Search Results (37)

Background: Acute intermittent porphyria (AIP) is the most common and severe form of acute hepatic porphyria, caused by heterozygous mutations in the HMBS gene. Due to its non-specific clinical manifestations and low clinical awareness among clinicians, AIP is frequently misdiagnosed, leading to significant diagnostic delays and potentially fatal complications. Case presentation: We report a 20-year-old female patient who presented with a 9-month history of recurrent abdominal pain, paralytic ileus, unexplained liver injury, and hyponatremia, followed by progressive limb weakness. She was initially misdiagnosed with Guillain–Barré syndrome (GBS) and received intravenous immunoglobulin and systemic glucocorticoids. However, her condition deteriorated, and she developed life-threatening respiratory muscle paralysis requiring invasive mechanical ventilation. The diagnosis of AIP was confirmed by positive urinary porphobilinogen (PBG) testing and identification of the heterozygous HMBS c.517C>T pathogenic variant. The patient was treated with high-dose carbohydrate loading therapy and comprehensive supportive care, resulting in gradual clinical improvement. Discussion and Conclusions: This case exemplifies the substantial diagnostic challenges associated with AIP, especially when it manifests with peripheral neuropathy that closely mimics GBS. The triad of absent albuminocytologic dissociation in cerebrospinal fluid, preceding visceral symptoms, and inadequate response to standard first-line GBS therapy should immediately raise clinical suspicion for AIP. Enhanced clinical awareness of this rare disorder and timely implementation of urinary PBG screening are of paramount importance to prevent irreversible neurological complications and optimize long-term patient outcomes. Full article

Tear staining is a common yet often underestimated condition in dogs that affects appearance and may reflect underlying disease. This study evaluated dietary supplementation with the traditional Chinese herbs Chrysanthemum morifolium (CM), Cassia semen (CS), and Poria cocos (PC) in dogs predisposed to tear staining and investigated potential mechanisms. Forty Poodle and Bichon dogs were fed diets supplemented with 0.5% CM, CS, or PC. Tear staining indices were measured biweekly, together with blood indicators of iron status, immune and inflammatory markers, and antioxidant capacity. All three supplements reduced tear staining (p < 0.05), as shown by lower scores and shorter stain length versus control. CM and PC improved iron status and porphyrin metabolism by increasing serum iron and ferritin and modulating δ-aminolevulinic acid and porphobilinogen deaminase. They also enhanced humoral immunity and antioxidant status by increasing serum immunoglobulins, reducing pro-inflammatory cytokines, and moderately improving antioxidant activities. CM and PC increased fecal Allobaculum abundance, which correlated with tear staining indices and porphyrin-related measures. In conclusion, CM, CS, and PC are promising dietary strategies for reducing tear staining in dogs, with CM and PC possibly acting via Allobaculum-associated modulation of iron and porphyrin metabolism, while improving iron status, immunity, and antioxidant defense. Full article

Broccoli (Brassica oleracea var. italica) is highly nutritious, rich in vitamin C, glucosinolates, and minerals. However, its high postharvest respiratory rate leads to rapid quality deterioration, particularly chlorophyll degradation and yellowing under ambient conditions. In China, the lack of timely pre-cooling facilities exacerbates postharvest losses. Therefore, developing safe, effective and low-cost preservation methods for broccoli during transportation is of great practical importance. In this study, RNA sequencing was employed to analyze the effects of preharvest 1-methylcyclopropene (1-MCP) and postharvest pre-cooling combined with cold treatments on gene expression in broccoli. Transcriptome analysis revealed that both treatments significantly upregulated or maintained key genes involved in chlorophyll biosynthesis (e.g., Glutamyl-tRNA reductase (GluTR), porphobilinogen deaminase (PBGD), magnesium chelatase (MgCh)) and downregulated chlorophyll degradation-related genes (e.g., Chlorophyllase (CLH), pheophytinase (PPH), pheophorbide a oxygenase (PaO)), resulting in enhanced chlorophyll retention. Furthermore, chlorophyllide a oxygenase (CAO) was upregulated, while chlorophyll b reductase (CBR) was downregulated, suggesting modulation of the chlorophyll cycle. These findings elucidate the molecular mechanisms by which 1-MCP and pre-cooling combined with cold regulate chlorophyll metabolism, providing new insights into the gene regulatory network underlying the postharvest quality maintenance in broccoli. Full article

