Vitamin D and Its Receptors in Cervical Cancer.

Several studies have investigated the relationship between vitamin D (VD) and its receptors (VDR) and the risk of cervical cancer. However, the underlying mechanisms that underpin these associations remain incompletely comprehended. In this review, we analyzed the impacts of VD and VDR on cervical cancer and related mechanisms, and discussed the effects of VD, calcium, and other vitamins on cervical cancer. Our literature research found that VD, VDR and their related signaling pathways played indispensable roles in the occurrence and progression of cervical cancer. Epidemiological studies have established associations between VD, VDR, and cervical cancer susceptibility. Current studies have shown that the inhibitory effect of VD and VDR on cervical cancer may be attributed to a variety of molecules and pathways, such as the EAG potassium channel, HCCR-1, estrogen and its receptor, p53, pRb, TNF-α, the PI3K/Akt pathway, and the Wnt/ß-catenin pathway. This review also briefly discussed the association between VDR gene polymorphisms and cervical cancer, albeit a comprehensive elucidation of this relationship remains an ongoing research endeavor. Additionally, the potential ramifications of VD, calcium, and other vitamins on cervical cancer has been elucidated, yet further exploration into the precise mechanistic underpinnings of these potential effects is warranted. Therefore, we suggest that further studies should focus on explorations into the intricate interplay among diverse molecular pathways and entities, elucidation of the mechanistic underpinnings of VDR polymorphic loci changes in the context of HPV infection and VD, inquiries into the mechanisms of VD in conjunction with calcium and other vitamins, as well as investigations of the efficacy of VD supplementation or VDR agonists as part of cervical cancer treatment strategies in the clinical trials.

Effect of acupressure in nausea and vomiting treatment during pregnancy: A meta-analysis.

BACKGROUND AND OBJECTIVE: Many women experience nausea and vomiting in early pregnancy. Regardless of the disease severity, it affects the work and life of pregnant women. However, drug treatment may potentially impact the foetus; thus, alternative safe and effective measures are essential. We aimed to evaluate the effect of acupressure, a non-drug treatment for nausea and vomiting, during pregnancy. METHODS: PubMed, EMBASE, Cochrane, Web of Science, CNKI, CBM, VIP, and Wanfang databases were searched using 'pregnancy', 'nausea', 'vomiting', and 'acupressure' as keywords. The search period was from database inception to 30 November 2022. Two researchers independently screened articles, extracted data, and used RevMan 5.4 software for statistical analysis. RESULTS: We included 33 trials and 3 390 patients in this meta-analysis. Acupressure was effective for women with nausea and vomiting during pregnancy (odds ratio (OR)= 4.81, 95% confidence interval (CI) [3.47, 6.68]; p<0.0001); it significantly reduced the nausea score of the Rhodes index (mean square deviation (MD): -3.21, 95% CI [-4.85, -1.57], Z = 3.83, p = 0.0001), modified Pregnancy Unique Quantification of Emesis and Nausea score (MD: -2.18, 95% CI [-3.21, -1.15], Z = 4.15, p<0.0001), and hospital stay (OR=-3.27, 95% CI [-6.18, -0.36]; p = 0.03) and improved quality of life (MD: -14.06,95% CI [- 17.31, -10.18], Z = 8.48, p<0.00001). However, no significant difference was observed in nursing satisfaction and anxiety scores (OR=4.13, 95% CI [0.89, 19.15]; p = 0.07) (MD: -13.26,95% CI [-32.04,5.53], Z = 1.38, p = 0.17). CONCLUSIONS: This meta-analysis provides evidence of a non-drug intervention for women with nausea and vomiting during pregnancy; acupressure effectively reduces nausea and vomiting during pregnancy.

LncRNA GAS5 Suppresses Colorectal Cancer Progress by Target miR-21/LIFR Axis.

