Far-infrared radiation and its therapeutic parameters: A superior alternative for future regenerative medicine?

In future regenerative medicine, far-infrared radiation (FIR) may be an essential component of optical therapy. Many studies have confirmed or validated the efficacy and safety of FIR in various diseases, benefiting from new insights into FIR mechanisms and the excellent performance of many applications. However, the lack of consensus on the biological effects and therapeutic parameters of FIR limits its practical applications in the clinic. In this review, the definition, characteristics, and underlying principles of the FIR are systematically illustrated. We outline the therapeutic parameters of FIR, including the wavelength range, power density, irradiation time, and distance. In addition, the biological effects, potential molecular mechanisms, and preclinical and clinical applications of FIR are discussed. Furthermore, the future development and applications of FIR are described in this review. By applying optimal therapeutic parameters, FIR can influence various cells, animal models, and patients, eliciting diverse underlying mechanisms and offering therapeutic potential for many diseases. FIR could represent a superior alternative with broad prospects for application in future regenerative medicine.

Multi-stress resilience in plants recovering from submergence.

Submergence limits plants' access to oxygen and light, causing massive changes in metabolism; after submergence, plants experience additional stresses, including reoxygenation, dehydration, photoinhibition and accelerated senescence. Plant responses to waterlogging and partial or complete submergence have been well studied, but our understanding of plant responses during post-submergence recovery remains limited. During post-submergence recovery, whether a plant can repair the damage caused by submergence and reoxygenation and re-activate key processes to continue to grow, determines whether the plant survives. Here, we summarize the challenges plants face when recovering from submergence, primarily focusing on studies of Arabidopsis thaliana and rice (Oryza sativa). We also highlight recent progress in elucidating the interplay among various regulatory pathways, compare post-hypoxia reoxygenation between plants and animals and provide new perspectives for future studies.

Intrathecal Injection of Botulinum Toxin Type A has an Analgesic Effect in Male Rats CCI Model by Inhibiting the Activation of Spinal P2X4R.

Purinergic receptor P2X4 (P2X4R) plays an essential role in neuropathic pain. However, the specific mechanism needs to be clarified. Botulinum toxin type A is a neurotoxin produced by Clostridium botulinum type A. This study found that intrathecal injection of botulinum toxin type A produced an excellent analgesic effect in a rat model of chronic constriction sciatic nerve injury and inhibited the activation of P2X4R, microglia, and astrocytes. The administration of a P2X4R activator can up-regulate the expression of P2X4R and eliminate the analgesic effect of intrathecal injection of botulinum toxin type A. In addition, we found that microglia and astrocytes in the spinal cord of rats injected with botulinum toxin type A were reactivated after administration of the P2X4R activator. Our results suggest that intrathecal injection of botulinum toxin type A has an analgesic effect in a rat model of chronic constriction sciatic nerve injury by inhibiting the activation of P2X4R in the spinal cord.

Impaired vessel relaxation response and increased infarct size in smooth muscle cannabinoid receptor 1 knockout mice.

Cannabinoids are reported to regulate cardiovascular functions. Cannabinoid receptors 1 (CB1Rs) are widely expressed in both the neuronal system and vascular system, but the contribution of CB1Rs in vascular smooth muscle (CB1RSM) to cardiovascular functions is not clear yet. In this research, we analyzed the effects of CB1RSM on blood pressure, vasoconstriction, and vasodilation abilities by using conditionally CB1R knockout mice (CB1RSMKO). The results show no significant difference in basal blood pressure between the conscious CB1RSMKO and control mice, indicating that CB1RSM is not essential for basal blood pressure maintenance. The constriction of the CB1RSMKO mesenteric artery in vitro was not significantly altered compared with that of the control mice. In contrast, the relaxation to CB1R agonist 2-AG or WIN55212-2 was decreased in CB1RSMKO vessels, suggesting that activation of CB1RSM mediates the vasodilation effect of cannabinoids. Ischemia stroke mouse model was used to further identify the potential function of CB1RSM in pathological conditions, and the results showed that the infarct volume in CB1RSMKO mice is significantly increased compared with the control littermates. These results suggest that vascular CB1R may not play a central role in basal vascular health maintenance but is protective in ischemia states, such as stroke. The protection function may be mediated, at least partly, by the relaxation effect of CB1RSM-dependent activities of endocannabinoids.

[Biomarkers related to cognitive dysfunction in APP/PS1 mice based on non-targeted metabonomics and intervention mechanism of Huanglian Jiedu Decoction].