Ginseng is widely regarded as the “King of Herbs” in traditional Chinese medicine. In recent years, escalating global warming and intensified human activities have led to a continuous rise in environmental temperatures, posing a significant threat to ginseng cultivation in China. Therefore, understanding how high-temperature stress affects the photosynthetic performance of ginseng is essential for developing efficient and sustainable cultivation practices. In this study, four temperature regimes were established to systematically investigate the impact of elevated temperatures on the photosynthetic system of ginseng leaves: 25/16 °C (CK), 30/20 °C, 35/24 °C, and 40/28 °C (day/night). The results demonstrated that high-temperature stress significantly inhibited photosynthesis. Specifically, the activities of key chlorophyll biosynthesis enzymes—porphobilinogen deaminase and delta-aminolevulinate dehydratase—were markedly reduced, resulting in the accumulation of critical intermediates in the chlorophyll pathway, including protoporphyrinIX, Mg-protoporphyrinIX, and protochlorophyll. Chlorophyll synthesis was severely impaired as a result. Consequently, the contents of chlorophyll a, chlorophyll b, and carotenoids declined by 25.38%, 12.52%, and 54.63%, respectively, indicating substantial disruption of the photosynthetic pigment system. Anatomical observations revealed that high-temperatures induced stomatal closure, impairing stomata exchange and further reducing photosynthetic efficiency. Moreover, chloroplast ultrastructure was severely compromised, characterized by excessive accumulation of osmiophilic granules, disorganized and loosely stacked thylakoid membranes, and impaired capacity for light energy capture and conversion. This study provides theoretical insights into the response mechanisms of ginseng leaf photosynthesis under heat stress and establishes a scientific basis for enhancing thermotolerance through breeding programs and improved cultivation management strategies. Full article

Potato tuber (Solanum tuberosum L.) was prone to greening and quality deterioration during postharvest storage due to various factors, affecting the regulation of chlorophyll biosynthesis. In the present study, potato tubers were placed at 600 lux and 25 °C after sodium alginate—xanthan gum—glycerin composite coating. During storage, the apparent color changes and a* value of the surface were observed and determined, meanwhile the contents of nutrients, chlorophyll, and its intermediates in photosynthetic metabolism were analyzed. The results showed that after 9 d, compared to the control group, the sodium alginate coating treatment significantly inhibited greening, delayed the decline of appearance quality and nutrients including dry matter, starch, reducing sugar, soluble protein, and ascorbic acid. Furthermore, the sodium alginate coating promoted the contents of 5-aminolevulinic acid (ALA) (1.33 fold), porphobilinogen (PBG) (1.06 fold), and uroporphyrinogen III (Uro III) (1.07 fold), meanwhile, inhibited the production of protoporphyrin IX (Proto IX) (13.86%), Mg-protoporphyrin IX (Mg-Proto IX) (14.15%) and protochlorophyllide (Pchlide) (25.97%), which were key intermediates in the chlorophyll synthesis, indicating that the sodium alginate coating delay the greening by blocking the conversion of Uro III to Proto IX. These results provided valuable insights for the postharvest preservation of potato tuber. Full article

