Association of IL­6 and MMP­3 gene polymorphisms with adolescent idiopathic scoliosis: A systematic review and meta­analysis.

The pathogenesis of adolescent idiopathic scoliosis (AIS) remains unclear. It has been found that interleukin-6 (IL-6) rs1800795 locus and matrix metalloproteinase-3 (MMP-3) rs3025058 locus gene polymorphisms may be associated with AIS susceptibility, which has been controversial and needs to be further confirmed by updated meta-analysis. The aim of the present study was to investigate the association of MMP-3 rs3025058 and IL-6 rs1800795 single nucleotide polymorphisms (SNPs) with susceptibility to AIS. All relevant articles that met the criteria were retrieved and included, and the publication dates were limited from January 2005 to December 2023. The allele frequencies and different genotype frequencies of IL-6 rs1800795 and MMP-3 rs3025058 loci in each study were extracted and statistically analyzed by ReviewManager 5.4 software, and the odds ratio (OR) and 95% confidence interval (95% CI) of different genetic models were calculated. The results of the meta-analysis showed that there was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS. The allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility (5A vs. 6A, OR=1.18; 95% CI, 1.04-1.33; 5A5A vs. 6A6A, OR=1.65; 95% CI, 1.23-2.21; and 5A5A vs. 5A6A + 6A6A, OR=1.54; 95% CI, 1.19-1.99). Results of subgroup analysis revealed that the allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility in the Caucasian population, and the susceptibility of AIS was associated with the genotype 5A5A of MMP-3 rs3025058 SNP in an Asian population. There was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS, while the allele 5A of MMP-3 rs3025058 locus was associated with the susceptibility to AIS, especially in the Caucasian population.

Lycopodium alkaloids from Huperzia serrata and their cholinesterase inhibitory activities.

Huperzia serrata, belonging to the Lycopodiaceae family, has been traditionally utilized for the management of treating rheumatic numbness, arthritic pain, dysmenorrhea, and contusions. This plant is a rich source of lycopodium alkaloids, some of which have demonstrated notable cholinesterase inhibitory activity. The objective of this study was to identify lycopodium alkaloids with cholinesterase inhibitory properties from H. serrata. The structures of these alkaloids were elucidated by HRESIMS, NMR (including a 1H-15N HMBC experiment), ECD methods and single-crystal X-ray diffraction. The inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were assessed using a modified Ellman's method. Consequently, sixteen lycopodium alkaloids (1-16), including ten previously undescribed ones named huperradines A-G and huperradines I-K (1-7 and 9-11), along with one previously undescribed naturally occurring compound, huperradine H (8), were isolated from H. serrata. Among these, compounds 7 and 1 exhibited potent and moderate AChE inhibition, with IC50 values of 0.876 ± 0.039 µM and 13.125 ± 0.521 µM, respectively. Our results suggest that huperradine G (7) may be a promising lead compound for the development of new AChE inhibitors for Alzheimer's disease.

Lycocasine A, a Lycopodium Alkaloid from Lycopodiastrum casuarinoides and Its Acid-Sensing Ion Channel 1a Inhibitory Activity.

A novel Lycopodium alkaloid, lycocasine A (1), and seven known Lycopodium alkaloids (2-8), were isolated from Lycopodiastrum casuarinoides. Their structures were determined through NMR, HRESIMS, and X-ray diffraction analysis. Compound 1 features an unprecedented 5/6/6 tricyclic skeleton, highlighted by a 5-aza-tricyclic[6,3,1,02,6]dodecane motif. In bioactivity assays, compound 1 demonstrated weak inhibitory activity against acid-sensing ion channel 1a.

In vitro and vivo anti-tumor activity and mechanisms of the new cryptotanshinone derivative 11 against hepatocellular carcinoma.