Through the non-targeted metabonomics study on endogenous substances in APP/PS1 transgenic mice, this paper aimed to discover biomarkers related to APP/PS1 mice with cognitive dysfunction, and find targets of Huanglian Jiedu Decoction(HLJDD) in the treatment of Alzheimer's disease(AD) and its mechanism. The brain tissue and serum metabolic mass spectrometry of mice were analyzed by ultra-high performance liquid chromatography-Orbitrap mass spectrometry(UPLC-Orbitrap MS). Through partial least squares-discriminant analysis(PLS-DA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), the metabolic data of the normal group, the model group, the high-dose and low-dose HLJDD groups, and the berberine group were compared and analyzed to screen out potential biomarkers, and the relevant metabolic pathways were constructed with the help of the Kyoto Encyclopedia of Genes and Genomes(KEGG) database. Forty-five potential endogenous metabolites were identified, including 13 in brain and 35 in serum, among which leukotriene B4, tyrosine, and adenosine were expected to be differential metabolites related to cognitive function. HLJDD recalled 22 differential metabolites, and the pathways mainly involved in aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, pantothenic acid and coenzyme A biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, and arachidonic acid metabolism. These pathways suggested that the main mechanism of HLJDD in the intervention of AD was to inhibit central and peripheral inflammation, and regulate energy metabolism, fatty acid metabolism, and amino acid metabolism. HLJDD has a certain effect on the improvement of cognitive dysfunction, and regulates relative pathways by recalling endogenous differential metabolites, which helps to further discover the biomarkers of AD and clarify the intervention mechanism of HLJDD in the treatment of AD.

pik3r3b, a novel immune-related gene in Nile tilapia (Oreochromis niloticus): Identification, expression and analysis of antibacterial activity.

A full-length cDNA encoding phosphatidylinositol 3-kinase regulatory subunit gamma b gene in Nile tilapia (Oreochromis niloticus), termed as On-pik3r3b, was identified and characterized in this study. The sequence analysis demonstrated that the full-length cDNA of On-pik3r3b was 2018 bp, containing a 5' untranslated region (UTR) of 171 bp, an open reading frame (ORF) of 1422 bp and a 3' UTR of 425 bp. Its protein sequence displayed a high degree of identity with other fish. Using qPCR, the expression patterns of On-pik3r3b were investigated. In healthy Nile tilapia, the transcripts of On-pik3r3b were detected in all examined tissues, except the skin. Upon the stimulation with Streptococcus agalactiae, the On-pik3r3b expression level in liver, spleen, kidney and gill were significantly increased at 12 h after infection. The recombinant On-pik3r3b showed in vitro antibacterial activity, against S. agalactiae and E. coli. Our observation strongly indicates that On-pik3r3b is involved in the innate immune response in Nile tilapia.

Efficient assembly of oligomannosides using the hydrophobically assisted switching phase method.

The hydrophobically assisted switching phase (HASP) method was applied in the assembly of oligomannosides. A new mannosyl donor with high reactivity was selected after a series of optimization studies, which was suitable for the synthesis of oligomannosides via the HASP method. The practicability of the HASP method towards the synthesis of branched oligosaccharides was explored and two branched penta-mannosides were assembled efficiently.

The edaravone and 3-n-butylphthalide ring-opening derivative 10b effectively attenuates cerebral ischemia injury in rats.

AIM: Compound 10b is a hybrid molecule of edaravone and a ring-opening derivative of 3-n-butylphthalide (NBP). The aim of this study was to examine the effects of compound 10b on brain damage in rats after focal cerebral ischemia. METHODS: SD rats were subjected to 2-h-middle cerebral artery occlusion (MCAO). At the onset of reperfusion, the rats were orally treated with NBP (60 mg/kg), edaravone (3 mg/kg), NBP (60 mg/kg)+edaravone (3 mg/kg), or compound 10b (70, 140 mg/kg). The infarct volume, motor behavior deficits, brain water content, histopathological alterations, and activity of GSH, SOD, and MDA were analyzed 24 h after reperfusion. The levels of relevant proteins in the ipsilateral striatum were examined using immunoblotting. RESULTS: Administration of compound 10b (70 or 140 mg/kg) significantly reduced the infarct volume and neurological deficits in MCAO rats. The neuroprotective effects of compound 10b were more pronounced compared to NBP, edaravone or NBP+edaravone. Furthermore, compound 10b significantly upregulated the protein levels of the cytoprotective molecules Bcl-2, HO-1, Nrf2, Trx, P-NF-κB p65, and IκB-α, while decreasing the expression of Bax, caspase 3, caspase 9, Txnip, NF-κB p65, and P-IκB-α. CONCLUSION: Oral administration of compound 10b effectively attenuates rat cerebral ischemia injury.