Foxtail millet is a characteristic miscellaneous grain crop with many benefits in current agricultural production and is crucial in the adjustment of the planting structure and the sustainable development of dry farming. However, the harmful effects of weeds have become a critical challenge, restricting the modern production of foxtail millet. The effect of penoxsulam on the chlorophyll metabolism pathway of foxtail millet and its physiological mechanism was studied. Spraying penoxsulam on foxtail millet leaves significantly reduced the content of chlorophyll synthesis precursors (5-aminolevulinic acid (ALA), Porphobilinogen (PBG), Protoporphyrin IX (ProtoIX), Mg-protoporphyrin IX (Mg-ProtoIX), and Protochlorophyllide (Pchlide)). Moreover, the activities of key synthetic enzymes (magnesium chelatase (MgCh) decreased compared to control, while the activities of degrading enzymes (pheophorbide a oxygenase (PAO) and pheophytinase activities (PPH) increased significantly. The study revealed the mechanism of penoxsulam inducing crop phytotoxicity by interfering with the dynamic balance of chlorophyll metabolism, which provided a theoretical basis for the scientific application of herbicides and the study of foxtail millet drug resistance. Full article

Brassinosteroids (BRs) are recognized for their ability to enhance plant salt tolerance. While considerable research has focused on their effects under neutral salt conditions, the mechanisms through which BRs regulate photosynthesis under alkaline salt stress are less well understood. This study investigates these mechanisms, examining plant growth, photosynthetic electron transport, gas exchange parameters, Calvin cycle dynamics, and the expression of key antioxidant and Calvin cycle genes under alkaline stress conditions induced by NaHCO₃. The findings indicate that NaHCO₃ stress substantially impairs cucumber growth and photosynthesis, significantly reducing chlorophyll content, net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (E), maximum photochemical efficiency (Fv/Fm), actual photochemical efficiency (ΦPSII), antenna conversion efficiency (Fv′/Fm′), and photochemical quenching coefficient (qP). This disruption suggests a severe dysregulation of the photosynthetic electron transport system, impairing electron transfer from photosystem II (PSII) to photosystem I (PSI) and subsequently the Calvin cycle. Application of exogenous 24-epibrassinolide (EBR) alleviated these effects, reducing leaf chlorosis and growth inhibition and significantly enhancing the expression of key genes within the antioxidant system (AsA-GSH cycle) and the Calvin cycle. This intervention also led to a reduction in reactive oxygen species (ROS) accumulation and improved photosynthetic performance, as evidenced by enhancements in Pn, Gs, E, Fv/Fm, ΦPSII, Fv′/Fm′, and qP. Moreover, NaHCO₃ stress hindered chlorophyll synthesis, primarily by blocking the conversion from porphobilinogen (PBG) to uroporphyrinogen III (UroIII) and by increasing chlorophyllase (Chlase) and decreasing porphobilinogen deaminase (PBGD) activity. Exogenous EBR countered these effects by enhancing PBGD activity and reducing Chlase activity, thereby increasing chlorophyll content under stress conditions. In summary, EBR markedly mitigated the adverse effects of alkaline stress on cucumber leaf photosynthesis by stabilizing the photosynthetic electron transport system, accelerating photosynthetic electron transport, and promoting the Calvin cycle. This study provides valuable insights into the regulatory roles of BRs in enhancing plant resilience to alkaline stress. Full article