Global burden of hepatocellular carcinoma (HCC) is increasing. Chemotherapy and immunotherapy are the prevailing options for therapy. Developing new therapeutic strategies for HCC patients is still highly desirable. Recent studies demonstrate that cryptotanshinone is capable of inhibiting tumor growth in HCC and induces antitumor immunity in vitro. In our previous research, we discovered a new cryptotanshinone derivative 11 as an effective immunoregulatory enzyme indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitor. This study aims to evaluate its in vitro and in vivo antitumor activity against hepatocellular carcinoma. 11 displayed robust anti-proliferative activity against HCC cell lines and promoted apoptosis of HCC cell line through the mitochondrial-mediated apoptotic pathway. In H22 tumor-bearing mice models, 11 exhibited significant in vivo anti-tumor activity with different administration routes. And no obvious toxicity was observed. RNA-seq analysis demonstrated the differential expressed genes and alteration of key pathways associated with immune responses after administration of 11. Up-regulation of anti-tumor cytokines and down-regulation of cytokines that promote tumor growth were indicated and further validated. Our study demonstrates that 11 exhibits promising anti-tumor activity both in vitro and in vivo against hepatocellular carcinoma cancer. It is a lead compound for HCC immunotherapy and is worthy for further development.

Accurate prediction bioaccessibility of PAHs in soil-earthworm system by novel magnetic solid phase extraction technique.

Conventional chemical extraction methods may lead to overestimate or underestimate bioaccessibility due to their inability to provide realistic kinetic information regarding PAHs in soils. In this study, we propose the use of magnetic solid phase extraction (MSPE) technique for assessing the bioaccessibility of PAHs in the soil-earthworm system. Firstly, a novel polydopamine-coated magnetic core-shell microspheres (Fe3O4-C16@PDA) was developed by a one-pot sol-gel and self-polymerization method. The PDA coatings not only enhance the hydrophilicity of material surfaces but also exhibit excellent biocompatibility. The maximum adsorption capacity of Fe3O4-C16@PDA for 16 PAHs was 52.72 mg g-1, indicating that the proposed material fulfills the assessment requirements for highly contaminated soil. To compare the measurement of PAHs and their uptake by earthworms (Eisenia fetida), experiments were conducted using four different soils with varying properties. The desorption kinetics data obtained from these experiments demonstrated that the capability of the MSPE in accurately predicting the bioavailable portions of PAHs. After a 28-day exposure, the best predictor of bioavailable PAHs in earthworms was MSPE method exhibited the highest correlation coefficient (R2 > 0.90), and its slopes in the four soils were 0.972, 0.961, 1.012, and 0.962, respectively, all close to 1. These results demonstrate that the MSPE method successfully mimics the conditions encountered in soil-earthworm systems and effectively assess bioaccessibility of PAHs in soils.

Unified Strategy Enables the Collective Syntheses of Structurally Diverse Indole Alkaloids.

Natural products and their analogues are significant sources of therapeutic lead compounds. However, synthetic strategies for generating large collections of these molecules remain a significant challenge. The most difficult step in their synthesis is the design of a common intermediate that can be easily transformed into natural products belonging to different families. This study demonstrates the evolution of synthetic tactics designed to assemble the functionalized piperidines present in indole alkaloids from a common intermediate. More importantly, we also report a previously unknown Ir- and Er-catalyzed dehydrogenative spirocyclization reaction that enables direct access to spirocyclic oxindole alkaloids. As a practical application, the asymmetric total syntheses of 29 natural alkaloids belonging to different families were accomplished by following a uniform synthetic route. The proposed methodology extends the capability of the iridium-catalyzed dehydrogenative coupling reaction to the realm of indole-alkaloid synthesis and provides new opportunities for the efficient preparation of natural product-like molecules.

Comparison between minimally invasive and open transforaminal lumbar interbody fusion for the treatment of multi­segmental lumbar degenerative disease: A systematic evaluation and meta­analysis.