GAS5 is abnormally high in colorectal cancer tissues, which is a specific expression of lncRNA in colorectal cancer (CRC). Nevertheless, its biological function in CRC has not been elucidated. The abnormal high expression of GAS5 in CRC is the specific expression of lncRNA in CRC. The purpose of our study is to explore the effect of GAS5 on CRC and its mechanism. The expression of GAS5 in 53 paired normal and colorectal cancer tissues and colorectal cancer cell lines was detected by real-time PCR. The biological effects of GAS5, miR-21, and LIFR were measured by functional assays, including wound healing, transwell assays, and in vivo assays. We ensured the carcinogenesis role of GAS5 in CRC in the xenograft nude model. The dual-luciferase reporter assay system and chromatin immunoprecipitation method were used for target evaluation and Western blot for verification. GAS5 was significantly decreased in tumor tissues and CRC cells, and the low expression of CAS5 in CRC promoted tumor metastasis and decreased the survival of patients. GAS5 knockdown increases the cell viability, inhibits apoptosis, and promotes migration. Xenografted tumors in nude mice studies showed that GAS5 knockdown promoted tumor growth and caused worse lesions in colorectal. Furthermore, GAS5 increases the expression level of target gene LIFR to promote the apoptosis of CRC cells by binding to miR-21. Our study revealed that a novel pathway about lncRNA GAS5 inhibited the proliferation and metastasis of CRC cells by targeting miR-21/LIFR which provides a new strategy to treat CRC.

Autologous Platelet-Rich Gel for the Treatment of Diabetic Sinus Tract Wounds: A Clinical Study.

BACKGROUND: The aim of this study was to evaluate the efficacy of autologous platelet-rich gel (APG) in the treatment of deep sinus tract wounds from diabetic ulcers. METHODS: Forty-eight patients with diabetic ulcers were randomly classified into two groups: an APG treatment group (25 patients) and a conventional wound dressing control group (23 patients). The sinus tract closure times, ulcer healing rates, hospitalization times, and hospitalization expenses of the two groups were compared. RESULTS: There were no significant differences in the basic data and wound conditions between the two groups. The cure (healed wound) rates were 96% and 87% for the APG group and control group, respectively. During the first 4 wk, the sinus tract closure rate for the APG group was significantly higher than that for the control group. However, there was no significant difference in the sinus tract healing between the two groups at the end of the 8th wk. For the APG group and the control group, the average hospital stays were 19.36 ± 7.239 d and 48.13 ± 11.721 d, respectively, and the total hospitalization expenses were 2.48 ± 0.45 ten thousand yuan and 5.63 ± 1.35 ten thousand yuan (P < 0.05), respectively. These differences were statistically significant. CONCLUSIONS: When compared with conventional wound dressings, APG can accelerate the healing of deep sinus tract wounds associated with diabetic ulcers.

Conbercept for patients with age-related macular degeneration: a systematic review.

BACKGROUND: Conbercept is a novel vascular endothelial growth factor (VEGF) inhibitor for the treatment of wet age-related macular degeneration (AMD). This systematic review aims to assess the efficacy and safety of conbercept in the treatment of wet AMD. METHODS: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP database, and Wanfang database were searched from their earliest records to June 2017. We included randomized controlled trials (RCTs) evaluating the efficacy and safety of conbercept in wet AMD patients. Outcomes included the mean changes from baseline in best-corrected visual acuity (BCVA) score (primary outcome), central retinal thickness (CRT), plasma level of vascular endothelial growth factor (VEGF) over time, and the incidence of adverse events (AEs). RESULTS: Eighteen RCTs (1285 participants) were included in this systematic review. Conbercept might improve BCVA compared to triamcinolone acetonide [MD = 0.11, 95% CI (0.08, 0.15)], and reduce CRT compared to the other four therapies (conservative treatment, ranibizumab, transpupillary thermotherapy, and triamcinolone acetonide). The incidence of AEs in patients receiving conbercept was significantly lower than those receiving triamcinolone acetonide [RR = 0.25, 95% CI (0.09-0.72)], but was similar to the other therapies. Conbercept seemed to be more effective than ranibizumab in lowering the plasma level of VEGF [MD = - 15.86, 95% CI (- 23.17, - 8.55)]. CONCLUSIONS: Current evidence shows that conbercept is a promising option for the treatment of wet AMD. Nevertheless, further studies are required to compare the efficacy, long-term safety and cost-effectiveness between conbercept and other anti-VEGF agents in different populations.