Background/Objectives: Acute intermittent porphyria (AIP) is a metabolic disease characterised by neurovisceral crises with episodes of acute abdominal pain alongside life-altering, and often hidden, chronic symptoms. The elimination of precipitating factors, hemin therapy, and pain relief are strategies used to treat porphyria symptoms, but are often reserved for patients suffering recurrent, acute attacks. Givosiran (siRNA) is an emerging AIP therapy capable of silencing delta-aminolevulinic acid synthase-1 (ALAS1) and, in turn, reducing the accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) that precede porphyria symptoms. The aim of this study was to investigate the efficacy and safety of givosiran administration in patients with both acute and chronic AIP burden, who were poorly responsive to current therapies, using a personalised medicine approach. Methods: Real-world data were collected in consecutive patients treated with givosiran at an accredited German Porphyria Clinical Center. Biochemical, clinical, and HR-QoL outcomes were monitored alongside adverse events (AEs). Results: Twenty-eight patients treated between 2018 and 2024 were sub-categorised into groups corresponding to Ipnet terms 13 ‘Sporadic Attacks, 5 ‘Symptomatic High Excretors’, 5 ‘Prophylactic Heme’, and 5 “Recurrent Attacks’. The mean time from diagnosis to treatment was 9.2 years (range in months 1–324), and the mean duration of treatment was 30 months (range 3–68). After 6 months of monthly givosiran injection (2.5 mg/kg), all patients’ ALA levels reached <2ULN, and 60% of patients attained PBG levels < 2ULN (p < 0.001). These biochemical responses were not different between sub-groups (p > 0.05). Clinically, 75% of patients’ chronic and acute porphyria symptoms improved. The total patient populations’ annualised attack ratio (AAR) improved; Historical AAR: 2.9 (0–12.0) vs. Givo AAR: 0.45 (0–3.0) (p < 0.01). During follow-up, nine patients experienced minor breakthrough episodes. Of these, three patients required hemin infusion. An association between clinical success and a shorter interim period between diagnosis and treatment was evident (r = −0.522, p = 0.0061). All patients’ indices of HR-QoL improved under givosiran, including mental health (38%, p < 0.0001) and pain (38%, p < 0.0001). Patient-reported health (givosiran 77.9% vs. baseline 37.1%, p < 0.0001) and clinical outcome scores (86.9%: good–very good) were also positive. Two patients withdrew from treatment <6 months, citing fatigue, which was a common side effect. A mild elevation in liver enzymes (AST and/or ALT < 1.5ULN, 15.4%) and reduced glomerular filtration rates (GFR, 11.5%) were also evident, but no life-threatening adverse events (AEs) were attributed to givosiran treatment. Conclusions: Givosiran is effective in preventing severe acute attacks and reducing the chronic health burden in patients with acute intermittent porphyria. Importantly, HR-QoL improved in patients suffering chronic AIP burden with few incidences of historical attacks. All patients experienced substantially improved mental health, ease of living, and self-perceived health. Full article

Aminolevulinic acid (5-ALA) and dihydroporphyrin iron chelates (DHFe) play roles in plant growth regulation under normal and stressful conditions. However, definitive data on their roles in regulating chlorophyll synthesis in wheat are lacking. In this study, the optimal concentrations for foliar-spray application of 5-ALA and DHFe to promote wheat seedling growth and leaf chlorophyll content were assessed. The optimal concentrations of 5-ALA or DHFe (50 mg/L and 0.01 mg/L, respectively) were applied as foliar sprays to seedlings of wheat ‘Bainong 4199’ (high light efficient) and ‘Zhoumai No. 18’ (average light efficient) under different light intensities. Chlorophyll precursor contents and activities of three chlorophyll synthesis-related enzymes were altered, and the combined application of 5-ALA and DHFe more strongly increased the leaf chlorophyll content. 5-ALA significantly increased the contents of the chlorophyll precursors porphobilinogen, uroporphyrinogen III, protoporphyrin IX, and magnesium-protoporphyrin IX, and the activities of 5-amino-ketovalerate dehydratase and uroporphyrinogen III synthase. DHFe resulted in an increase in chlorophyll content but a significant decrease in chlorophyllase activity and protochlorophyllide content. 5-ALA promoted the synthesis of chlorophyll precursors by regulating the activities of 5-amino-ketovalerate dehydratase and uroporphyrinogen III synthase. DHFe decreased chlorophyllase activity, thereby slowing chlorophyll degradation and increasing the chlorophyll content. Full article