The present study aimed to compare the differences between minimally invasive transforaminal lumbar fusion (MIS-TLIF) and open transforaminal lumbar fusion (TLIF) for multi-segmental lumbar degenerative disease regarding intraoperative indices and postoperative outcomes. PubMed, Web of Science, Embase, CNKI, Wanfang and VIP databases were searched for literature on MIS-TLIF and open TLIF in treating multi-segmental lumbar degenerative diseases. Of the 1,608 articles retrieved, 10 were included for final analysis. The Newcastle-Ottawa Scale and Review Manager 5.4 were used for quality evaluation and data analysis, respectively. The MIS-TLIF group was superior to the open TLIF group regarding intraoperative blood loss [95% confidence interval (CI): -254.33,-157.86; P<0.00001], postoperative in-bed time (95%CI: -3.49,-2.76; P<0.00001), hospitalization time (95%CI: -5.14,-1.78; P<0.0001) and postoperative leg pain Visual Analog Scale score (95%CI: -0.27,-0.13; P<0.00001). The fluoroscopy frequency for MIS-TLIF (95%CI: 2.07,6.12; P<0.0001) was significantly higher than that for open TLIF. The two groups had no significant differences in operation time, postoperative drainage volume, postoperative complications, fusion rate, or Oswestry Disability Index score. In treating multi-segmental lumbar degenerative diseases, MIS-TLIF has the advantages of less blood loss, shorter bedtime and hospitalization time and improved early postoperative efficacy; however, open TLIF has a lower fluoroscopy frequency.

Taxodin A, a Cytotoxic C30 Terpenoid from Taxodium mucronatum with a Unique Skeleton.

Taxodin A (1), a unique C30 terpenoid featuring an unprecedented skeleton composed of an abietane-type diterpene and a menthane-type monoterpene, was obtained from the leaves and branches of Taxodium mucronatum. The structure and absolute configuration of compound 1 was unequivocally established by the combination of extensive spectroscopic analyses and X-ray single-crystal diffraction analysis. Compound 1 exhibited potent cytotoxic activities against A549, SMMC-7721, MDA-MB-231, and SW480 cell lines with IC50 values of 15.35±0.73, 8.49±0.35, 17.53±0.79, 18.93±0.60 µM, respectively.

Gastrodinol derivatives and prenylated flavones from the flower branch of Gastrodia elata.

Based on the research progress and traditional usage with whole herbal of the TCM "Tianma", chemical studies herein on the flower branch of Gastrodia elata were carried out in-depth and got 13 compounds including the gastrodinols (1-4), the flavonoid morins (5-8, 11-12), together with the specialist mulberrofurans (9, 13) and gastrodiamide (10) for the first time from the species. The antibacterial and cholinesterase inhibitory activities were then evaluated and the results showed that compounds 5, 11, 12, 13 have good activity against anti-methicillin-resistant Staphylococcus aureus, and compounds 9, 13 had good acetylcholinesterase inhibitory activity. All these results provide new chemical composition for better understanding the traditional application of "Tianma" and for exploring new pharmacological ingredients.

Discovery of α-Obscurine Derivatives as Novel Cav3.1 Calcium Channel Blockers.

Voltage-gated calcium channels (VGCCs), particularly T-type calcium channels (TTCCs), are crucial for various physiological processes and have been implicated in pain, epilepsy, and cancer. Despite the clinical trials of TTCC blockers like Z944 and MK8998, none are currently available on the market. This study investigates the efficacy of Lycopodium alkaloids, particularly as natural product-based TTCC blockers. We synthesized eighteen derivatives from α-obscurine, a lycodine-type alkaloid, and identified five derivatives with significant Cav3.1 blockade activity. The most potent derivative, compound 7, exhibited an IC50 value of 0.19±0.03 µM and was further analyzed through molecular docking, revealing key interactions with Cav3.1. These findings provide a foundation for the structural optimization of Cav3.1 calcium channel blockers and present compound 7 as a promising lead compound for drug development and a tool for chemical biology research.

Lycopodium Alkaloids from Huperzia goebelii.

One new fawcettimine-type Lycopodium alkaloid, hupertimine F (1), together with five known (2-6) Lycopodium alkaloids were isolated from Huperzia goebelii. The structure of 1 was elucidated by 1D and 2D NMR spectra, HRESIMS, and X-ray diffraction. Structurally, 1 represents the fourth example of Lycopodium alkaloids characterized by a 5/5/5/5/6 pentacyclic ring system with a 1-aza-7-oxabicyclo[2.2.1]heptane moiety. These known compounds 2, 3, 5, and 6 were isolated from H. goebelii for the first time. Compounds 1-6 were evaluated for acetylcholinesterase, butyrylcholinesterase and monoamine oxidase B inhibitory activities in vitro.