An HPLC method for the quantitation of 3-pentylbenzo[c]thiophen-1(3H)-one in dog plasma and its application to a pharmacokinetic study.

A simple, sensitive and reproducible high-performance liquid chromatography (HPLC) assay method was developed for the estimation of 3-pentylbenzo[c]thiophen-1(3H)-one (S5 ), a potential anti-ischemic stroke agent, in dog plasma. The analytical procedure involves protein precipitation of S5 and nobiletin (internal standard) from dog plasma with acetonitrile. Chromatographic separation was achieved on Sapphire C18 analytical column with methanol-water (80:20, v/v) as mobile phase. The eluate was monitored using a UV detector set at 260 nm. The calibration curves were linear over the range of 0.2-20 µg/mL. Absolute recoveries of S5 were 79.2-86.1% from dog plasma. The intra- and inter-day relative standard deviation precisions were <7 and 5%, respectively. The method was successfully applied to the pharmacokinetic study of S5 in beagle dogs.

[Retrospective analysis of 50 cases of senile syphilis].

OBJECTIVE: To summarize the epidemiological features of senile syphilis. METHOD: The clinical data of 50 elderly (>60 years) patients with syphilis who were treated in the Clinic of Sexually Transmitted Diseases of Peking Union Medical College Hospital were retrospectively analyzed. RESULTS: There were 31 men and 19 women (male to female ratio:1.6:1). Non-marital sexual intercourse was the main route of transmission. The disease was mainly found before surgeries. Among these 50 syphilis cases, 3 were primary syphilis, 13 were secondary syphilis, 10 were early latent syphilis, 12 were late latent syphilis, and 12 were latent syphilis of unknown duration. Co-morbidities with other sexually transmitted diseases were found in 4 patients. The rate of sero-resistance was 40%. CONCLUSIONS: The incidence of syphilis in the senile population is higher than we expected. Routine serological screening for syphilis is required in clinical settings. The underlying diseases, human hosts-related spirochetes, and laboratory testing techniques are important reasons for the false positive findings in senile patients.

Botulinum toxin type A inhibits M1 macrophage polarization by deactivation of JAK2/STAT1 and IκB/NFκB pathway and contributes to scar alleviation in aseptic skin wound healing.

The non-neuronal and non-muscular effects of botulinum toxin type A (BTXA) on scar reduction has been discovered. This study was designed to investigate the effects of BTXA on macrophages polarization during the early stage of skin repair. A skin defect model was established on the dorsal skin of SD rats. BTXA was intracutaneous injected into the edge of wound immediately as the model was established. Histological examinations were performed on scar samples. Raw 264.7 was selected as the cell model of recruited circulating macrophages, and was induced for M1 polarization by LPS. Identify the signaling pathways that primarily regulated M1 polarization and respond to BTXA treatment. Application of BTXA at early stage of injury significantly reduced the scar diameter without delaying wound closure. BTXA treatment improved fiber proliferation and arrangement, and inhibited angiogenesis in scar granular tissue. The number of M1 macrophages and the levels of pro-inflammation were decreased after treated with BTXA in scar tissues. LPS activated JAK2/STAT1 and IκB/NFκB pathways were downregulated by BTXA, as well as LPS induced M1 polarization. At early stage of skin wound healing, injection of BTXA effectively reduced the number of M1 macrophages and the levels of pro-inflammatory mediators which contributes to scar alleviation. BTXA resisted the M1 polarization of macrophages induced by LPS via deactivating the JAK2/STAT1 and IκB/NFκB pathways.

Evaluation of therapeutic benefits of botulinum toxin for foot dystonia associated with Parkinson's disease.