Salt stress is a critical abiotic factor that adversely affects plant growth and productivity by impairing photosynthesis. This study explores the impact of exogenous ascorbic acid (AsA) on the photosynthetic performance of tomato seedlings (Solanum lycopersicum L. cv. Ligeer 87-5) under salt stress. Hydroponic experiments were conducted in a solar greenhouse, where tomato seedlings were subjected to the following five treatments: Control, NaCl, NaCl + AsA, NaCl + lycorine (LYC), and NaCl + LYC + AsA. Our findings demonstrate that salt stress significantly reduced chlorophyll and carotenoid contents, levels of chlorophyll synthesis precursors (5-aminolevulinic acid (ALA), porphobilinogen (PBG), uroporphyrinogen III (Urogen III), protoporphyrin IX (Proto IX), magnesium protoporphyrin IX (Mg-Proto IX), protochlorophyllide (Pchl)), and essential elements (Mg, Fe, Mn, Zn, Mo, and P) in both roots and leaves. These reductions led to a substantial decline in net photosynthetic rate (P_n) and compromised photosystem II (PSII). In contrast, exogenous AsA application significantly enhanced the content of photosynthetic pigment precursors and essential elements, improved stomatal aperture and gas exchange efficiency, and boosted the photosynthetic performance of tomato seedlings under salt stress. Furthermore, AsA treatment mitigated the negative effects of salt stress by protecting PSII, increased light energy utilization efficiency, and alleviated both stomatal and non-stomatal limitations. The application of the AsA synthesis inhibitor LYC exacerbated the detrimental effects of salt stress, further reducing chlorophyll content and photosynthetic efficiency. In conclusion, exogenous AsA plays a vital role in enhancing the photosynthetic performance and stress tolerance of tomato seedlings under salt stress by stabilizing chlorophyll biosynthesis, facilitating essential element absorption, and optimizing stomatal function. This study provides a new approach and feasible measures for improving tomato resistance and yield, which is significant for enhancing crop productivity, managing saline soils, and promoting sustainable agricultural practices. Full article

Photodynamic therapy (PDT) treats nonmelanoma skin cancer. PDT kills cells through reactive oxygen species (ROS), generated by interaction among cellular O_2, photosensitizer and specific light. Protoporphyrin IX (PpIX) is a photosensitizer produced from methyl aminolevulinate (MAL) by heme group synthesis (HGS) pathway. In PDT-resistant cells, PDT efficacy has been improved by addition of epigallocatechin gallate (EGCG). Therefore, the aim of this work is to evaluate the effect of EGCG properties over MAL-TFD and PpIX production on A-431 cell line. EGCG’s role over cell proliferation (flow cytometry and wound healing assay) and clonogenic capability (clonogenic assay) was evaluated in A-431 cell line, while the effect of EGCG over MAL-PDT was determined by cell viability assay (MTT), PpIX and ROS detection (flow cytometry), intracellular iron quantification and gene expression of HGS enzymes (RT-qPCR). Low concentrations of EGCG (<50 µM) did not have an antiproliferative effect over A-431 cells; however, EGCG inhibited clonogenic cell capability. Furthermore, EGCG (<50 µM) improved MAL-PDT cytotoxicity, increasing PpIX and ROS levels, exerting a positive influence on PpIX synthesis, decreasing intracellular iron concentration and modifying HGS enzyme gene expression such as PGB (upregulated) and FECH (downregulated). EGCG inhibits clonogenic capability and modulates PpIX synthesis, enhancing PDT efficacy in resistant cells. Full article

Heme enzyme dysfunction causes a group of diseases called porphyrias. Particularly, a decrease in porphobilinogen deaminase, involved in the third step of heme biosynthesis, leads to acute intermittent porphyria (AIP). Considering our previous works demonstrating the multiplicity of brain metabolisms affected by porphyrinogenic agents, this study aimed to elucidate whether they cause any alteration on the mitochondrial respiratory chain. The activities of respiratory chain complexes (I to IV) were measured in encephalon mitochondria of CF1 male mice receiving volatile anesthetics: isoflurane (2 mL/kg) and sevoflurane (1.5 mL/kg), ethanol (30%), allylisopropylacetamide (AIA) (350 mg/kg), and barbital (167 mg/kg). Moreover, they were compared versus animals with pathological levels of 5-aminolevulinic acid (ALA, 40 mg/kg). Complex I–III activity was induced by isoflurane and decreased by AIA, ethanol, and ALA. Complex II–III activity was increased by sevoflurane and decreased by isoflurane and AIA. Complex II activity was increased by sevoflurane and barbital and decreased by AIA, ethanol, and ALA. Complex IV activity was increased by barbital and ALA and decreased by sevoflurane. The damage to the respiratory chain by ALA could be reflecting the pathophysiological condition of patients with AIP. Better understanding the broad effect of porphyrinogenic drugs and the mechanisms acting on the onset of AIP is vital in translational medicine. Full article