Two new sesquiterpene glycosides from the stems of Dendrobium henanense and their anti-inflammatory activity.

Two new sesquiterpene glycosides, 8α,12,15ß-trihydroxycopacamphan-15-O-ß-D-glucopyranoside (1) and dendrobiumane C-11-O-ß-D-glucopyranoside (2), along with three known terpenoids (3-5) were isolated from the aerial stems of Dendrobium henanense. Their structures were elucidated based on NMR-spectroscopic and HR-MS analyses. All compounds could reduce the levels of NO, TNF-α and IL-1ß in LPS-induced RAW264.7 cells with IC50 values ranging from 10.37 to 34.55 µΜ.

Casuattimines A-N, fourteen new Lycopodium alkaloids from Lycopodiastrum casuarinoides with Cav3.1 channel inhibitory activity.

Two new dimeric Lycopodium alkaloids, casuattimines A and B (1 and 2), along with twelve previously undescribed Lycopodium alkaloids, casuattimines C-N (3-14), and eight known Lycopodium alkaloids, were isolated from Lycopodiastrum casuarinoides. Casuattimines A and B (1 and 2) are the first two ether-linked Lycopodium alkaloid dimers. Casuattimines C and D (3 and 4) are unique Lycopodium alkaloids characterized by a long fatty acid chain. Structural elucidation was achieved through HRESIMS, NMR, and electronic circular dichroism (ECD) calculations. In addition, the absolute configurations of compounds 7, 13, and 14 were determined by single crystal X-ray diffraction. Compounds 1, 2, and 4 demonstrated notable Cav3.1 channel inhibitory activities presenting IC50 values of 10.75 ± 1.02 µM, 9.33 ± 0.79 µM, and 7.14 ± 0.86 µM, respectively. The dynamics of compound 4 against the Cav3.1 channel and preliminary structure-activity relationships of these active Lycopodium alkaloids were also discussed.

Enantioselective Access to Chiral 2,5-Diketopiperazines via Stereogenic-at-Cobalt(III)-Catalyzed Ugi-4CRs/Cyclization Sequences.

An asymmetric synthesis of chiral 2,5-diketopiperazines by the Ugi-4CR/cyclization is exhibited. The employment of catalytic anionic chiral Co(III) complexes delivered α-propiolyl aminoamides in high yields with excellent enantioselectivities (31 examples, up to 95% ee). The following treatment of Ugi-adducts with PPh3 leads to chiral 2,5-DKPs without significant loss of enantioselectivities (26 examples, up to 91% ee).

The association of growth differentiation factor 5 rs143383 gene polymorphism with osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Osteoarthritis (OA) is caused by a complex set of pathophysiological factors. The genetic factors involved in the occurrence and progress of the disease have been widely discussed by scholars. It was found that growth differentiation factor 5 (GDF5) gene polymorphisms may be linked to OA susceptibility, which has been controversial and needs to be further confirmed by an updated meta-analysis. OBJECTIVES: We examined the association between GDF5 rs143383 single nucleotide polymorphism (SNP) and OA susceptibility. METHODS: All relevant articles that met the criteria are retrieved and included, and the search deadline is June 2022. The allele frequencies and different genotype frequencies of GDF5 rs143383 loci in each study were extracted and statistically analyzed by R4.1.3 software, and the different genetic models were analyzed based on their odds ratio (OR) and 95% confidence interval (CI). RESULTS: The meta-analysis explained that GDF5 rs143383 SNP was crucial correlated with OA in all patients with OA of knee, hip and hand. The codominant gene model in the whole crowd (OR = 1.17, 95% CI 1.07-1.27, P < 0.01) enlightened that OA was vitally associated with GDF5 gene polymorphism. At the same time, we did a subgroup analysis based on ethnicity. The codominant gene model (OR = 1.31, 95% CI 1.12-1.53, P < 0.01) in Asian population, the codominant homozygote model (OR = 1.28, 95% CI 1.14-1.43), codominant heterozygote gene model (OR = 1.12, 95% CI 1.01-1.23, P = 0.02), and dominant gene model (OR = 1.19, 95% CI 1.09-1.31, P < 0.01) in Caucasian are analyzed by subgroup analysis. It means that there is a momentous relationship between the GDF5rs143383 gene polymorphism and OA, especially among Caucasians. In addition, we also discussed different types of OA separately and discover that the GDF5rs143383 gene polymorphism was relevant for knee osteoarthritis (KOA) and hand osteoarthritis, and it was more significant in the Caucasian population. But due to the high heterogeneity in hip osteoarthritis, it could not be accurately concluded. Furthermore, we also analyzed the osteoarthritis of different genders and found that the GDF5 rs143383 SNP was associated with both men and women and was still significant in the Caucasian population. CONCLUSION: We found a close association between osteoarthritis and GDF5rs143383SNP in this study. From the analysis of each group, we got the same conclusion in KOA and hand OA, but which need further verification in hip OA. Considering gender, we found a close relationship between GDF5 rs143383 SNP and OA of the knee, hip and hand, both for men and women. This conclusion is more obvious in Caucasian people.

