effect of polysaccharides from Pleurotus tuber-regium (Fr.) on the immune activity of mice macrophages.

Pleurotus tuber-regium (Fr.) is widely consumed as a nutritious food due to its multiple health effects, especially immune function. This study was aimed at investigating its immune activity using the mice peritoneal macrophage model. Two polysaccharides, water and alkaline extraction of polysaccharides (W-PTR and A-PTR), from P. tuber-regium were used to test their immune functions and compare their possible activity differences. Results showed that both W-PTR and A-PTR showed a significant enhancement effect on the macrophage phagocytosis, and could activate the related enzymes, such as ATPases, lysozyme, and LDH, which are responsible for providing the maturation and proliferation process of macrophages with sufficient energy. In addition, levels of intracellular cytokines (IL-1, TNF-α, NO) were significantly increased after being treated with polysaccharides. A-PTR displayed a better performance than W-PTR in almost all tests. It is concluded that both polysaccharides could enhance the immune system by activating the macrophages and related enzymes, and induce the release of cytokines, indicating that polysaccharides are responsible for the immune function of Pleurotus tuber-regium (Fr.).

[Outcomes of patients with combined methylmalonic acidemia and homocystinuria after treatment].

OBJECTIVE: Combined methylmalonic acidemia with homocystinuria is a common form of methylmalonic acidemia in China. Patients with this disease can progress to death without timely and effective treatment. This study aimed to analyze the treatment outcomes of patients with combined methylmalonic acidemia and homocystinuria. METHOD: From September 2004 to April 2012, 58 patients with combined methylmalonic acidemia and homocystinuria (34 males and 24 females) were diagnosed and treated in our hospital. Fifty cases were from clinical patients including 42 early-onset cases and 8 late-onset cases. Their age when they were diagnosed ranged from 18 days to 30.8 years. The other 8 cases were from newborn screening. All the patients were treated with vitamin B12, betaine, folic acid, vitamin B6, and L-carnitine. The physical and neuropsychological development, general laboratory tests, the levels of amino acids, acylcarnitines, and homocysteine in blood, and organic acids in urine were followed up. RESULT: The follow-up period ranged from 1 month to 7.1 years. Three cases died (all were early-onset cases). In the other patients after treatment, the symptoms such as recurrent vomiting, seizures, lethargy, and poor feeding disappeared, muscle strength and muscle tension were improved, and general biochemical abnormalities such as anemia and metabolic acidosis were corrected. Among the surviving 55 cases, 49 had neurological impairments such as developmental delay and mental retardation. The median levels of blood propionylcarnitine and its ratio with acetylcarnitine, serum homocysteine, and urine methylmalonic acid were significantly decreased (P < 0.01), from 7.73 µmol/L (ranged from 1.5 to 18.61 µmol/L), 0.74 (ranged from 0.29 to 2.06), 97.3 µmol/L (ranged from 25.1 to 250 µmol/L) and 168.55 (ranged from 3.66 to 1032.82) before treatment to 2.74 µmol/L (ranged from 0.47 to 12.09 µmol/L), 0.16 (ranged from 0.03 to 0.62), 43.8 µmol/L (ranged from 17 to 97.8 µmol/L) and 6.81 (ranged from 0 to 95.43) after treatment, respectively. CONCLUSION: Patients with combined methylmalonic acidemia and homocystinuria respond to a combined treatment consisting of supplementation of hydroxycobalamin, betaine, folic acid, vitamin B6 and L-carnitine with clinical and biochemical improvement. But the long-term outcomes are unsatisfactory, with neurological sequelae in most patients.

Pharmacokinetics and excretion of hydroxysafflor yellow A, a potent neuroprotective agent from safflower, in rats and dogs.

Studies were conducted to characterize the pharmacokinetics and excretion of hydroxysafflor yellow A (HSYA) in rats and dogs after administration by intravenous injection or infusion. Plasma, urine, feces and bile concentrations of HSYA were measured using five validated mild HPLC methods. Linear pharmacokinetics of HSYA after the intravenous administrations were found at doses ranging from 3 to 24 mg/kg in rats and from 6 to 24 mg/kg in dogs. At a dose of 3 mg/kg, HSYA in urine, feces and bile was determined. For 48 h after dosing, the amount of urinary excretion accounted for 52.6 +/- 17.9 % (range: 31.1 - 78.7%, n = 6) of the dose, and the amount of fecal amount accounted for 8.4 +/- 5.3% (range 1.7 - 16.4%, n = 6) of the dose. Biliary excretion amount accounted for 1.4 +/- 1.0% (range 0.4-2.9%; n = 6) of the dose for 24 h after dosing. Percent plasma protein binding of HSYA ranged from 48.0 to 54.6% at 72 h. In summary, five mild HPLC methods for the determinations of HSYA in rat plasma, urine, feces, bile and dog plasma have been developed and successfully applied to preclinical pharmacokinetics and excretion of HSYA in rats and dogs. The results of excretion studies indicated that HSYA was rapidly excreted as unchanged drug in the urine. In view of previous pharmacological work, the concentration-dependent neuroprotective effect of HSYA in rats was defined.