Scorpion inhibits epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most malignant diseases worldwide. The unfavorable clinical outcome and poor prognosis are due to high rates of recurrence and metastasis after treatments. Some scholars of traditional Chinese medicine suggested that endogenous wind-evil had played an important role in metastasis of malignant tumor. Therefore, the drug of dispelling wind-evil could be used to prevent cancer metastasis and improve the poor prognosis. So we wondered whether Scorpion, one of the most important wind calming drugs, has antitumor effect especially in epithelial-mesenchymal transition (EMT) and metastasis of HCC in this research. We found that Scorpion-medicated serum could inhibit proliferation, induce apoptosis, and decrease migration and invasion capacity of Hepa1-6 cells in vitro. Meanwhile, we observed that water decoction of Scorpion restrained tumor growth and metastasis in nude mouse of HCC metastasis models. Further experiments showed that Scorpion could suppress EMT, which is characterized by increased epithelial marker E-cadherin expression and decreased mesenchymal markers N-cadherin and Snail expression following Scorpion treatment both in vitro and in vivo. These results suggested that the Scorpion could inhibit Hepa1-6 cells' invasion and metastasis in part by reversing EMT and providing a possible potential approach for preventing HCC metastasis. Impact statement The unfavorable clinical outcome and poor prognosis of hepatocellular carcinoma (HCC) are due to high rates of recurrence and metastasis after treatments. Here we found Scorpion, one of the most important wind calming drugs, has antitumor effect. Scorpion-medicated serum inhibited the proliferation, induced apoptosis, and decreased migration and invasion capacity of Hepa1-6 cells in vitro. Water decoction of Scorpion restrained tumor growth and metastasis in nude mouse of HCC metastasis models. Further experiments showed that Scorpion could suppress EMT of HCC both in vitro and in vivo. Our results suggested that the Scorpion could inhibit Hepa1-6 cells' invasion and metastasis in part by reversing EMT and providing a possible potential approach for preventing HCC metastasis.

Preparation of Galla Chinensis Oral Solution as well as Its Stability, Safety, and Antidiarrheal Activity Evaluation.

BACKGROUND OF THE STUDY: As a widely used traditional medicine, Galla Chinensis is rich in tannins. However, there are few detailed studies about pharmaceutical preparations of Galla Chinensis tannin extract (GTE). In the present experiments, for better application and to investigate the possibility that Galla Chinensis tannin extract can be used as an antidiarrheal drug, we prepared Galla Chinensis oral solution (GOS). MATERIALS AND METHODS: GOS was prepared with GTE, and its physicochemical and microbiological stability was evaluated. The oral acute toxicity of GOS was calculated by the 50% lethal dose (LD50). The antidiarrheal activity was determined in a castor oil-induced diarrhea model in mice through diarrhea symptoms, fluid accumulation ratio, and percentage of distance moved by charcoal meal. RESULTS: The tannin content of GTE was 47.75%. GOS could endure a high temperature without a significant decrease of tannin content. After storage for six months, the tannin content of GOS was still more than 90%. GOS was determined to be nontoxic. Meanwhile, GOS showed significant antidiarrheal activity in a castor oil-induced diarrhea model in mice (P < 0.01). CONCLUSION: The results suggested that GOS is an effective and stable antidiarrheal drug that can be used to complement other therapies.

The Traditional Chinese Medicine and Relevant Treatment for the Efficacy and Safety of Atopic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Atopic dermatitis (AD) has become a common skin disease that requires systematic and comprehensive treatment to achieve adequate clinical control. Traditional Chinese medicines and related treatments have shown clinical effects for AD in many studies. But the systematic reviews and meta-analyses for them are lacking. OBJECTIVE: The systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were conducted to evaluate the efficacy and safety of traditional Chinese medicines and related treatments for AD treatment. METHODS: Randomized controlled trials (RCTs) were searched based on standardized searching rules in eight medical databases from the inception up to December 2016 and a total of 24 articles with 1,618 patients were enrolled in this meta-analysis. RESULTS: The results revealed that traditional Chinese medicines and related treatments did not show statistical differences in clinical effectiveness, SCORAD amelioration, and SSRI amelioration for AD treatment compared with control group. However, EASI amelioration of traditional Chinese medicines and related treatments for AD was superior to control group. CONCLUSION: We need to make conclusion cautiously for the efficacy and safety of traditional Chinese medicine and related treatment on AD therapy. More standard, multicenter, double-blind randomized controlled trials (RCTs) of traditional Chinese medicine and related treatment for AD were required to be conducted for more clinical evidences providing in the future.