A rare presentation of Maffucci syndrome: A case report and literature review.

Maffucci syndrome is an extremely rare disease which can manifest symptoms as early as childhood. It is estimated that there have been <300 cases reported globally; however, this number is likely to be an underestimate. Maffucci syndrome is characterized by multiple enchondromas and soft tissue hemangiomas, which can cause growth and developmental malformations. In addition to bone deformities, pathological fractures and a loss of mobility, patients with Maffucci syndrome may develop secondary central chondrosarcoma and have a higher risk of developing non-skeletal malignant tumors, such as gliomas and mesenchymal ovarian tumors. The present study provides information for clinicians about this disease through the use of imaging, physical examinations, clinical manifestations and the treatment strategy used. There is need to summarize the existing cases of this disease around the world and produce an effective framework for the diagnosis, treatment and prevention of Maffucci syndrome, in order to better understand this disease. The present study reports on a 15-year-old male diagnosed with Maffucci syndrome. . Due to the risk of malignant tumor development in the absence of effective treatment, regular and careful observation through monitoring of tumor markers and imaging studies is important for patients with Maffucci syndrome. As cases of this disease are rare and case data is limited, it is difficult to create a clear treatment plan. There is an urgent need to establish a case database of Maffucci syndrome patients and explore its pathogenesis for early diagnosis, treatment and prevention of disease.

Discovery and Biomimetic Semisynthesis of Spirophyllines A-D from Uncaria rhynchophylla.

Spirophyllines A-D (1-4), four new spirooxindole alkaloids all characterized by the spiro[pyrrolidin-3,3'-oxindole] core and a rare isoxazolidine ring, were isolated from Uncaria rhynchophylla. Their structures were determined by spectroscopic methods and confirmed by X-ray crystallography. Based on the biomimetic semisynthesis strategy, compounds 1-8 were synthesized in three steps via the key reactions of 1,3-dipolar cycloaddition and Krapcho decarboxylation from corynoxeine. Interestingly, compound 3 showed moderate inhibitory activity against the Kv1.5 potassium channel (IC50 = 9.1 µM).

Efficacy and safety of unilateral biportal endoscopy compared with microscopic decompression in the treatment of lumbar spinal stenosis: A systematic review and updated meta­analysis.