BACKGROUND: Foot dystonia occurs in patients with Parkinson's disease (PD) and leads to pain, malformation, and difficulty with walking. Botulinum toxin injections may be effective for foot dystonia, but the extent of improvement and effects on motor function are unclear. METHODS: In this study, we performed botulinum toxin injections for foot dystonia in 25 patients with PD. At 3 weeks and 3 months post-infection, we assessed changes in plantar pressure distribution utilizing the Pressure Plate system; dystonia using the Modified Ashworth Spasm score; pain using the visual analog scale (VAS) score; and lower extremity function using the Calf-raise Senior (CRS) test, Timed Up and Go (TUG) test, and gait parameters (eg, stride length, step length). RESULTS: We found improved Modified Ashworth Spasm score (p < 0.01) and VAS score (p < 0.01) post-injection. CRS test score (3 weeks, p = 0.006; 3 months, p = 0.068), stride length (3 weeks, p = 0.012; 3 months, p = 0.715), and step length (3 weeks, p = 0.011; 3 months, p = 0.803) also improved. Plantar pressure distribution improved after botulinum toxin injection (metatarsal 1, 3 weeks, p = 0.031; 3 months, p = 0.144; metatarsal 2, 3 weeks, p = 0.049; 3 months, p = 0.065; metatarsal 3, 3 weeks, p = 0.002; 3 months, p = 0.017; metatarsal 4, 3 weeks, p = 0.017; 3 months, p = 0.144; medial heel, 3 weeks, p = 0.01; 3 months, p = 0.395; lateral heel, 3 weeks, p = 0.035; 3 months, p = 0.109). CONCLUSION: Botulinum toxin injection for foot dystonia in patients with PD can reduce spasms and pain and normalize plantar pressure distribution, which improves balance and lower extremity function.

Calcium-dependent activation of CPK12 facilitates its cytoplasm-to-nucleus translocation to potentiate plant hypoxia sensing by phosphorylating ERF-VII transcription factors.

Calcium-dependent protein kinases (CDPKs/CPKs) are key regulators of plant stress signaling that translate calcium signals into cellular responses by phosphorylating diverse substrate proteins. However, the molecular mechanism by which plant cells relay calcium signals in response to hypoxia remains elusive. Here, we show that one member of the CDPK family in Arabidopsis thaliana, CPK12, is rapidly activated during hypoxia through calcium-dependent phosphorylation of its Ser-186 residue. Phosphorylated CPK12 shuttles from the cytoplasm to the nucleus, where it interacts with and phosphorylates the group VII ethylene-responsive transcription factors (ERF-VII) that are core regulators of plant hypoxia sensing, to enhance their stabilities. Consistently, CPK12 knockdown lines show attenuated tolerance of hypoxia, whereas transgenic plants overexpressing CPK12 display improved hypoxia tolerance. Nonethelss, loss of function of five ERF-VII proteins in an erf-vii pentuple mutant could partially suppress the enhanced hypoxia-tolerance phenotype of CPK12-overexpressing lines. Moreover, we also discovered that phosphatidic acid and 14-3-3κ protein serve as positive and negative modulators of the CPK12 cytoplasm-to-nucleus translocation, respectively. Taken together, these findings uncover a CPK12-ERF-VII regulatory module that is key to transducing calcium signals from the cytoplasm into the nucleus to potentiate hypoxia sensing in plants.

Age-related self-DNA accumulation may accelerate arthritis in rats and in human rheumatoid arthritis.

The incidence of rheumatoid arthritis (RA) is increasing with age. DNA fragments is known to accumulate in certain autoimmune diseases, but the mechanistic relationship among ageing, DNA fragments and RA pathogenesis remain unexplored. Here we show that the accumulation of DNA fragments, increasing with age and regulated by the exonuclease TREX1, promotes abnormal activation of the immune system in an adjuvant-induced arthritis (AIA) rat model. Local overexpression of TREX1 suppresses synovial inflammation in rats, while conditional genomic deletion of TREX1 in AIA rats result in higher levels of circulating free (cf) DNA and hence abnormal immune activation, leading to more severe symptoms. The dysregulation of the heterodimeric transcription factor AP-1, formed by c-Jun and c-Fos, appear to regulate both TREX1 expression and SASP induction. Thus, our results confirm that DNA fragments are inflammatory mediators, and TREX1, downstream of AP-1, may serve as regulator of cellular immunity in health and in RA.

[Clinical features and serologic analysis of latent syphilis].

OBJECTIVE: To summarize the clinical features and analyze the serologic test results of latent syphilis. METHODS: The clinical data of 601 patients with latent syphilis who were treated in the sexually transmitted disease centre of Peking Union Medical College Hospital between January 2001 and November 2007 were retrospectively analyzed. RESULTS: Of the 601 cases of latent syphilis, there were 174 cases of early latent syphilis(EL), 170 cases of late latent syphilis(LL), and 257 cases of unknown latent syphilis. Male to female ratio was 0.74:1256 males and 345 females, respectively). Patients aged 20-39 years accounted for the largest proportion. Non-marital sexual intercourse was the main route of infection. Forty-six patients (7.65%) were co-infected with other sexually transmitted diseases. A total of 251 cases of latent syphilis (41.76%) were confirmed when the patients were receiving tests for other sexually transmitted diseases or suspected sexually transmitted diseases. Of the 601 patients with EL, LL and unknown latency, the proportion of serum rapid plasma reagin(RPR) titers higher than or equal to 8 were 72.99% (127/174), 52.94% (90/170), and 60.31%(155/257), respectively. Compared with the early syphilis, serological negative conversion rate was significantly lower after treatment for l2 months in the early latent syphilis patients (P=0.044). CONCLUSION: Education and awareness raising on syphilis should be strengthened to lower the prevalence of latent syphilis.