A systematic review and meta-analysis of traditional insect Chinese medicines combined chemotherapy for non-surgical hepatocellular carcinoma therapy.

On the background of high morbidity and mortality of hepatocellular carcinoma (HCC) and rapid development of traditional Chinese medicine (TCM), we conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to assess the clinical effectiveness and safety of traditional insect Chinese medicine and related preparation for non-surgical HCC. RCTs were searched based on standardized searching rules in mainstream medical databases from the inception up to May 2016. Ultimately, a total of 57 articles with 4,651 patients enrolled in this meta-analysis. We found that traditional insect Chinese medicine and related preparation combined chemotherapy show significantly effectiveness and safety in objective response rate (P < 0.001), survival time extension [12 months (P < 0.001); 18 months (P < 0.001); 24 months (P < 0.001); 36 months (P < 0.001)], amelioration for life quality [QoL scores improvement (P < 0.001); KPS improvement (P < 0.001); AFP improvement (P < 0.001)] and reduction of therapeutic toxicity [WBC decrease (P = 0.04); gastrointestinal adverse reactions (P < 0.001)]. In conclusion, traditional insect Chinese medicine and related preparations could be recommended as auxiliary therapy combined chemotherapy for HCC therapy.

Clinical features and outcome in patients with osseomuscular type of Wilson's disease.

BACKGROUND: Wilson's disease with osseomuscular type is a rare condition, which often lacks typical hepatic and neurological symptoms and causes misdiagnoses easily. During the past 10 years, eight Chinese patients of osseomuscular type of Wilson's disease were identified in our clinic. METHODS: Clinical information was gathered from medical records and follow-ups. The genetic testing was performed in each patient. Serum ceruloplasmin, Kayser-Fleischer rings, liver function, brain magnetic resonance imaging and abdominal ultrasonography were also evaluated. RESULTS: The median age of onset is 12 years of age. The patients had their initial musculoskeletal conditions with arthralgia or joint deformity, while the hepatic or neurologic signs were minimal. Most patients (6/8) eventually developed clinical neurological symptoms afterwards with a median interval of 36 months. All of them had normal liver function and low serum ceruloplasmin (<0.1 g/L). Most patients (6/8) present with Kayser-Fleischer rings and abnormal hepatic ultrasonography. The arthralgia was resolved with copper chelation therapy. CONCLUSIONS: Wilson's disease with osseomuscular type occurs without typical hepatic or neurological symptoms, which makes the clinical diagnosis challenging. Serum ceruloplasmin, abdominal ultrasonography, ophthalmic examination and genetic testing help to establish the diagnosis. Early diagnosis can initiate an effective treatment and prevent the further damage.

Simultaneous Determination of 10 Adulterants in Antihypertensive Functional Foods Using Multi-Walled Carbon Nanotubes-Dispersive Solid-Phase Extraction Coupled with High Performance Liquid Chromatography.

Consumption of functional foods based on extracts from selected herbs to alleviate hypertension is an increasingly common practice in China. Adulteration of these foods with pharmaceuticals can significantly impact a consumer's health. To control the quality of the functional foods effectively, a method for the simultaneous determination of 10 common adulterants including chlortalidone, hydrochlorothiazide, indapamide, metoprolol, nifedipine, nimodipine, nitrendipine, reserpine, triamterene and valsartan in antihypertensive functional foods was developed. The target chemicals in samples were ultrasonically extracted with acetonitrile, and then cleaned-up with multi-walled carbon natotubes-dispersive solid-phase extraction. Finally, the analytes were separated with a C18 column using binary mobile phases consisting of acetonitrile and 0.03 mol/L KH2PO4 solutions (pH 3.0). The flow rate of the mobile phase was 0.80 mL/min, and the column temperature was 35°C. The detection wavelength was set at 220 nm. The limits of detection and quantification of the method ranged from 0.014 to 0.053 and 0.047 to 0.178 µg/mL, respectively. The recoveries of the method were in the range of 80.1-98.1% with relative standard deviations <9.53%. The method was successfully applied to the determination of the target chemicals in real samples and simulated samples, and respirine was detected in one tonic wine sample with a concentration of 56.8 ± 1.2 mg/L.