[Preliminary attempt at the speciation of 25-elements in the Chinese medicinal herbs].

OBJECTIVE: To make an attempt at the multi-element speciation in the Chinese medicinal herbs by determining the concentrations of 25 elements in different extraction solutions. METHOD: Firstly, five Chinese medicinal herbs (Buddleja officinalis, Dictamnus dasycarpus, Myristica fragrans, Albizia judibrissin and Inula japonica) from the same region of China were treated to obtain water-soluble phase, lipid-soluble phase and non-soluble phase by water extraction, organic solvent extraction and acid digestion, respectively. Secondly, Phytolacca acinosa, a Chinese medicinal herb collected from 9 regions of China, was extracted by 0% EtOH, 50% EtOH, 75% EtOH, 95% EtOH, respectively, referring the Chinese Pharmacopoeia. Finally, the concentrations of 25 elements, such as Be, Cr, Cu, Zn, Ge, Sr, Y, Mo, Cd, Tl, Pb and REEs, in the above three phases were determined by ICP-MS. RESULT: Under the optimal conditions, all the 25 elements could be determined with detection limits ranged from 0.003 to 0.71 ng x g(-1). The average recoveries of the elements in P. acinosa were 88% approximately 119%, with the relative standard deviations 1.7% approximately 13.3%. It was observed that the determined 25 elements distributed in all the water-soluble, lipid-soluble and non-soluble phases, indicating that the inorganic species, organicspecies, as well as the protein bound species were coexisted in the herbs. Big differences of the element extraction rates could be found by using different ethanol solutions. CONCLUSION: With the aid of the obtained results, we may increase the extraction of necessary elements while decrease that of the toxic elements from the herbs by choosing a suitable solvent during the drug production.

[Determination of trace Cs, Th and U in ten kinds of human autopsy tissues by ICP-MS].

This paper studied the trace elements Cs, Th and U in ten kinds of human autopsy tissues by ICP-MS. The instrumental operating conditions were optimized for the measurement of Cs, Th and U. Rhodium (Rh) was used as an internal standard element to compensate matrix effect. Detection limits for Th, U and Cs were 5.7-17.8 pg x mL(-1). The recoveries for spiking liver samples were 96%-107%, and their RSDs were 4.8%-8.9%. Reference materials of NIST SRM 8414 Bovine and NIST SRM 1486 Bone Meal were analyzed by the described method, and the analytical results agreed well with the reference values. Human autopsy tissues samples were digested by mixed acid (HNO3 + HClO4). The determination of Cs, Th and U in lung, liver, bone, heart, stomach, spleen, muscle, kidney, thyroid gland and intestinum tenue was performed by ICP-MS without separation and enrichment procedures. The obtained results indicated that this method is rapid, sensitive and accurate; the distribution of the three elements is different from one to another human organ sample; the main organ targets for Th and U are lungs and kidneys; and a coordinated variation of Cs, Th and U concentration in lungs was found in the samples collected from Hebei and Sichuan provinces.

[Experimental study of puerarin injection on the hemorheology in acute blood-stasis model rats].

OBJECTIVE: To observe the effect of Puerarin Injection on the hemorheology in acute blood-stasis model rats. METHOD: The acute blood-stasis model rats were made by being soaked in ice water afer being injected adrenaline hydrochloride injection in a major dose. The changes of viscosity of whole blood and plasma, blood yield stress, erythrocyte aggregation and the maximum rate of platelet aggregation in the acute blood-stasis model rats were measured with Auto-Viscometer, and then the influence of Puerarin Injection on the hemorheology in the model rats was investigated. RESULT: The viscosity of whole blood and plasma, and blood yield stress in the acute blood-stasis model rats were significantly higher than those in the normal control group (P < 0.01, P < 0.05). Both the high dose and the low dose of Puerarin Injection could reduce the viscosity of whole blood and plasma, blood yield stress and the maximum rate of platelet aggregation in the acute blood-stasis model rats (P < 0.01, P < 0.05). The high dose could also reduce the erythrocyte aggregation and the deformed Index of red blood cell (P < 0.05). CONCLUSION: Puerarin Injection can ameliorate the hemorheology in acute blood-stasis model rats, and it has a dose-response relationship.