[Analysis of 1125 syphilis cases].

OBJECTIVE: To summarize the epidemiological, clinical and serological features of syphilis. METHOD: The clinical data of 1125 patients with syphilis were retrospectively analyzed. RESULTS: Non-marital sexual intercourse is the main route of infection. The 129 cases of primary syphilis were featured by extragenital chancres and the 357 cases of secondary syphilis were featured by scaling macules on the palms and soles and condylomata lata. Early latent syphilis were detected in 178 cases, late latent syphilis in 174 cases, and latent syphilis of unknown duration in 285 cases. Concurrent infection with other sexually transmitted diseases were noted in 107 cases (9.51%). Most patients were treated with benzathine penicillin, and only 31 patients (2.75%) were allergic to this therapy. Except for the primary syphilis, the sensitivity of syphilis serological tests (including rapid plasma regain test, treponema pallidum particle agglutination, treponema pallidum hemagglutination assay, and fluorescent treponemal antibody-absorption) were higher than 97%. CONCLUSIONS: The incidence of latent syphilis is high, while the incidence of late syphilis is low. Penicillin remains the treatment of choice for syphilis.

[Clinical analysis and study of immunological function in syphilis patients with seroresistance].

OBJECTIVE: To investigate the relevant factors of seroresistance of syphilis by clinical analysis and study of immunological function. METHODS: The clinical data of 172 patients with syphilis were analyzed to observe the correlation of seroresistance with the factors including original titer of rapid plasma regain (RPR), disease course, and medication. Flow cytometry was used to analyze the proportions of T-lymphocyte subset and NK cells in the peripheral blood of 40 untreated syphilitic patients at various stages, 20 syphilitic patients whose serology turned negative after treatment, 20 serum resistance patients, and 18 healthy controls. RESULTS: The seroresistance rate was 8.7% in the primary syphilis patients (2/23), significantly lower than that of the latent syphilis patients (42.2%, 38/90, P = 0.001). The seroresistance rate of the patients treated with benzathine penicillin was 26.4% (42/159), significantly lower that of the patients treated with macrolides (76.9%, 10/13, P = 0.000). The proportion of CD8(+) T cells of the untreated syphilitic patients was (30% +/- 8%), significantly higher than that of the normal controls [(24% +/- 4%), P < 0.01]. The proportion of NK cells of the untreated syphilitic patients was (13% +/- 5%), significantly lower than that of the normal controls (16% +/- 6%, P < 0.05). The proportion of CD3(+) T cells of the patients whose serology turned negative after treatment was (71% +/- 7%), significantly higher than that of the normal controls (65% +/- 7%, P < 0.05). The proportion of CD8(+) T cells of the patients whose serology turned negative after treatment was (29% +/- 7%), significantly higher than that of the normal controls (24% +/- 4%, P < 0.01). There were not significant differences in the proportions of different cells among the patients with seroresistance, serological negative conversion, and normal controls. CONCLUSION: Syphilis patients with a high baseline RPR titer, a latent course and macrolide therapy are prone to be seroresistant. Whether the occurrence of serum resistance is related to the inhibition of cell-mediated immunity requires further exploration.

Combined enzymatic hydrolysis and selective fermentation for green production of alginate oligosaccharides from Laminaria japonica.

Alginate oligosaccharides (AOS) showed various biological activities. Traditional protocol for producing AOS was a multiple-step and high-pollution procedure. In this study, a rapid and efficient AOS producing method was developed directly from Laminaria japonica. Natural sun-dried L. japonica with a feed ratio of 1:7 (w/v) was pretreated using cellulase with a dry weight of 3%, for releasing the fermentable sugars (8.5 g/L glucose and 15.2 g/L mannitol). Then, the engineered yeast Yarrowia lipolytica strain with alginate lyase activity was grown using an algae-based medium. After fermentation for 72 h, glucose and mannitol were completely consumed, and 71.8 mM AOS was extracted from the fermentation supernatant. The degree of polymerization (DP) was ranging from 2 to 3. The recovery yield of AOS was about 91.7%. The purity of the extracted AOS was 92.6%. Overall, our work provided new insights for the development of green biotechnologies for oligosaccharide production from seaweed.