HIF-1α signaling activation by post-ischemia treatment with astragaloside IV attenuates myocardial ischemia-reperfusion injury.

In this study, we evaluated the effect of astragaloside IV (Ast IV) post-ischemia treatment on myocardial ischemia-reperfusion (IR) injury (IRI). We also examined whether hypoxia inducible factor-1α (HIF-1α) and its downstream gene-inducible nitric oxide (NO) synthase (iNOS) play roles in the cardioprotective effect of Ast IV. Cultured cardiomyocytes and perfused isolated rat hearts were exposed to Ast IV during reperfusion in the presence or absence of the HIF-1α inhibitor 2-methoxyestradiol (2-MeOE2). The post-ischemia treatment with Ast IV protected cardiomyocytes from the apoptosis and death induced by simulated IRI (SIRI). Additionally, in cardiomyocytes, 2-MeOE2 and HIF-1α siRNA treatment each not only abolished the anti-apoptotic effect of post-ischemia treatment with Ast IV but also reversed the upregulation of HIF-1α and iNOS expression. Furthermore, after treatment with Ast IV, post-ischemic cardiac functional recovery and lactate dehydrogenase (LDH) release in the coronary flow (CF) were improved, and the myocardial infarct size was decreased. Moreover, the number of apoptotic cells was reduced, and the upregulation of the anti-apoptotic protein Bcl2 and downregulation of the pro-apoptotic protein Caspase3 were reversed. 2-MeOE2 reversed these effects of Ast IV on IR-injured hearts. These results suggest that post-ischemia treatment with Ast IV can attenuate IRI by upregulating HIF-1α expression, which transmits a survival signal to the myocardium.

[Correlation study on 12p13 single nucleotide polymorphism rs12425791 and Chinese medical syndrome types in ischemic stroke patients of the Han nationality].

OBJECTIVE: To explore the correlation between 12p13 single nucleotide polymorphism (SNP) rs12425791 and Chinese medical syndrome types of ischemic stroke patients of the Han nationality. METHODS: A case-control study was used. Recruited were 148 ischemic stroke patients of the Han nationality (67 patients of phlegm syndrome and 81 patients of blood stasis syndrome). Another 192 healthy subjects were recruited as the control group. The genotypes of rs12425791 were performed by TaqMan SNP genotyping assays to analyze the distribution of genes and the distribution frequency of alleles. RESULTS: There was no statistical difference in the genotype and alleles of rs12425791 between the ischemic stroke patients of phlegm syndrome and the control group, or between the ischemic stroke patients of blood stasis syndrome and the control group (P > 0.05). CONCLUSION: Our results did not support that 12p13 common variant rs12425791 was correlated with the pathogeneses of ischemic stroke patients of phlegm syndrome and ischemic stroke patients of blood stasis syndrome.

The clinical value of sonourethrography after bipolar transurethral plasmakinetic prostatectomy.

The aim of this study was to assess the value of transrectal sonourethrography in the diagnosis of dysuria after bipolar transurethral plasmakinetic prostatectomy (TUPKP). Seventy-seven male patients with dysuria after TUPKP underwent transrectal sonourethrography. The clinical data were then compared with the surgical outcomes. The following pathologies were diagnosed: Bladder neck atresia (17/77), bladder orifice strictures (15/77), membranous urethral strictures (21/77), pars cavernosa urethral stricture (12/77), residual prostate gland (5/77), external urethral orifice stricture (2/77), calculi in the prostatic urethra (2/77), flap in the internal urethral orifice (2/77), and postoperative dysfunction of the bladder detrusor muscle (1/77). Transrectal sonourethrography is a reliable diagnostic method for numerous pathologies that occur in patients with dysuria after TUPKP and is a clinically useful tool.

[Inhalation of aerosolized perfluorocarbon combined with tetramethylpyrazine ameliorates hemodynamics and pulmonary histopathology in a porcine model of acute lung injury].