The incidence of lumbar spinal stenosis is increasing annually, and with an ever-aging population and longer life expectancies, this trend will further continue. It is hoped that a more effective treatment can be found so that the patients can be relieved of their pain. The aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of unilateral biportal endoscopic surgery (UBE) and microscopic decompression surgery (MD) for the treatment of lumbar spinal stenosis. A literature search of related studies published until April 2022 was performed using PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, Google Scholar, China National Knowledge Infrastructure (CNKI), and other databases. After filtering of references, 12 eligible studies were identified that compared UBE with MD as a treatment for lumbar spinal stenosis. Data were extracted and analysed using R. A total of 12 articles (four randomized controlled and eight cohort studies) were included, with a total of 1,067 patients: 250 men and 249 women in the UBE group and 290 men and 278 women in the MD group. The meta-analysis showed that the mean intraoperative blood loss in the UBE group [standardized mean difference (SMD)=-2.10, 95% confidence interval (CI) (-3.97, -0.23), P=0.03] was lower than that in the MD group. The postoperative Visual analogue scale (VAS) score for back pain [SMD=-0.52, 95% CI (-0.76, -0.27), P<0.01], leg pain [SMD=-0.30, 95% CI (-0.51, -0.08), P<0.01], postoperative Oswestry disability index [(ODI); SMD=-0.25, 95% CI (-0.48, -0.03), P=0.03], and postoperative C-reactive protein [(CRP); odds ratio (OR)=-0.92, 95% CI (-1.80, 0.03), P=0.04] were lower than those in the MD group. Complications (OR=0.60, 95% CI (0.37, 0.98), P=0.04) and hospital stay (SMD=-1.84, 95% CI (-2.85, 0.83), P <0.01] were also lesser in the UBE group than in the MD group. UBE was preferable to that in the MD group according to the modified MacNab score [OR=2.28, 95% CI (1.28, 4.06), P<0.01]. No significant differences were observed in the operation times between the groups. UBE surgery was found to be a better option for the treatment of lumbar spinal stenosis than MD surgery.

Voluntary Deep Inspiration Breath-Hold (VDIBH) Whole-Breast Irradiation Assisted by Optical Surface Monitoring System (OSMS) in Patients With Left-Sided Breast Cancer: A Prospective Phase II Study.

Objectives: To investigate the dosimetric advantages of the voluntary deep inspiration breath-hold technique assisted by optical surface monitoring system for whole breast irradiation in left breast cancer after breast-conserving surgery and verify the reproducibility and acceptability of this technique. Methods: Twenty patients with left breast cancer receiving whole breast irradiation after breast-conserving surgery were enrolled in this prospective phase II study. Computed tomography simulation was performed during both free breathing and voluntary deep inspiration breath-hold for all patients. Whole breast irradiation plans were designed, and the volumes and doses of the heart, left anterior descending coronary artery, and lung were compared between free breathing and voluntary deep inspiration breath-hold. Cone beam computed tomography was performed for the first 3 treatments, then weekly during voluntary deep inspiration breath-hold treatment to evaluate the accuracy of the optical surface monitoring system technique. The acceptance of this technique was evaluated with in-house questionnaires completed by patients and radiotherapists. Results: The median age was 45 (27-63) years. All patients received hypofractionated whole breast irradiation using intensity-modulated radiation therapy up to a total dose of 43.5 Gy/2.9 Gy/15f. Seventeen of the 20 patients received concomitant tumor bed boost to a total dose of 49.5 Gy/3.3 Gy/15f. Voluntary deep inspiration breath-hold showed a significant decrease in the heart mean dose (262 ± 163 cGy vs 515 ± 216 cGy, P < .001) and left anterior descending coronary artery (1191 ± 827 cGy vs 1794 ± 833 cGy, P < .001). The median delivery time of radiotherapy was 4 (1.5-11) min. The median deep breathing cycles were 4 (2-9) times. The average score for acceptance of voluntary deep inspiration breath-hold by patients and radiotherapists was 8.7 ± 0.9 (out of 12) and 10.6 ± 3.2 (out of 15), respectively, indicating good acceptance by both. Conclusions: The voluntary deep inspiration breath-hold technique for whole breast irradiation after breast-conserving surgery in patients with left breast cancer significantly reduces the cardiopulmonary dose. Optical surface monitoring system-assisted voluntary deep inspiration breath-hold is reproducible and feasible and showed good acceptance by both patients and radiotherapists.

Corrigendum: Diagnostic efficiency of metagenomic next-generation sequencing for suspected spinal tuberculosis in China: a multicenter prospective study.

[This corrects the article DOI: 10.3389/fmicb.2022.1018938.].