Acute intermittent porphyria (AIP) is characterized by acute neurovisceral attacks that are precipitated by the induction of hepatic 5-aminolevulinic acid synthase 1 (ALAS1). In erythropoietic protoporphyria (EPP), sun exposure leads to skin photosensitivity due to the overproduction of photoreactive porphyrins in bone marrow erythroid cells, where heme synthesis is primarily driven by the ALAS2 isozyme. Cimetidine has been suggested to be effective for the treatment of both AIP and EPP based on limited case reports. It has been proposed that cimetidine acts by inhibiting ALAS activity in liver and bone marrow for AIP and EPP, respectively, while it may also inhibit the hepatic activity of the heme catabolism enzyme, heme oxygenase (HO). Here, we show that cimetidine did not significantly modulate the activity or expression of endogenous ALAS or HO in wildtype mouse livers or bone marrow. Further, cimetidine did not effectively decrease hepatic ALAS activity or expression or plasma concentrations of the putative neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), which were all markedly elevated during an induced acute attack in an AIP mouse model. These results show that cimetidine is not an efficacious treatment for acute attacks and suggest that its potential clinical benefit for EPP is not via ALAS inhibition. Full article

Acute intermittent porphyria (AIP) is an inherited metabolic disorder associated with complications including kidney failure and hepatocellular carcinoma, probably caused by elevations in the porphyrin precursors porphobilinogen (PBG) and delta-aminolevulinic acid (ALA). This study explored differences in modern biomarkers for renal and hepatic damage between AIP patients and controls. Urine PBG testing, kidney injury panels, and liver injury panels, including both routine and modern biomarkers, were performed on plasma and urine samples from AIP cases and matched controls (50 and 48 matched pairs, respectively). Regarding the participants’ plasma, the AIP cases had elevated kidney injury marker-1 (KIM-1, p = 0.0002), fatty acid-binding protein-1 (FABP-1, p = 0.04), and α-glutathione S-transferase (α-GST, p = 0.001) compared to the matched controls. The AIP cases with high PBG had increased FABP-1 levels in their plasma and urine compared to those with low PBG. In the AIP cases, KIM-1 correlated positively with PBG, CXCL10, CCL2, and TCC, and the liver marker α-GST correlated positively with IL-13, CCL2, and CCL4 (all p < 0.05). In conclusion, KIM-1, FABP-1, and α-GST could represent potential early indicators of renal and hepatic damage in AIP, demonstrating associations with porphyrin precursors and inflammatory markers. Full article

Acute intermittent porphyria (AIP) is a metabolic disorder caused by mutations in the porphobilinogen deaminase (PBGD) gene, encoding the third enzyme of the heme synthesis pathway. Although AIP is characterized by low clinical penetrance (~1% of PBGD mutation carriers), patients with clinically stable disease report chronic symptoms and frequently show insulin resistance. This study aimed to evaluate the beneficial impact of nutritional interventions on correct carbohydrate dysfunctions in a mouse model of AIP that reproduces insulin resistance and altered glucose metabolism. The addition of spores of Bacillus coagulans in drinking water for 12 weeks modified the gut microbiome composition in AIP mice, ameliorated glucose tolerance and hyperinsulinemia, and stimulated fat disposal in adipose tissue. Lipid breakdown may be mediated by muscles burning energy and heat dissipation by brown adipose tissue, resulting in a loss of fatty tissue and improved lean/fat tissue ratio. Probiotic supplementation also improved muscle glucose uptake, as measured using Positron Emission Tomography (PET) analysis. In conclusion, these data provide a proof of concept that probiotics, as a dietary intervention in AIP, induce relevant changes in intestinal bacteria composition and improve glucose uptake and muscular energy utilization. Probiotics may offer a safe, efficient, and cost-effective option to manage people with insulin resistance associated with AIP. Full article