OBJECTIVE: To observe the effect of inhalation of aerosolized perfluorocarbon combined with tetramethylpyrazine on the hemodynamics and histopathology in a porcine model of acute lung injury. METHODS: Normal adult pigs were subjected to saline lavage of the bilateral lungs to induce acute lung injury and randomized subsequently into 3 groups for treatment with inhalation of perfluorocarbon, combined inhalation of perfluorocarbon and tetramethylpyrazine, or inhalation of tetramethylpyrazine. The changes of mean arterial pressure (MAP), PetCO(2), mPAP, CVP and PAWP were recorded at different time points following the lung injury, and the lung tissues were sampled for histological observations. RESULTS: The MAP, mPAP, CVP and PAWP all increased significantly in the 3 groups after acute lung injury. Interventions with combined tetramethylpyrazine and perfluorocarbon inhalation significantly improved these indices as compared with inhalation of tetramethylpyrazine or perfluorocarbon alone (P<0.05). The pulmonary pathology was the mildest in the combined inhalation group, and the most severe in tetramethylpyrazine group. CONCLUSION: Combined inhalation of perfluorocarbon and tetramethylpyrazine can effectively improve the oxygenation, reduce pulmonary arterial pressure?and ameliorate lung pathology in pigs with acute lung injury.

Caffeic acid 3,4-dihydroxy-phenethyl ester induces cancer cell senescence by suppressing twist expression.

Compared with traditional cytotoxic cancer therapy, therapy-induced cancer cell senescence attracts much interest because it is similarly effective, has fewer side effects, and is more efficiently cleared by immune cells. In this study, we demonstrate that unlike caffeic acid phenethyl ester, caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE), which is isolated from the medicinal plants Sarcandra glabra and Teucrium pilosum, inhibits human cancer cell growth and colony formation by inducing cancer cell senescence, not apoptosis. CADPE induces cell senescence and morphology changes by increasing cellular size and cytoplasmic granularity, enhancing senescence-associated ß-galactosidase activity and differentiated embryo-chondrocyte expressed gene 1 expression, and blocking cell-cycle arrest in the G(1) phase. To help understand the underlying mechanisms, we show that CADPE significantly suppressed the expression of Twist1 and led to the up-regulation of rat sarcoma, p53, p21(WAF1/CIP1), and p16(INK4a) proteins in a dose-dependent manner, resulting in the hypophosphorylation of retinoblastoma protein. Furthermore, overexpression of Twist1 prevented CADPE-induced cell senescence in tumor cells. Therefore, our studies provide evidence for a novel role of CADPE in cancer cell senescence by targeting the Twist1-dependent senescence signaling pathway.

Second-sphere contributions to substrate-analogue binding in iron(III) superoxide dismutase.

A combination of spectroscopic and computational methods has been employed to explore the nature of the yellow and pink low-temperature azide adducts of iron(III) superoxide dismutase (N(3)-FeSOD), which have been known for more than two decades. Variable-temperature variable-field magnetic circular dichroism (MCD) data suggest that both species possess similar ferric centers with a single azide ligand bound, contradicting previous proposals invoking two azide ligands in the pink form. Complementary data obtained on the azide complex of the Q69E FeSOD mutant reveal that relatively minor perturbations in the metal-center environment are sufficient to produce significant spectral changes; the Q69E N(3)-FeSOD species is red in color at all temperatures. Resonance Raman (RR) spectra of the wild-type and Q69E mutant N(3)-FeSOD complexes are consistent with similar Fe-N(3) units in all three species; however, variations in energies and relative intensities of the RR features associated with this unit reveal subtle differences in (N(3)(-))-Fe(3+) bonding. To understand these differences on a quantitative level, density functional theory and semiempirical INDO/S-CI calculations have been performed on N(3)-FeSOD models. These computations support our model that a single azide ligand is present in all three N(3)-FeSOD adducts and suggest that their different appearances reflect differences in the Fe-N-N bond angle. A 10 degrees increase in the Fe-N-N bond angle is sufficient to account for the spectral differences between the yellow and pink wild-type N(3)-FeSOD species. We show that this bond angle is strongly affected by the second coordination sphere, which therefore might also play an important role in orienting incoming substrate for reaction with the FeSOD active site.